754 Non-conducted premature atrial complexes: a new predictor for atrial fibrillation in cryptogenic stroke patients

Aims Atrial fibrillation (AF) is the main cardiac cause of stroke, but it frequently remains undetected. In these patient monitoring for AF is recommended using a Holter electrocardiogram (ECG). The aim of the present study is to study non-conducted atrial complexes (ncPAC) recorded on Holter ECG as a new predictor of AF. Methods and results Patients admitted to the Stroke Unit of our hospital for cryptogenic stroke from December 2018 to January 2020 who underwent 24-h electrocardiographic monitoring were prospectively enrolled in the study and were subsequently submitted to 3-month and 6-month follow-up to investigate the occurrence of AF. The study recruited 112 patients. At follow-up visit, AF was diagnosed in 21.4% of the population. The only statistically significant difference between the group with and without a AF diagnosis was the presence of ncPAC (83.3% vs. 16.7%; P < 0.0001). ROC analysis was performed and showed that ncPAC had the best diagnostic accuracy in the AF diagnosis [AUC: 0.798; confidence interval (CI): 0.675–0.921]. The AUC of ncPAC was significantly better than the AUC of premature atrial complexes (PACs) (P < 0.05), CHA2DS2-VASc, HATCH, HAVOC, and C2HEST scores (P < 0.01). Kaplan–Meier curve survival estimate for AF onset by the presence of ncPAC revealed that there was a significant difference in the AF onset between patients with ncPAC and those without (P < 0.0001) and multivariate Cox-proportional hazard analysis revealed that ncPAC presence was an independent predictors of AF onset [hazards ratio (HR): 9.28; CI 95%: 2,66–32,40; P = 0.0001]. Conclusions The presence of ncPAC represents a new predictor of AF that could further guide the investigation of AF in patients with cryptogenic stroke.

545. A Retrospective Review of 30-day Mortalities in Solid-Organ Transplant Recipients (SOT) versus Non-Transplant Patients (NTP) Receiving Remdesivir (REM) and Dexamethasone (DEX) for COVID-19 Pneumonia

Background Treating COVID-19 infection in SOT is challenging due to long-term use of immunosuppressive agents. REM is the only FDA-approved anti-viral for SARS-COV-2 infection. DEX showed decrease in mortality in the Recovery Trial. COVID-19 treatment guidelines for SOT patients are the same as NTP despite limited literature on those outcomes. Our primary objective was to determine if 30-day mortality was different between SOT and NTP matched cohorts using these 2 drugs. The secondary objectives included comparisons of length of stay (LOS), days on mechanical ventilation (DMV), and the use of other treatment modalities. Methods We retrospectively collected data for hospitalized SOT and NTP, 18 years and older, with pcr-confirmed SARS-CoV-2 infection receiving REM and DEX from May 1, 2020, to October 10, 2020, at Mayo Clinic Florida. IRB approval was obtained. Descriptive statistics were used to analyze the data. Continuous variables were summarized as mean (standard deviation) or median (range) where appropriate, while categorical variables were reported as frequency (percentage). Results Of 80 patients who met the inclusion criteria, 28 were SOT, and 52 were NTP. The SOT cohort was subcategorized below: SOT patients were significantly younger than NTP (p < .001). Further, SOT patients had significantly longer LOS (p = 0.043) and more COVID-19 modalities (75% vs. 36.5%, p = 0.002) compared to NTP. Among the 28 SOT patients, 2 of them died within 30 days of admission, and among the 52 NTP patients, 7 of them died within 30 days. The 30-d survival estimate for SOT group is 92.9% (95% CI: 83.8% - 100.0%) and for NTP group is 86.5% (95% CI: 77.7% - 96.3%). The log-rank test was not significant between the groups (p=0.37), but the NTP has a worse survival curve from the figure below. SOT-NTP Survival Curve Conclusion SOT group was younger, had longer LOS, and more COVID-related modalities. The 30-d survival estimate for SOT group is 92.9% and for NTP group is 86.5%, but the survival curve for NTP was worse likely secondary to age. Use of REM & DEX in SOT recipients is a valid recommendation. Disclosures Claudia R. Libertin, MD, Gilead (Grant/Research Support)

