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Abstract Background Periprocedural myocardial infarction (PMI) occurs frequently after both percutaneous coronary intervention (PCI) and bypass grafting surgery (CABG) in patients with complex coronary artery disease (CAD), and PMI has been shown to have a detrimental impact on mortality. On the other hand, long-term impact of PMI on mortality has not been fully evaluated. Purpose This study aimed to assess the impact of PMI according to SCAI definition on 10-year all-cause death in patients with complex CAD. Methods The SYNTAX Extended Survival (SYNTAXES) study evaluated vital status up to 10 years in 1800 patients with de novo three-vessel disease and/or left main coronary artery disease randomized to treatment with CABG or PCI in the SYNTAX trial. Blood was sampled for creatine kinase (CK) pre- and post-revascularisation, and the cardiac specific MB iso-enzyme (CK-MB) was determined only if the CK ratio ≥2 x the upper limit of normal (ULN). If the CK ratio <2 ULN, CK-MB assessment was not mandated. In this analysis, patients with at least one blood sampling within 48 hours of the procedure were included. PMI was defined as follows; peak CK-MB measured within 48 hours of the procedure ≥10 x ULN, or ≥5 x ULN with new Q-waves in 2 contiguous leads or new persistent left bundle branch block. Results Of 1800 patients, 1679 (93.2%) patients were included. Of 877 patients treated with PCI, PMI occurred in 26 patients (3.0%), whereas 14 (1.7%) PMIs were observed in 802 patients treated with CABG. Compared with patients without PMI, patients with PMI presented with unstable angina more frequently (45.0% vs. 28.7, p=0.033), and had a higher rate of bifurcation lesion (87.5% vs. 72.5, p=0.046). PMI was associated with a higher all-cause mortality at 10 years compared with no PMI (55.3% vs. 25.4%; Log-rank p<0.001, Figure), which was mainly driven by a high mortality rate within 1 year. In patients undergoing PCI, the mortality rates were significantly higher in patients with PMI not only within 1 year (Log-rank p<0.001) but also beyond one year (Log-rank p=0.016), compare to patients without PMI (Figure). On the other hand, in patients undergoing CABG, a higher mortality rate in patients with PMI was observed until 1 year (Log-rank p<0.001), but the impact of PMI on mortality beyond one year after CABG subsided (Log-rank p=0.308) (Figure 1). Conclusion PMI was associated with a poor prognosis at 10 years. The impact of PMI on mortality was strong within one year. Of note, the impact of PMI on mortality persisted beyond 1 year only in patients undergoing PCI. Patients who were treated with PCI and suffered PMI need careful follow-up beyond one year after revascularization. Figure 1 Funding Acknowledgement Type of funding source: None

Abstract ObjectiveChondrocyte apoptosis plays a vital role in osteoarthritis (OA) progression. Angelica sinensis polysaccharide (ASP), a traditional Chinese medicine, possesses anti-inflammatory and anti-apoptotic properties in chondrocytes. This study aimed to determine the protective role of ASP on sodium nitroprusside (SNP)-induced chondrocyte apoptosis, and explore the underlying mechanism.MethodHuman primary chondrocytes isolated from articular cartilage of OA patients were treated with SNP alone or in combination with different doses of ASP. Cell viability and apoptosis were assessed, and apoptosis-related proteins including Bcl-2 and Bax were detected. Autophagy levels were evaluated by light chain 3 (LC3)-II immunofluorescence staining, mRFP-GFP-LC3 fluorescence localisation and western blot (LC3II, p62, Beclin-1, Atg5). Meanwhile，activation of ERK 1/2 pathway was determined by western blot. The autophagy inhibitors 3-Methyladenine (3-MA), chloroquine (CQ) and a specific inhibitor of ERK1/2, SCH772984, were used respectively to confirm the autophagic effect of ASP.ResultsThe results showed that SNP-induced chondrocyte apoptosis was significantly rescued by ASP, whereas ASP alone promoted chondrocytes proliferation. The anti-apoptotic effect of ASP was related to the enhanced autophagy and depended on the activation of ERK1/2 pathway.ConclusionASP markedly rescued SNP-induced chondrocyte apoptosis by activating ERK1/2-dependent autophagy in chondrocytes, and it made ASP a potential therapeutic supplementation for OA treatment.

