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BACKGROUND: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC). OBJECTIVE: To compare the efficacy and safety of the two most commonly used cisplatin-based regimens; gemcitabine, and cisplatin (GC) vs. accelerated (dose-dense: dd) or conventional methotrexate, vinblastine, adriamycin, and cisplatin (MVAC). METHODS: We searched MEDLINE, Embase, Scopus and other sources. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model. RESULTS: We identified 24 studies. Efficacy outcomes were comparable between MVAC and GC for MIBC. dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95%CI 1.15–1.82) and all-cause mortality at longest follow-up (OR 0.63; 95%CI 0.44–0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95%CI 0.13–0.80), anemia (OR 0.32; 95%CI 0.18–0.54), nausea and vomiting (OR 0.27; 95%CI 0.12–0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3–4 thrombocytopenia (OR 4.70; 95%CI 1.59–13.89) and a lower risk of nausea and vomiting (OR 0.05; 95%CI 0.01–0.31). Certainty in the estimates was very low for most outcomes. CONCLUSIONS: Efficacy and safety outcomes were comparable between MVAC and GC for MIBC. Including non-peer-reviewed studies showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice.

5552 Background: It has long been identified that black women with ovarian cancer have worse overall survival when compared to white women. Disparities in the adherence to NCCN guideline-directed treatment and socioeconomic characteristics may be responsible for the differences in these outcomes. Methods: A retrospective review of National Cancer Database (NCDB) was performed to identify patients diagnosed with ovarian cancer from 2012-2016. We defined adherence to NCCN (National Comprehensive Cancer Network) guidelines as having stage and year-appropriate chemotherapy and surgery. Differences in guideline adherence, socioeconomic characteristics and survival outcomes were assessed. Results: In total, 32,163 were identified meeting the study criteria; 27,744 identified their race as “white” and 2,204 identified their race as “black”. Characteristics associated with higher likelihood of black race were advanced stage of disease- stage III (OR = 1.1869, CI = 1.03-1.37) or stage IV disease (OR = 1.4495, CI = 1.23-1.70) and treatment in a comprehensive (OR = 1.5757, CI = 1.16-2.15) or academic (OR = 2.3023, CI = 1.70-3.12) treatment facility. Variables associated with a lower likelihood of black race were higher education level (OR for high school degree < 6.5 % = 0.2501, CI = 0.21-0.30) and higher median household income (OR for income > $63,333 = 0.4218, CI = 0.36-0.49). Whether the care received was adherent to NCCN guidelines did not seem to be associated with black race (OR for adherence = 1.0021, CI = 0.89-1.13). 5-year overall survival for patients who received adherent care was 58% for white patients vs. 49% for black patients. Among those who didn’t receive adherent care, the outcomes were 49% among white patients vs. 38% among black patients. Conclusions: Overall survival remains worse for black patients, regardless of whether their care adhered to NCCN guidelines as defined by our study. This suggests that while receipt of care that is not adherent to NCCN guidelines seems to be negatively associated with overall survival, we must consider and evaluate other socioeconomic, environmental and system factors that are contributing to this continued survival discrepancy in women being treated for ovarian cancer.

Over the past decade, an emerging number of blogs, podcasts, websites, and social media channels report on news from an intersectional perspective, actively considering the intersecting impact of r...

Cancer immunotherapy has revolutionized the field of oncology in recent years. Harnessing the immune system to treat cancer has led to a large growth in the number of novel immunotherapeutic strategies, including immune checkpoint inhibition, chimeric antigen receptor T-cell therapy and cancer vaccination. In this review, we will discuss the current landscape of immuno-oncology research, with a focus on elements that influence immunotherapeutic outcomes. We will also highlight recent advances in basic aspects of tumor immunology, in particular, the role of the immunosuppressive cells within the tumor microenvironment in regulating antitumor immunity. Lastly, we will discuss how the understanding of basic tumor immunology can lead to the development of new immunotherapeutic strategies.