Survival of the dysplastic hip after periacetabular osteotomy: a meta-analysis

Background: Periacetabular osteotomy (PAO) has become a popular procedure for re-orientation of the acetabulum in patients with a developmental pathomorphology. Since its first description by Reinhold Ganz in 1988, many institutions worldwide have adopted the procedure for the treatment of developmental hip dysplasia (DDH) and have subsequently reported their results. The aim of this study was to provide a meta-analysis of the likelihood of long-term survival of a dysplastic hip after PAO. Methods: A systematic literature review was conducted using Medline, Cochrane and “Web of Science” databases to identify articles reporting survival estimates for PAO in patients with DDH. To be included in the analysis, studies had to include patient cohorts aged <40 years, with Osteoarthritis grade < Tönnis III and no form of neuromuscular dysplasia. Adjustment for cohort overlap was performed. Quality assessment included level of evidence (LOE) according to the oxford center for LOE criteria and the “Methodological index for non-randomized studies (MINORS)”. After data extraction, a random-effects meta-analytical model was applied to provide weighted mean estimates of survival at 5 years, 10 years, 15 years and 20 years. Results: Nine relevant articles included 2268 dysplastic hips that underwent PAO in 9 institutions. Of the included studies, 5 presented level III evidence and 4 presented level IV evidence. The MINORS score was 11 for 3 studies, 12 for 4 studies and 13 for 2 studies. The 5-year survival after PAO was 96.1% (95% CI, 94.9–97.3), the 10-year survival was 91.3% (95% CI, 87.7–94.8), 15-year survival 85.0% (95% CI, 78.9–91.1), 20-year survival 67.6% (95% CI, 53.9–81.3). Conclusions: The results provide a representative survival estimate of a dysplastic hip after PAO based on global evidence. This should provide clinicians and patients with an adequate reflection of prognostic expectations after this kind of surgery.

Survival Outcomes Among Pancreatic Cancer Patients at Kenyatta National Hospital

Purpose: The mortality rate of pancreatic cancer varies throughout the world, with industrialized countries being hard hit. In addition, mortality has risen fast in the past two decades in Kenya and East Africa. However, there was a paucity of conclusive data about the survival of pancreatic cancer patients in the study setting. Hence, this study aimed to assess the survival outcomes of pancreatic cancer patients at Kenyatta National Hospital.Methods: A hospital-based retrospective cohort analysis was used to evaluate the survival outcomes among pancreatic cancer patients admitted in the study setting between 2015 and 2019. A total of 64 eligible pancreatic cancer patients were included in the study. In the pre-designed data abstraction tool, the data were collected by reviewing the medical records of the patients. The data were entered and analyzed using the Statistical Package for the Social Sciences version 22 software. The mean survival time was estimated using Kaplan Meier survival analysis. Cox regression analysis was employed to estimate the predictors of mortality among pancreatic cancer patients.Results: The mean age of the study participants was 60.38±12.61 years. Most of the patients had adenocarcinoma (96.9%) and were diagnosed at an advanced stage of the disease. The overall mean and median survival estimate for pancreatic cancer was 48.7±9.7 and 39.0±23.9 months, respectively. The present study showed that the overall survival rate of pancreatic cancer patients was 79.7%. Conclusion: The mortality rate of pancreatic cancer in the present was 20%. The overall mean survival estimate for pancreatic cancer was 48.7±9.7 months, and the majority had disease progression in the last follow-up period.

Association of TP53 mutation status and GATA6 amplification with clinical outcome of pancreatic cancer.