Background: With the incorporation of positron emission tomography (PET) imaging as part of the standard staging evaluation of follicular lymphoma (FL), it is generally recommended to obtain the diagnostic biopsy from a lesion with the highest standardized uptake value (SUV) to rule out de novo histologic transformation (HT). In some cases such an approach might be impractical, while in other cases a biopsy from a diseased area with a high SUV may still demonstrate an indolent histology. To date, there is no data to guide treatment choices in patients (pts) with FL with high SUVmax but with no documented evidence of HT. Specifically, it remains unclear whether anthracycline-containing regimens, such as R-CHOP, provide a better outcome than R-Bendamustine (BR). Furthermore, it is unknown whether rituximab (R) maintenance is beneficial in this setting. Therefore, we aimed to compare the efficacy of R-CHOP vs BR in newly diagnosed FL pts with high SUVmax at baseline PET and to clarify the role of maintenance. Patients and Methods: We retrospectively identified 261 consecutive pts with newly diagnosed biopsy-proven FL1-3A and a SUVmax≥13 on baseline PET, who were treated with frontline R-CHOP (n=183) or BR (n=78) at 7 US cancer centers based on the physician's choice. Progression-free survival (PFS) was calculated from starting treatment until progression, relapse or death. Cut-offs of SUVmax ≥13≤18 and SUVmax>18 were used for sub-analysis (Haematologica;2020;105:1907-1913). Results: Median age was 59 years. The baseline characteristics of the two groups differed significantly for a younger age (58 vs 62 years, p=0.009), a higher rate of B-symptoms (26% vs 10%, p=0.005) and baseline SUVmax>18 (49% vs 36%, p=0.04) in the R-CHOP group. A diagnostic biopsy was obtained from the site at the highest SUV in 129 (71%) and 43 (55%) pts, respectively (p=0.01). These suggest a potential selection of R-CHOP in pts with adverse features. At the end of therapy (EoT), R-CHOP treated pts achieved higher PET-CT complete response rates (CR 82% vs 69%, p=0.02). This superiority held in pts with diagnostic biopsy at the highest SUV site (CR 83% vs 67%, p=0.03), but not in the others (CR 80% vs 71%, p=0.37). Progression occurred at EoT in 11 and 14 pts receiving R-CHOP and BR (6% vs 18%, p=0.02), with a higher rate of HT in the BR group (13% vs 4%, p=0.006). After a median follow-up of 76 months (range, 4-208 months), there was no significant difference in PFS between R-CHOP and BR treated pts (hazard ratio [HR] 1.22, p=0.34). PFS was strongly associated with FLIPI 2 (HR 2.32, p=0.01) and 3-5 (HR 2.69, p=0.003) in the univariate as well as in the multivariate analysis (FLIPI 2 HR 2.19, p=0.02; FLIPI 3-5 HR 2.51, p=0.01). There was a trend toward overall survival (OS) benefit in the R-CHOP group (Fig.1A). In the univariate analysis for OS, BR regimen (HR 2.12, p=0.03), age >60 (HR 2.54, p=0.006), FLIPI 3-5 (HR 5.13, p=0.03) and biopsy at the highest SUV site (HR 0.44, p=0.01) were prognostic, however none of those remained significant in the multivariate analysis (BR regimen HR 1.84, p=0.09; age >60 HR 1.92, p=0.08; FLIPI 3-5 HR 3.11, p=0.14; biopsy at the highest SUV site HR 0.60, p=0.13; SUVmax>18 HR 1.87, p=0.055). Among pts with EoT response after R-CHOP or BR (n=170 and n=64, respectively), one third in each group (36% vs 41%, respectively) received R-maintenance for a median of 8 administrations (range, 2-12). A significant PFS advantage (landmark analysis) was observed with R-maintenance (Fig.1B; HR 0.53, p=0.02); however, this did not translate in survival