Historically, arsenic exposure has been associated with herpes zoster (HZ) infection, however the risk is not well characterized in arsenic trioxide (ATO) treated patients with acute promyelocytic leukemia (APL). We aimed to characterize the risk of HZ in 112 ATO treated patients with APL with and without antiviral prophylaxis (AVP). HZ occurred in 13/112 (11.6%) within 6 months of completing ATO, including one case of HZ encephalitis. AVP reduced the incidence of HZ (17.5% vs. 4.1%, RR 0.24 [95% CI 0.05-1.0

The use of social media by Black women and femmes to talk about topics from a Black feminist perspective has been explored within the larger context of studies on Black Twitter and content analysis of circulated Tweets online. However, studies have yet to empirically study Black feminist social media communities' nuanced dynamics by directly speaking to those involved across a range of networked conversations. To fill this gap, this study conducted 21 semi-structured, in-depth interviews with individuals who engaged in eight different black feminist hashtag conversations across Twitter and Instagram to expand our current understanding of how black feminist intellectual production has been developed and broadened through the affordances of digital media. Findings suggest that while black feminist hashtag discussions have allowed Black women to “talk back” to hegemonic mainstream and popular discourses about Black women, these conversations are constantly at stake of appropriation and co-optation, replicating historical erasure of Black women’s intellectual production.

Thrombotic Thrombocytopenic Purpura (TTP) is a challenging thrombotic diathesis which requires prompt diagnosis and therapeutic intervention in order to avoid life-threatening consequences. There are two forms of TTP, congenital and acquired, with the acquired form constituting about 90% of cases. Both forms are associated with a deficiency of ADAMTS-13, a metalloproteinase enzyme responsible for cleaving ultra-large von Willebrand factor (uLvWF), preventing its pathologic accumulation. Within the last year, many of the diverse and serious effects of the COVID-19 virus have come to recognition, with some of the most dire consequences involving devastating vascular and hematologic complications. As with many viruses, it seems that the endothelium and the vasculature are often prime targets. Here, we report a case of a 30 year old male who was diagnosed with TTP approximately one week after a positive COVID-19 test result. He responded appropriately to plasma exchange (PLEX), caplacizumab, and steroids. We believe it is important to investigate a potential link between these two conditions, as TTP has significant morbidity and mortality risk if left unattended. We hope that our report will contribute to a better understanding of this potential link.

Jump starting pathogen evolution Mycobacteria are mostly environmental saprotrophs, but during human history, some have become our pathogens. In the past 50 years or so, intractable and virulent infections of Mycobacterium abscessus have emerged in people with cystic fibrosis. Bryant et al. investigated how these mycobacteria have evolved into human pathogens so quickly (see the Perspective by Brugha and Spencer). Chronic infections in the lung offer plenty of evolutionary scope for the emergence of virulent clones after horizontal gene transfer and hypermutation. Pathogens are acquired by environmental contamination, which leaves open a window for clinical control because the most virulent clones survive poorly outside the body. Therefore, immediate treatment and enhanced infection-control measures for M. abscessus cases could reduce opportunities for the evolution of direct person-to-person transmission. Science , this issue p. eabb8699 ; see also p. 465

BACKGROUND/AIM Cutaneous manifestations of disease are exceedingly rare and commonly overlooked in clinical practice. Allergies or contact dermatitis, autoimmune disease or skin cancer are the most common conditions typically associated with skin lesions. Rarely, cutaneous lesions may be the first sign of internal malignancy, or even resemble recurrent disease in those with history of cancer. CASE REPORT Herein, we report a case of an otherwise healthy male who presented to his primary care provider (PCP) with a skin lesion misdiagnosed as a furuncle, which eventually led to diagnosis of metastatic esophageal cancer. The patient was a 64-year-old male, presenting with a fungating lesion on the tip of his nose which was biopsied, confirming adenocarcinoma likely from a gastrointestinal source. Staging imaging showed extensive lung, liver, and boney metastatic disease. He was initially treated with chemotherapy and trastuzumab. CONCLUSION Cutaneous lesions are a rare presenting sign of malignancy, but rapidly growing lesions should be evaluated for possible metastatic disease.

