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Abstract INTRODUCTION Dendritic cells (DCs) are potent antigen presenting cells that can be exploited to initiate an adaptive anti-tumoral immune response. DC vaccine clinical trials for primary glioblastoma (GBM) have reported prolonged progression-free survival without any impact on overall survival (OS). We report a radiomics approach that identifies a subpopulation of patients with prolonged OS in clinical trial MC1272. METHODS Twenty adults with primary GBM undergoing standard-of-care therapy were enrolled in MC1272. Autologous DCs were pulsed with allogenic GBM cell lines to generate vaccines that were administered for up to twelve cycles. Standard brain imaging was obtained at the initiation of treatment and two months afterwards. An independent cohort of image-localized biopsies underwent RNA sequencing followed by cellular deconvolution to estimate T cell abundance. A machine learning model was trained to predict intratumoral T cell abundance from imaging features, and the model was applied to MC1272 patient imaging. RESULTS Voxelwise predictions of T cell abundance were generated for each patient’s pre- and post-treatment images. The difference in total intratumoral T cell abundance between imaging timepoints classified patients into increasing or decreasing T cell groups. Patients whose T cells increased had longer OS (median, 21 months) than those whose T cells decreased (median, 10 months; p=0.0035). The significance remained in a Cox proportional hazards analysis that adjusted for patient age and sex (p=0.011). CONCLUSIONS A spatially-resolved radiomics model detected that an intratumoral T cell influx after DC vaccine therapy was associated with prolonged OS. The “post-treatment” imaging in this study was obtained a mere two months after DC vaccine initiation, suggesting that our radiomics model can provide an early indication of treatment responsiveness and prognosis in these patients.

Introduction: Pulmonary embolism (PE) is an uncommon medical complication after stroke. Predisposing factors include deep vein thrombosis (DVT) in patients with hemiplegia or an underlying hypercoagulable state. However, little information is known regarding PE in stroke patients. Objective: We evaluated clinical characteristics, predisposing factors, and outcomes in stroke patients who developed PE. Methods: We included patients with an acute ischemic stroke (AIS) admitted to the participating institutions in the Registry of the Canadian Stroke Network between 2003 to 2008. Pulmonary embolism was diagnosed by nuclear imaging within 30 days of the stroke case index. Demographic data and clinical variables were collected. Logistic regression and survival analyses were completed to determine the association of risk factors with the outcomes of interest. Outcome Measures: primary outcome was death or disability at discharge defined as the modified Rankin scale >3. Secondary outcomes include admission to the Intensive Care Unit, disposition, and length of hospital stay, death at 3 months and at 1 year. Results: Among 11,287 patients with AIS, PE was found in 89 (0.78%) of patients. The development of PE was associated with higher risk of death in 30 days (25.8%vs 13.6%;p <0.001) and 1 year, (47.2% vs 24.6%;p <0.001). Disability was also more common in stroke patients with PE (85.4% vs 63.6% without PE; p <0.001). Mean length of stay was longer in stroke patients with PE (36 vs 16 days; p<0.001). Past medical history of cancer or deep vein thrombosis, history of cardiac arrest or deep vein thrombosis during admission were associated with PE. After adjustment, PE was associated with lower survival at 30 days (p value = 0.0012) and 1 year (p value < 0.0001) (Figures 1 & 2 represent survival function). Conclusions: In this large study, PE occurs in approximately 1% of AIS patients. PE was associated with higher disability, longer length of stay and lower short and long-term survival.

SummaryBackgroundObesity may affect efficacy and safety of biologic treatments for ulcerative colitis (UC). Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC.AimsTo assess efficacy and safety of tofacitinib in patients with UC, by baseline body mass index (BMI).MethodsThis post hoc analysis evaluated patients with UC receiving placebo or tofacitinib from the 8‐week OCTAVE Induction 1 and 2 (NCT01465763, NCT01458951) and 52‐week OCTAVE Sustain (NCT01458574) studies. Patients were stratified by BMI at OCTAVE Induction 1 and 2 baseline (<25, 25 to <30 and ≥30 kg/m2). Outcomes included remission, endoscopic improvement, clinical response, sustained steroid‐free remission, Inflammatory Bowel Disease Questionnaire total score and Short Form‐36 Health Survey scores. Adverse events were evaluated.ResultsAt Week 8 of OCTAVE Induction 1 and 2, and Week 52 of OCTAVE Sustain, higher proportions of patients receiving tofacitinib 5 or 10 mg twice daily (b.d.) achieved clinical response vs placebo, regardless of baseline BMI subgroup (all P < 0.05). Proportions of patients achieving efficacy endpoints were generally similar across BMI subgroups; in univariate and multivariate regression analyses, BMI was not a significant predictor (all P ≥ 0.05; univariate BMI [continuous] odds ratio for remission: 0.98 [95% confidence interval 0.95, 1.02]). There was no consistent trend between BMI and adverse events. Among patients receiving tofacitinib 10 mg b.d. in OCTAVE Induction 1 and 2, serious infections were numerically greater in the BMI ≥30 subgroup (3.2%) vs other subgroups (0.4%). Limitations included small patient numbers in the BMI ≥30 subgroup.ConclusionsEfficacy and safety of tofacitinib were similar in patients with UC regardless of baseline BMI.