benefit (HR 0.67, p=0.49). In a multivariable model, R-maintenance (HR 0.53, p=0.02), FLIPI 2 (HR 2.47, p=0.03) and 3-5 (HR 2.79, p=0.01) remained independent prognosticators of PFS, while no parameters significantly affected OS. The 2-year HT rate (10% vs 17%) and cumulative incidence did not statistically differ between R-CHOP and BR groups (Fig.1C, p=0.159). Early progression (POD24) occurred in 43 and 22 pts who received R-CHOP and BR, respectively (24% vs 28%) and resulted in a significantly higher risk of death (HR 4.12, p=0.006). Conclusion: In newly diagnosed FL pts with SUVmax≥13 at baseline PET, R-CHOP was more effective in achieving CR and reducing the risk of early HT compared with BR, and it was associated with a trend toward survival advantage. Rituximab maintenance significantly prolonged PFS. A prospective evaluation with a larger population will be needed to confirm our findings. Disclosures Joffe: Epizyme: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Ruella:Abclon, BMS, NanoString: Consultancy; Abclon: Consultancy, Research Funding; UPenn/Novartis: Patents & Royalties. Svoboda:Adaptive: Consultancy; Astra-Zeneca: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Imbrium: Consultancy; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Research Funding; TG: Research Funding; Genmab: Consultancy; Atara: Consultancy. Witzig:Immune Design: Research Funding; Spectrum: Consultancy; Karyopharm Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Consultancy, Research Funding; AbbVie: Consultancy; MorphSys: Consultancy; Incyte: Consultancy. Smith:TG Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy; Celgene: Consultancy, Research Funding; Pharmacyclics: Research Funding; Karyopharm: Consultancy, Research Funding; FortySeven: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding. Armand:Affimed: Consultancy, Research Funding; Otsuka: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; IGM: Research Funding; Infinity: Consultancy; Genentech: Research Funding; Sigma Tau: Research Funding; Celgene: Consultancy; Adaptive: Consultancy, Research Funding; Tensha: Research Funding; Roche: Research Funding; Merck & Co., Inc.: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy. Nastoupil:Janssen: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Gilead/KITE: Honoraria; Gamida Cell: Honoraria; TG Therapeutics: Honoraria, Research Funding; Merck: Research Funding; Novartis: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Ansell:Takeda: Research Funding; Regeneron: Research Funding; Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; AI Therapeutics: Research Funding; ADC Therapeutics: Research Funding. Zelenetz:Novartis: Consultancy; Adaptive Biotechnology: Consultancy; Genentech/Roche: Consultancy; Gilead: Consultancy; Gilead: Research Funding; Celgene: Consultancy; Roche: Research Funding; Amgen: Consultancy; BeiGene: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Sandoz: Research Funding; Celgene: Research Funding; MorphoSys: Research Funding; MEI Pharma: Research Funding. Younes:BioPath, Xynomic, Epizyme, and F. Hoffmann-La Roche: Consultancy; Janssen, Curis, Merck, Bristol-Myers Squibb, Syndax Pharmaceuticals, F. Hoffmann-La Roche, Curis (Inst), Johnson & Johnson (Inst), Novartis (Inst): Research Funding; Janssen, AbbVie, Merck, Curis, Epizyme, F. Hoffmann-La Roche, Takeda, Bristol-Myers Squibb, Bayer HealthCare Pharmaceuticals, Celgene, Incyte, Janssen Pharmaceuticals, Merck, Sanofi, Seattle Genetics, Takeda Millennium: Honoraria; AstraZeneca: Current Employment; MSKCC: Ended employment in the past 24 months.