Introduction Acute purulent pericarditis is an exceedingly rare entity most often caused by direct intrathoracic contamination or hematogenous spread of a bacterial infection. Mortality nears 100% when left untreated. We present here a rare case of idiopathic bacterial pericarditis caused by methicillin-sensitive Staphylococcus aureus (MSSA). Case A 69-year-old male presented with chest pain and abdominal pain. He was found to have a pericardial effusion and tamponade and underwent emergent pericardiocentesis. Pericardial fluid culture grew methicillin-sensitive Staphylococcus aureus. The patient required multiple pericardial washouts and was then treated with four weeks of intravenous antibiotics. Conclusion While uncommon, clinical suspicion for purulent pericarditis should remain high due to the associated high mortality.

Sickle cell anemia patients often present to the hospital with acute vaso-occlusive pain crisis. Symptoms can include, but are not limited to, chest pain, abdominal pain, and musculoskeletal pain. These symptoms are brought about due to the pathology of the disease. Abnormal hemoglobin S causes red blood cells to band together, otherwise known as "sickling." These patients also often present with very low hemoglobin levels on initial evaluation. In most cases, packed red blood cell transfusions are needed in order to replenish these patient's functional hemoglobin supply. Unfortunately, transfusing sickle cell patients can lead to an unwanted consequence, that of hyperhemolysis syndrome, in which blood transfusions prompt further hemolysis of the already sickled red blood cells. When this complication arises, caution must be exercised in deciding the next steps of treatment.

Dendritic cells (DCs) are professional antigen-presenting cells providing costimulatory signals to adaptive immune cells. Currently, the lack of strategies to improve antigen presentation is a hindrance in tumor immunology. Despite studies focusing on antigen cross-presenting Type-1 DCs (DC1s), a study published by our lab revealed Type-2 DCs (DC2s) with significant survival across multiple human cancers. Our research group has a long-term interest in studying immune chaperone GP96, which is an essential molecular chaperone for TLRs, GARP, and other vital innate receptors. The immune-related client network of GP96 creates opportunities to unmask the roles of multiple receptors on DCs. We have generated DC-specific GP96 deficient mice and reported increased tumor-infiltrating DC2 and delayed tumor development on the spontaneous breast cancer model. However, the mechanism by which GP96 regulates DCs function is under investigation. Using different tumor models, we found that deletion of GP96 on DCs improved immune response and decreased tumor growth. However, macrophage-GP96KO mice showed a loss of benefits observed on DC-GP96KO mice. Also, differential stimulatory/inhibitory molecules on DC1 vs. DC2 were tumor-dependent. To determine the role of DC-intrinsic GP96 in T cell activation, we used in vitro antigen-cross presentation assay. We found that OT-I CD8+ T cell activation was delayed at the initial days of the co-culture with GP96KO DCs but restored in the late phase compared with WT DCs. Collectively, the results show beneficial inflammatory DC2 molecular activation, with DC1 able to cross-present antigens to CD8+ T cells. Our study indicated that targeting GP96 on DCs may contribute to shaping T cell anti-tumor immunity. Supported by grants from NIH NCI (R01:CA193939) and NIH NIAID (U01:AI125859)

Over the past year, many young creators who use the Chinese-owned social networking platform TikTok have claimed that its underlying algorithm surveils and suppresses the reach of content by Black, brown, fat, queer, and disabled creators. However, despite these algorithmic biases, these marginalized creators have continued to find new and ingenious ways to not only create but also successfully share anti-racist, anti-misogynistic, LGBTQIA+supportive, and body-positive content on the platform. Using this tension, this essay engages visual content analysis and critical technocultural discourse analysis to examine the innovative ways marginalized creators employ TikTok’s various medium and technological affordances to evade algorithmic surveillance and oppression. Building on Simone Browne’s concept of dark sousveillance, I theorize these practices as acts of digital dark sousveillance, defined within the essay as the use of digital tools to enact surveillance subversion, obfuscation, inversion while operating within systems of racializing surveillance.