e16224 Background: Recent advances in pancreatic adenocarcinoma (PDAC) research unveiled that molecular subtypes reflect cancer prognosis and chemosensitivity. Here, we examined the possible use of genomic profiling of PDAC in the clinic by assessing retrospective clinical outcomes and treatment responsiveness based on genetic alterations. Methods: All patients treated for PDAC with Next-Generation Sequencing (NGS) data available between 2014 to 2020 at Northwell Health Cancer Institute were included in a retrospective analysis. Patients were subdivided into resectable and unresectable cancer. Genetic findings frequently reported in NGS were used to compare progression-free survival (PFS) and overall survival (OS) within subgroups. Survival probability was compared using Peto-Peto’s modified survival estimate followed by pairwise comparisons using Peto-Peto’s modified survival estimate. Family-wise error rate was adjusted using Benjamini & Hochberg method. Results: A total 115 patients were qualified for the evaluation. In all cases of PDAC, TP53 mutation (n = 89) was associated with poor OS compared to the wild-type TP53 gene (n = 19) (median OS 20.2 months, 95% CI 10.2 to 39.7, vs. 41.1 months, 95% CI 20.9 to 81.0, HR 1.98, p = 0.028). In unresectable PDAC, tumors with GATA6 amplification (n = 11) were associated with a significantly better OS over patients whose tumors harbored a TP53 mutation (n = 57) (median OS 22.9 months, 95% CI 9.6 to 54.5, vs. 10.0 months, 95% CI 4.2 to 23.8, HR 0.48, p = 0.048) . Within the TP53 mutation group, FOLFIRINOX (n = 21) did not show improved OS compare to Gem/NabP (n = 30) (mean OS 13.8 months, 95% CI 6.8 to 28.2, vs. 8.5 months, 95% CI 4.17 to 17.4, HR 0.84, p = 0.25). Other genetic alterations were not associated with OS. There was no difference in PFS in all PDACs. Conclusions: Our retrospective analysis showed that genetic changes in TP53 and GATA6 were significantly associated with the clinical outcome for PDAC. Mutation of TP53 was associated with poor OS in general. However, in unresectable PDAC, GATA6 amplification was associated with better clinical outcome than tumors with TP53 mutation. In contrary to general belief, FOLFIRINOX did not result in better OS than Gem/NabP.

High density and survival of a native small carnivore, the Florida spotted skunk (Spilogale putorius ambarvalis), in south-central Florida

The eastern spotted skunk (Spilogale putorius) is a species of conservation concern across much of its range and has experienced a population decline since the 1940s. Little is known about the Florida spotted skunk (S. p. ambarvalis), a subspecies endemic to peninsular Florida, but previous studies and the frequency of incidental observations suggest that populations of this subspecies might be more abundant than the two eastern spotted skunk subspecies that occur elsewhere. To better understand the status and demography of the Florida spotted skunk, we assessed the density and survival of a population occurring predominantly in dry prairie habitat in south-central Florida. To obtain density estimates, we trapped spotted skunks on a mark–recapture grid over 11 independent 4-day trapping sessions from 2016 to 2018. To obtain survival estimates, we monitored weekly survival of 38 radiocollared spotted skunks (20 collared initially in 2016 and 18 collared initially in 2017) from February 2016 to August 2017. We captured a minimum of 91 unique spotted skunks on 404 occasions on the mark–recapture grid and our density estimates ranged from 6.52 ± 2.93 skunks/km2 to 23.29 ± 7.65 skunks/km2, depending on trapping session, but seasonal differences in density were not significant. The sex ratio of spotted skunks at our site was 1.0M:3.8F. Mean annual survival for all spotted skunks was 0.714 (0.503–0.925, 95% CI), and sex, season, and year did not have significant effects on survival. This survival estimate is the highest reported thus far for any skunk species. Collectively, the density and survival estimates from our study are higher than those of many other mephitids and mustelids of similar size, and these findings reinforce the value of studying locally abundant populations of small carnivores to better inform the conservation, management, and potential restoration of these species in the future.

Phase I Study of Ixazomib Added to Chemotherapy in the Treatment of Acute Lymphoblastic Leukemia in Older Adults