Abstract To evaluate the racial and ethnic differences in prevalence of germline pathogenic variants (PVs) and the effect of race and ethnicity on breast cancer (BC) risk among carriers, results of multigene testing of 77 900 women with BC (non-Hispanic White [NHW] = 57 003; Ashkenazi-Jewish = 4798; Black = 6722; Hispanic = 5194; and Asian = 4183) were analyzed, and the frequency of PVs in each gene were compared between BC patients (cases) and race- and ethnicity-matched gnomAD reference controls. Compared with NHWs, BRCA1 PVs were enriched in Ashkenazi-Jews and Hispanics, whereas CHEK2 PVs were statistically significantly lower in Blacks, Hispanics, and Asians (all 2-sided P < .05). In case-control studies, BARD1 PVs were associated with high risks (odds ratio > 4.00) of BC in Blacks, Hispanics, and Asians; ATM PVs were associated with increased risk of BC among all races and ethnicities except Asians, whereas CHEK2 and BRIP1 PVs were associated with increased risk of BC among NHWs and Hispanics only. These findings suggest a need for personalized management of BC risk in PV carriers based on race and ethnicity.

AbstractIntroductionThe right ventricle (RV) strain measured by speckle tracking (RVS) is an echocardiographic parameter used to assess RV function. We compared RVS to RV fractional area change (FAC%), tricuspid annular plane systolic excursion (TAPSE) and Doppler tissue imaging‐derived peak systolic velocity (Sʹ) in the assessment of right ventricular (RV) systolic function measured using cardiac magnetic resonance imaging (MRI).MethodsWe enrolled consecutive patients who underwent cardiac MRI between Jan 2012 and Dec 2017 and a transthoracic echocardiogram (TTE) within 1 month of the MRI with no interval event. Baseline clinical characteristics and MRI parameters were extracted from chart review. Echocardiographic parameters were measured prospectively. TTE parameters including RVS, TAPSE, Sʹ, and FAC% were tested for accuracy to identify impaired RV EF (EF < 45% & <30%) using receiver operator curves.ResultsThe study cohort included 500 patients with mean age 55 years ± 18 and peak tricuspid regurgitation velocity 2.7 ± 1.4 m/s. The area under ROC for RVS was 0.69 (95% CI 0.63–0.75) and 0.78 (95% CI 0.70–0.88) to predict RVEF < 45% & RVEF < 30%, respectively. The RV FAC% had second highest accuracy of predicting RVEF among all the TTE parameters tested in study.ConclusionRight ventricular strain is the most accurate echocardiographic method to detect impaired right ventricular systolic function when using MRI as the gold standard.

PurposeIn quantitative susceptibility mapping (QSM) using magnetic resonance imaging, image reconstruction methods usually aim at suppressing streaking artifacts. In this study, a streaking detection method is proposed for evaluating and optimizing quantitative susceptibility maps.MethodsNine healthy subjects participated in this study and underwent three‐dimensional multi‐echo gradient echo scans. Regularized iterative algorithm was used for reconstruction of tissue susceptibility maps in all subjects. Streaking detection was applied to evaluate streaking artifact in tissue susceptibility maps. In addition, an optimization process for QSM reconstruction by streaking detection was applied and was compared with matching noise level method.ResultsIt is shown that the proposed streaking detection technique effectively delineates streaking artifact in tissue susceptibility maps. In QSM reconstruction, optimization by streaking detection successfully determines the regularization factor that balances between streaking artifact suppression and tissue texture preservation. ROI analyses of brain tissue susceptibility show that optimization by streaking detection achieves results in good agreement with that from matching noise level method.ConclusionsStreaking detection enables direct visualization of streaking patterns in tissue susceptibility maps. It can be applied both for evaluating QSM reconstruction quality and for comparing different reconstruction algorithms. Furthermore, streaking detection can be incorporated into an optimization process of QSM reconstruction. Therefore, we conclude that the proposed method will add value to reconstruction of QSM.

AbstractA previously healthy 49‐year‐old male patient presented with COVID‐19 infection and required mechanical ventilation and extracorporeal membrane oxygenation due to severe hypoxemia. Echocardiography showed cardiac dysfunction with an apical sparing strain pattern, which rapidly normalized within a week. Apical sparing myocardial strain in patients with COVID‐19 infection may suggest reverse‐type stress cardiomyopathy.