Mycobacterium tuberculosis, the causative agent of tuberculosis disease, remains a public health crisis on a global scale, and development of new interventions and identification of drug resistance are pillars in the World Health Organization End TB Strategy. Leveraging the tractability of the TM4 mycobacteriophage and the sensitivity of the nanoluciferase reporter enzyme, the present work describes an evolution of phage-mediated detection and drug susceptibility testing of M. tuberculosis, adding a valuable tool in drug discovery and basic biology research. With additional validation, this system may play a role as a quantitative phenotypic reference method and complement to genotypic methods for diagnosis and antibiotic susceptibility testing., Phenotypic testing for drug susceptibility of Mycobacterium tuberculosis is critical to basic research and managing the evolving problem of antimicrobial resistance in tuberculosis management, but it remains a specialized technique to which access is severely limited. Here, we report on the development and validation of an improved phage-mediated detection system for M. tuberculosis. We incorporated a nanoluciferase (Nluc) reporter gene cassette into the TM4 mycobacteriophage genome to create phage TM4-nluc. We assessed the performance of this reporter phage in the context of cellular limit of detection and drug susceptibility testing using multiple biosafety level 2 drug-sensitive and -resistant auxotrophs as well as virulent M. tuberculosis strains. For both limit of detection and drug susceptibility testing, we developed a standardized method consisting of a 96-hour cell preculture followed by a 72-hour experimental window for M. tuberculosis detection with or without antibiotic exposure. The cellular limit of detection of M. tuberculosis in a 96-well plate batch culture was ≤102 CFU. Consistent with other phenotypic methods for drug susceptibility testing, we found TM4-nluc to be compatible with antibiotics representing multiple classes and mechanisms of action, including inhibition of core central dogma functions, cell wall homeostasis, metabolic inhibitors, compounds currently in clinical trials (SQ109 and Q203), and susceptibility testing for bedaquiline, pretomanid, and linezolid (components of the BPaL regimen for the treatment of multi- and extensively drug-resistant tuberculosis). Using the same method, we accurately identified rifampin-resistant and multidrug-resistant M. tuberculosis strains. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis disease, remains a public health crisis on a global scale, and development of new interventions and identification of drug resistance are pillars in the World Health Organization End TB Strategy. Leveraging the tractability of the TM4 mycobacteriophage and the sensitivity of the nanoluciferase reporter enzyme, the present work describes an evolution of phage-mediated detection and drug susceptibility testing of M. tuberculosis, adding a valuable tool in drug discovery and basic biology research. With additional validation, this system may play a role as a quantitative phenotypic reference method and complement to genotypic methods for diagnosis and antibiotic susceptibility testing.