Objective: The aim of this study was to investigate the midterm outcomes of fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal (PRA) and thoracoabdominal aortic aneurysms (TAAAs). Summary Background Data: FB-EVAR has been associated with decreased morbidity compared to open repair, but there is limited midterm data. Methods: A total of 430 patients (302 males, mean age 74 ± 8 years) treated by FB-EVAR were enrolled in a prospective, nonrandomized investigational device exemption study. Endpoints included 30-day mortality and major adverse events (MAEs), freedom from all cause and aortic-related mortality, target vessel patency, and freedom from secondary intervention and target vessel instability. Results: There were 133 PRAs and 297 TAAAs with 1673 renal-mesenteric arteries incorporated by fenestrations or directional branches (3.9 ± 0.5 vessels/patient). At 30 days or within the hospital stay if longer than 30 days, there were 4 (0.9%) deaths. MAEs included new-onset dialysis in 8 patients (2%), permanent paraplegia or stroke in 10 patients each (2%), and respiratory failure requiring tracheostomy in 2 patients (0.5%). After a mean follow-up of 26 ± 20 months, there were 3 (0.7%) aortic-related deaths from SMA stent occlusion, gastrointestinal hemorrhage, or complications of open arch repair. At 5 years, freedom from all-cause and aortic-related mortality were 57% ± 5% and 98% ± 1%, respectively. Freedom from secondary intervention was 64% ± 4%, primary target vessel patency was 94% ± 1%, and freedom from target vessel instability was 89% ± 2% at same interval. One patient (0.2%) had nonfatal aneurysm treated using endovascular repair. Conclusion: FB-EVAR is safe and effective for treatment of PRA and TAAAs with low rate of aortic-related mortality and aneurysm rupture on midterm follow-up.

In the renal proximal tubule (PT), Na + /K + ‐ATPase (NKA) is exclusively located in the basolateral domain. Through its classic ATP‐dependent ion‐pumping function, NKA generates the Na + gradient that drives apical Na + reabsorption, mostly through Na + /H + exchanger (NHE3). Accordingly, activation of NKA‐mediated ion transport decreases natriuresis through activation of basolateral (NKA) and apical Na + reabsorption (NHE3). In contrast, pharmacological evidence suggests that activation of the more recently discovered NKA signaling function triggers a cellular redistribution of NKA and NHE3 that decreases transcellular Na + flux in cultured PT cells. To obtain genetic evidence of this NKA/Src mechanism in the PT and asses its physiological importance, we used a knockdown and rescue approach in pig renal epithelial cells (LLC‐PK1). Additionally, we genetically targeted NKA α1 in the mouse PT by crossing mice expressing a sodium glucose co‐transporter 2 promoter driven Cre transgene with Floxed NKA α1 mice (PTα1 ‐/‐ ). Knockdown of 90% of NKA α1 in PT LLC‐PK1 cells increased transepithelial 22 Na flux by 2‐fold, activated NHE3 (50% decrease in inhibitory phosphorylation), and increased basolateral Na + /HCO 3 ‐ cotransporter (NBCe1A) protein content. In the PTα1 ‐/‐ mouse (4‐month males and females in a 1:1 ratio), 70% decrease in PT NKA α1 expression decreased urine output (0.51±0.14 vs 1.57±0.21 mL/24h in PTα1 +/+ , p<0.001, n=16) and absolute Na + excretion (0.14±0.05 vs 0.36±0.05 mmol/24h in PTα1 +/+ , p<0.05, n=8) by 65%, without histological or functional evidence of renal injury. Those changes were driven by increased PT Na + reabsorption, as indicated by a 65% decrease in lithium clearance (4‐month males, 1344±220 vs 3932±697 mL/24h in PTα1 +/+ , p<0.001, n=12) with unchanged GFR. This hyper‐reabsorptive phenotype of PTα1 ‐/‐ mice was coupled to increased membrane abundance of NHE3 and NBCe1A, and rescued upon crossing with floxed NHE3 mice, consistent a NKA/NHE3‐dependent mechanism. A dismantlement of caveolar NKA/Src receptor complex and intracellular redistribution of pY418Src occurred in knockdown NKA α1 PT cells, and was also observed in the PTα1 ‐/‐ hypomorphic mouse. Rescue of PT cells with wild‐type but not Src signaling‐null NKA α1 restored NHE3 and NBCe1A to basal levels, indicative of a role for NKA/Src receptor function in the tonic inhibition of Na + transporters in the PT. Hence, NKA signaling exerts a tonic inhibition on Na + reabsorption by regulating key apical and basolateral Na + transporters. This action, which is lifted upon NKA genetic suppression in cells and in vivo , tonically counteracts NKA's ATP‐driven function of basolateral Na + reabsorption. Strikingly, NKA/Src signaling is not only physiologically relevant, it is functionally dominant over NKA ion‐pumping in the control of PT reabsorption. NKA signaling therefore provides a long sought‐after mechanism for the natriuretic action of endogenous NKA ligands such as cardiotonic steroids.