Introduction: While progress has been made in the treatment of childhood leukemia, the outlook for patients &gt;60 years of age with acute lymphoblastic leukemia (ALL) is poor with complete remission rates (CR) of approximately 60% and 3-year survivals (OS) of less than 15%. Intensified treatment in a later CALGB trial showed little improvement with a CR=61% and 5-year OS=6% (Stock, Cancer 2013). Ixazomib is an oral proteasome inhibitor, which has shown single agent activity and promising combination activity in pediatric ALL patients (Messinger, Blood 2012). We sought to assess the safety and tolerability, as well as early efficacy of adding ixazomib to a current MGH-DFCI/HCC multi-agent regimen for older adults with ALL. Methods: Patients aged 51 to 75 years of age with newly diagnosed B-ALL and T-ALL were screened for eligibility. Patients with mature ALL (including Burkitt's) were excluded. Patients with Philadelphia chromosome positive ALL (BCR-ABL1+) were eligible, and dasatinib was added to the chemotherapy on Day 10 for these patients. The chemotherapy treatment schedule from induction through maintenance is outlined in Table 1. A standard 3 + 3 patient cohort dose escalation design was used to determine the maximum tolerated dose (MTD) of ixazomib during induction for these patients, the primary objective of the trial. After consolidation I, patients in complete remission (CR) with a suitable donor were offered a hematopoietic stem cell transplantation (HSCT) as per institutional guidelines. Those not going to HSCT continued therapy as noted in the table. Results: There were 19 patients with B-ALL enrolled, none with T-ALL. Among these patients, 7 harbored BCR-ABL1 rearrangements. The median age was 65 years, 74% were male, and 90% had a performance status 0 or 1. The MTD was 2.3 mg of ixazomib, as 2 patients at 3.0 mg developed DLT's: a grade 3 peripheral neuropathy and a grade 5 acute kidney injury (Table 2). Grade 3 and 4 toxicities encountered at any time consisted mainly of grade 4 neutropenia in 13 patients and grade 4 thrombocytopenia in 12 patients. One patient experienced grade 3 neutropenia and 5 patients experienced grade 3 thrombocytopenia. Two patients with grade 2 neuropathy did not meet the definition of DLT. Among the 19 patients, 15 (79%, [95% confidence interval (CI), 54-94%]) achieved CR (14) or CRi (1), and 5 patients went on to HSCT. The median follow-up time was 2 years (range, 1-5) for 8 patients remaining alive. The 1-year overall survival estimate was 53% [95% CI, 29-72%], while the 2-year overall survival estimate was 47% [95% CI, 24-67%]. Conclusions: A dose of 2.3 mg of ixazomib in combination with induction chemotherapy among older patients with ALL was well-tolerated and associated with a promising rate of complete remission. Disclosures Amrein: Takeda: Research Funding; AstraZeneca: Consultancy, Research Funding; Amgen: Research Funding. Brunner:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; AstraZeneca: Research Funding; Forty-Seven Inc: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding. Hobbs:Novartis: Honoraria; Celgene/BMS: Honoraria; Jazz: Honoraria; Constellation: Honoraria, Research Funding; Incyte: Research Funding; Merck: Research Funding; Bayer: Research Funding. Neuberg:Celgene: Research Funding; Pharmacyclics: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company. Fathi:Takeda: Consultancy, Research Funding; Agios: Consultancy, Research Funding; PTC Therapeutics: Consultancy; Amphivena: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Newlink Genetics: Consultancy; Pfizer: Consultancy; Blueprint: Consultancy; Trillium: Consultancy; Kura Oncology: Consultancy; Forty Seven: Consultancy; Jazz: Consultancy; Boston Biomedical: Consultancy; BMS/Celgene: Consultancy, Research Funding; Kite: Consultancy; Trovagene: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy, Research Funding; Abbvie: Consultancy. OffLabel Disclosure: MLN 9708, ixazomib is FDA approved for multiple myeloma. In this trial it is used to treat acute lymphoblastic leukemia.