Introduction Primary CNS lymphoma (PCNSL) is an aggressive form of lymphoid malignancy that occurs exclusively in the brain, meninges, spinal cord, and eyes. The incidence of PCNSL has been increasing, particularly in the elderly population, with a median age at diagnosis of 66 years (Olson J.E. et al., Cancer 2002). The primary modality of treatment for this deadly disease is systemic chemotherapy that includes high-dose methotrexate (HD-MTX), with or without whole-brain radiation. Due to the toxicity of HD-MTX, physicians tend to avoid using it in the elderly population. This was confirmed in previous reports from the 1990s (Panageas K.S. et al., Cancer 2007). In this comprehensive population-based analysis, we sought to examine the patterns of treatment and survival in elderly patients in the 2000s and sought to investigate clinical and socioeconomic predictors of treatment selection. Methods We conducted a retrospective cohort analysis using de-identified data accessed from the national cancer database (NCDB). The NCDB provided records of 2985 patients diagnosed with PCNSL between 2004 and 2015. We excluded patients who are younger than 65 years old, those who tested positive for HIV, and those who started treatment >120 days since diagnosis to account for immortal time bias. Patients were divided into four groups based on treatment received: combined modality treatment (CMT), chemotherapy alone, radiation alone, and no treatment. Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Multivariate regression models were used to analyze predictors of the selection of any treatment versus no treatment and for selecting chemotherapy versus no chemotherapy. To account for variable baseline characteristics, we used propensity score weighting methodology to calculate estimates of interest. Survival estimates were performed using the Kaplan-Meier method, and survival differences were tested using the wilcoxon-rank test. Results We identified 1096 patients with PCNSL who fulfilled the inclusion criteria. The median age was 73 (IQR: 68-79). There were 52% males. The majority of the patients were whites (92%), lived in a metropolitan area (78%), treated at an academic/research center (57%). The most common treatment modality used was chemotherapy alone (48%), followed by CMT (22%), no treatment (16%), and radiation alone (13%). On multivariate analysis, age (OR: 0.94, 95% CI 0.92-0.96) and comorbidity score (OR: 0.63, 95% CI 0.52-0.76) significantly predicted receiving any type of treatment. Both age (OR: 0.91, 95% CI 0.89-0.94) and distance (OR: 1.006, 95% CI 1.001-1.01) were predictors of receiving chemotherapy. Median follow up was 12 months (IQR: 3-44). Median OS in months for the four groups was: 43.1 for CMT, 19.4 for chemotherapy alone, 17.2 for radiation alone, and 2.3 for no treatment. (wilcoxon-rank test p-value: 75 year old had lower median OS in general, but receiving CMT had a survival advantage as well. (Figures 1 and 2) Conclusions The majority of PCNSL patients in our analysis received treatment. Our results showed an increased trend of chemotherapy use in elderly patients compared with earlier reports, where radiation alone was the most common treatment modality. The median OS of patients was longer compared with the 1990s data (17 vs. 7 months). CMT was associated with better OS compared with no treatment and chemotherapy alone. Although this was numerically better compared with radiation alone, it was not statistically significant. Younger patients and patients with lower comorbidity scores were more likely to receive treatment. Younger patients and patients who live further from the treating facility were more likely to receive chemotherapy. Longer distance may have led to less radiation use due to the need for complex planning and frequent visits associated with radiation therapy. Our study is limited by its retrospective nature, which makes it at risk of selection bias. Using propensity score weighting methodology strengthens our results. Also, the NCDB lacks certain pertinent variables, such as details of chemotherapy regimens, and toxicity information especially for radiation in the CMT arm which will have practical implications. Disclosures Fazal: Glaxosmith Kline: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Karyopham: Speakers Bureau; Celgene: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jansen: Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau. Kahn:Genetech: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Seattle Genetics: Honoraria; Abbvie: Honoraria; Celgene: Honoraria; AstraZeneca: Honoraria; Beigene: Honoraria.

Introduction Determining eligibility for autologous hematopoietic stem cell transplantation (Auto-HCT) is considered standard of care for patients with newly diagnosed multiple myeloma (MM). In addition to comorbidity score, age >65 years is still a commonly used criterion to deem patients ineligible for transplant. Here we report the outcomes of patients ³ 65 years with MM who underwent Auto-HCT following risk stratification using HCT-CI along with other eligibility criteria. Methods We performed a retrospective analysis of 102 patients, who underwent Auto-HCT between 1/1/1999 and 12/31/2018 at Allegheny Health Network Cancer Institute. Ninety two patients (90%) received conditioning with Melphalan 200 mg/m2. Median overall survival (OS) was estimated at day+100, day+180, 1, 2, 3 and 5 years post Auto-HCT. Non-relapse mortality (NRM) was assessed at day 100 post Auto-HCT. Results For a cohort of 102 patients, a total of 119 Auto-HCT were performed. Median age at transplantation for the entire cohort was 69.2 years (65.1 - 79.4 years). Thirty five (34.3%) patients were aged ³70 years. Median HCT-CI score was 3 (range: 0-8). Median time to Auto-HCT following diagnosis was 9.1 months (range: 4.7- 176.7 months). Median time to ANC500 and PLT20 was 13 days (range: 10-15) and 18.4 days (range:8-42) respectively. Median OS by Kaplan-Meier analysis for the entire cohort vs patients ³ 70 years at day+100, day+180, 1, 2, 3, and 5 years post Auto-HCT was 97.1%, 95.1%, 91.2%, 83.3%, 78.4%, and 63.7% respectively vs 100%, 100%, 97.1%, 82.9%, 77.1% and 68.6% respectively. Median OS in months for patients Conclusion Auto-HCT in patients with MM aged ³65 years is safe, effective and should be offered to all patients with a reasonably good performance status. A fully integrated approach is required to accomplish the needs of elderly patients including consideration for quality of life.