11014 Background: The well-being of oncology providers (OP) is in jeopardy with increasing workload, limited resources, and personal challenges that result from the COVID-19 pandemic. We aim to evaluate the impact of COVID-19 on work-related (WR) satisfaction and fatigue among OP in Latin America. Methods: We conducted an international cross-sectional online survey of OP practicing in Latin America. The survey was administered in English, Spanish, and Portuguese. Data was analyzed using descriptive statistics and Chi-square tests. Results: In August 2020, 704 OP from 20 Latin American countries completed the survey (77% of 913 who started the survey). Table outlines baseline characteristics. Higher frequency of WR fatigue (67% vs. 58%, p=0.010) and exhaustion (81% vs. 70%, p=0.001) were reported by OP who cared for patients with COVID-19, compared to OP who cared for patients without COVID-19. Providers that observed delays in referrals to radiation (p=0.002) and surgery (p=0.04) reported WR fatigue at higher rates than their counterparts. Higher exhaustion (p=0.016) and dissatisfaction (p=0.046) were reported by OP who lacked access to supportive services, as social work. A significantly higher proportion of women reported WR fatigue (72% vs. 56%, p=0.003) and exhaustion (86% vs. 68%, p=0.001), when compared to men. Women were more likely than men to endorse higher current levels of fatigue when compared to pre-COVID-19 (61% vs. 46%, p=0.0001). To reduce stress, women were more likely than men to cut the time spent watching the news (p=0.002). Both genders declined research collaborations and speaking opportunities. Conclusions: Fatigue and dissatisfaction with work-life were prevalent among OP in Latin America. Higher rates of WR fatigue were seen in women, OP caring for patients with COVID-19, and OP with patients who experienced cancer care delays. Our data imply that OP may be a prime target for psychosocial support, particularly as current challenges will continue for the foreseen future. Baseline characteristics (N=704).[Table: see text]

1537 Background: The severe acute respiratory syndrome 2 (SARS-cov-2) virus causing COVID-19 has brought great challenges to global health services affecting cancer care delivery, outcomes, and increasing the burden in oncology providers (OP). Our study aimed to describe the challenges that OP faced while delivering cancer care in Latin America. Methods: We conducted an international cross-sectional study using an anonymous online survey in Spanish, Portuguese, and English. The questionnaire included 43 multiple choice questions. The sample was stratified by OP who have treated patients with COVID-19 versus those who have not treated patients with COVID-19. Data was analyzed with descriptive statistics and Chi-square tests. Results: A total of 704 OP from 20 Latin American countries completed the survey (77% of 913 who started the survey). Oncologists represented 46% of respondents, followed by 25% surgical-oncologists. Of the respondents, 56% treated patients with COVID-19. A significant proportion of OP reported newly adopting telemedicine during COVID-19 (14% vs 72%, p=0.001). More than half (58%) of OP reported making changes to the treatments they offered to patients with cancer. As shown in the table, caring for patients with COVID-19 significantly influenced practice patterns of OP. Access to specialty services and procedures was significantly reduced: 40% noted significantly decreased or no access to imaging, 20% significantly decreased or no access to biopsies, 65% reported delays in surgical oncology referrals, and 49% in radiation oncology referrals. A vast majority (82%) reported oncologic surgeries were delayed or cancelled, which was heightened among those treating patients with COVID-19 (87% vs 77%, p=0.001). Conclusions: The COVID-19 pandemic has significantly affected the way cancer care is delivered in globally. Although changes to healthcare delivery are necessary as a response to this global crisis, our study highlights the significant disruption and possible undertreatment of patients with cancer in Latin America that results from COVID-19.[Table: see text]

Purpose: Common celiomesenteric trunk (CMT) is a rare anatomical variation that occurs in 0.5% to 3.4% of the general population. Its presence may complicate planning and implantation of fenestrated and branched stent-grafts because the wide diameter and short length of the CMT to its bifurcation does not allow sufficient sealing for placement of bridging stents. Case Report: We report a patient with thoracoabdominal aortic aneurysm (TAAA) and CMT treated by fenestrated-branched endovascular aortic repair (FB-EVAR) using double kissing directional branches to incorporate the celiac axis and superior mesenteric artery. Pitfalls of stent design and implantation are outlined. Conclusion: Double kissing directional branches should be considered as an alternative to incorporate vessels with early bifurcation such as a CMT.