Long-Term Results of the RAPCO Trials

Background: An internal thoracic artery graft to the left anterior descending artery is standard in coronary bypass surgery, but controversy exists on the best second conduit. The RAPCO trials (Radial Artery Patency and Clinical Outcomes) were designed to compare the long-term patency of the radial artery (RA) with that of the right internal thoracic artery (RITA) and the saphenous vein (SV). Methods: In RAPCO-RITA (the RITA versus RA arm of the RAPCO trial), 394 patients <70 years of age (or <60 years of age if they had diabetes mellitus) were randomized to receive RA or free RITA graft on the second most important coronary target. In RAPCO-SV (the SV versus RA arm of the RAPCO trial), 225 patients ≥70 years of age (or ≥60 years of age if they had diabetes mellitus) were randomized to receive RA or SV graft. The primary outcome was 10-year graft failure. Long-term mortality was a nonpowered coprimary end point. The main analysis was by intention to treat. Results: In the RA versus RITA comparison, the estimated 10-year patency was 89% for RA versus 80% for free RITA (hazard ratio for graft failure, 0.45 [95% CI, 0.23–0.88]). Ten-year patient survival estimate was 90.9% in the RA arm versus 83.7% in the RITA arm (hazard ratio for mortality, 0.53 [95% CI, 0.30–0.95]). In the RA versus SV comparison, the estimated 10-year patency was 85% for the RA versus 71% for the SV (hazard ratio for graft failure, 0.40 [95% CI, 0.15–1.00]), and 10-year patient survival estimate was 72.6% for the RA group versus 65.2% for the SV group (hazard ratio for mortality, 0.76 [95% CI, 0.47–1.22]). Conclusions: The 10-year patency rate of the RA is significantly higher than that of the free RITA and better than that of the SV. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00475488.

Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: Phase Ib results.

7507 Background: Magrolimab (Hu5F9-G4) is an antibody blocking CD47, a macrophage immune checkpoint and don’t eat me signal on cancers. It induces tumor phagocytosis and eliminates leukemia stem cells. Azacitidine (AZA) synergizes with magrolimab by inducing eat me signals on leukemic cells, enhancing phagocytosis. We report Ph1b data including a potential MDS registration cohort. Methods: Magrolimab+AZA was given to untreated intermediate to very high risk IPSS-R MDS and intensive chemo unfit AML patients. A magrolimab priming/intrapatient dose escalation regimen (1-30 mg/kg QW, Q2W Cycle 3+) was used. AZA was dosed 75mg/m2 days 1-7. Efficacy was assessed by IWG 2006 (MDS) and ELN 2017 (AML) criteria. Results: 68 patients (39 MDS, 29 AML) with a median age of 72 were treated with magrolimab+AZA. 19% were intermediate cytogenetic risk with 68% poor risk (13% unknown). 27% were TP53 mutant. The combo was well-tolerated with safety similar to AZA alone. Common treatment-related AEs were anemia (38%), fatigue (21%), neutropenia (19%), thrombocytopenia (18%) and infusion reaction (16%). Treatment-related febrile neutropenia was 1.5%. Only 1 patient (1.5%) discontinued due to an AE. In RBC transfusion dependent patients, 58% of MDS and 64% of AML patients became transfusion independent. 30/33 (91%) efficacy evaluable MDS patients had an objective response (42% CR, 24% marrow CR (4/8 also with HI), 3% PR, 21% HI alone, 9% SD). MDS patient responses deepened on study, with a 56% CR rate in patients with ≥ 6 mo follow-up. In AML, 16/25 (64%) responded (40% CR, 16% CRi, 4% PR, 4% MFLS, 32% SD, 4% PD). In 12 TP53 mutant AML patients, 75% had a CR+CRi (42% CR, 33% CRi, 17% SD, 8% PD). Cytogenetic CR was seen in 35% and 50% of responding MDS and AML patients. 22% of MDS and 50% of AML patients with CR/CRi/marrow CR were MRD negative by flow cytometry. Median duration of response is not reached in either MDS or AML, including TP53 mutant AML, with a median follow-up of 5.8, 8.8 and 9.4 mos, respectively (range: 1.9 – 16.8 mos). 91% of MDS and 100% of AML responding patients are in response at 6 mos. The 6 mo overall survival estimate is 100% in MDS and 91% in TP53 mutant AML patients. Conclusions: Magrolimab is a macrophage targeting immunotherapy that with AZA is well tolerated with durable efficacy in MDS, AML, particularly TP53 mutant, a poor prognostic group. A potential registration single arm MDS cohort is ongoing (NCT03248479). ENHANCE, a randomized Ph3 MDS trial is planned. Additional patients/analyses will be reported. Funded by Forty Seven and CIRM. Clinical trial information: NCT03248479 .