e16147 Background: Gall bladder (GB) cancer is rare but an aggressive disease especially when presenting at an advanced stage. There is controversy regarding the best treatment approach for locally advanced disease. In this NCDB analysis, we aim to study treatment patterns for T3, T4, and/or N1 GB cancer and estimate survival for each treatment modality. We also sought to investigate clinical and socioeconomic predictors of treatment selection. Methods: We conducted a retrospective cohort analysis using de-identified data accessed from the NCDB. The NCDB provided records of 39,229 patients diagnosed with GB cancer between 2004-2017. We excluded patients who were not treated at the reporting facility, those with no histologic confirmation of the diagnosis, those with no survival data available and those with T1, T2 and metastatic disease. We did exploratory analysis and divided patients into six arms based on treatment modality (Table). Stepwise multivariable regression models were used to analyze predictors of treatment selection. Survival estimates were calculated using the Kaplan Meier and proportional Cox hazard regression methods. Results: We identified 7,004 patients with GB cancer who fulfilled the inclusion and exclusion criteria. Median age was 68 years. There were 69.5% females, and the majority of patients were white (66.1%). Receiving treatment at an academic/research center (OR 0.37, 95% CI 0.19-0.73, p

e16258 Background: Cytotoxic chemotherapy remains the standard of care in the treatment of pancreatic ductal adenocarcinoma (PDAC). There is more excitement in the last few years regarding the use of neoadjuvant chemotherapy even when the disease is resectable. In this analysis, we sought to study the different regimens used in our institutions, in regards to setting and toxicity. Methods: We retrospectively reviewed all patients diagnosed with pancreatic adenocarcinoma at Allegheny General Hospital between 2009-2020. Data was extracted from electronic medical records and de-identified. Institutional Review Board approval was obtained. Descriptive analysis was undertaken and multivariate analysis was performed to compare differences in the prevalence of toxicity across the regimens and demographics using Stata version 16. The primary outcome was the rate of toxicity that prompted dose adjustment, stratified by the setting chemotherapy was administered (neoadjuvant, adjuvant, or palliative). Results: Of the 121 patients studied, 88 patients received chemotherapy. Median age was 69 years. 66 patients (55%) were females. 40 patients suffered from adverse effects requiring a dose adjustment. 85% of the adverse effects occurred in Caucasians. 15 out of 37 patients (42.9%) who received Folfirinox, 15 out of 31 patients (48.4%) who received gemcitabine and nab-paclitaxel, 6 out of 10 patients (60.0%) who received gemcitabine and capecitabine, 3 out of 4 patients (75.0%) who received gemcitabine monotherapy required dose adjustment (table). Folfirinox and gemcitabine with nab-paclitaxel were statistically compared and found to be not significant (p-value=0.12). No significant impacts of race, gender, or age were noted in a multivariate model. Conclusions: Approximately 42% of patients receiving chemotherapy suffered from toxicities that required dose adjustments. We found a trend toward more use of neoadjuvant chemotherapy in resectable PDAC with a similar toxicity rate compared with other settings.[Table: see text]

e16214 Background: Pancreatic ductal adenocarcinoma (PDAC) cancer portends a poor prognosis with a high case-fatality rate. Venous thromboembolism (VTE) is a common complication in PDAC, due expression of tissue factor on neoplastic cells. Per most recent guidelines, anticoagulation for primary prophylaxis (PPx) of VTE is to be considered based on the Khorana score. The purpose of this study is to identify patients with PDAC and compare the outcomes of those receiving anticoagulation for primary prophylaxis versus those who did not. Methods: We performed a retrospective review of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Summary statistics were presented using percentages for categorical variables and medians with interquartile ranges for continuous variables. Univariable and multivariable logistic regression models were used to study the predictors of developing VTE, expressed as odds ratio (OR). Means and percentages were compared using t-test and Chi-square test, respectively. Results: Out of 171 patients, 121 received treatment at our institution and were included in the analysis. Median age was 69 years, 54 (45%) were male. The majority were white (88%). Only 92 patients had complete data regarding VTE PPx and events. 26 patients (28.2%) developed at least one VTE event. Out of 92 patients, 12 (13%) were on one form of VTE PPx and 1 had a contraindication to VTE PPx. One patient without VTE PPx died secondary to VTE. Of the patients on VTE PPx, only 3 (30%) experienced bleeding events. Seven patients were on VTE PPx prior to diagnosis of malignancy. 58 patients (63%) had a Khorana score of 2; 21 (23%) patients had a Khorana score of 3; 9 (10%) patients had a Khorana score of 4; and 4 (4%) patients had a Khorana score of 5. On univariable analysis, St. IV disease (OR 3.34, CI.22-8.40, P < 0.01), planned surgery (OR 0.26, CI 0.12-0.55, p < 0.01) and unresectable disease (OR 3.19, 95% CI 1.17-8.70, p 0.02) were predictors of developing VTE. On multivariate analysis, total pancreatectomy had a predictive association in the development of VTE (OR 5.01, 95% CI 1.65-23.60, p < 0.01). There was no difference in average time to progression (months) between patients who had VTE vs those who did not (12.5 vs 11.4, p 0.60). Conclusions: Our analysis indicate that we may be underutilizing Khorana score to prescribe VTE PPx in patients with PDAC. Additionally, patients undergoing total pancreatectomy demonstrated predictive association with the development of VTE. With these findings, we believe education and increased awareness of the importance of the Khorana score may decrease the morbidity and mortality associated with VTE in patients with PDAC. The use of electronic medical records to prompt physicians to calculate the Khorana score will also likely be a helpful tool.

e16522 Background: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC) in cisplatin-eligible patients. This systematic review and meta-analysis provide an updated efficacy and safety comparison between the two most commonly used cisplatin-based regimens; dose-dense (dd) or conventional MVAC versus GC. Methods: We searched different databases for studies comparing MVAC versus GC in the neoadjuvant setting. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model. Results: We identified 24 studies from inception to March 2020; among them 17 were peer reviewed and 7 were only reported as abstracts in national or international meetings, including a phase 3, randomized-controlled clinical trial. Among peer-reviewed published studies, efficacy outcomes such as OS, downstaging and pCR were comparable between conventional MVAC and GC for MIBC. If including non-peer-reviewed studies, dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95% CI 1.15–1.82), and OS at longest follow-up (OR 0.63; 95% CI 0.44–0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95% CI 0.13–0.80), anemia (OR 0.32; 95% CI 0.18–0.54), nausea and vomiting (OR 0.27; 95% CI 0.12–0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3–4 thrombocytopenia (OR 4.70; 95% CI 1.59–13.89) and a lower risk of nausea and vomiting (OR 0.05; 95% CI 0.01-0.31). Certainty in the estimates was very low for most outcomes. Conclusions: Among peer-reviewed published studies, efficacy and safety outcomes were comparable between conventional MVAC and GC for MIBC. However, If including non-peer-reviewed studies, this analysis showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice

Background SPR719 (the active metabolite of phosphate prodrug SPR720) belongs to a novel class which targets the ATPase subunits of gyrase by a mechanism distinct from fluoroquinolones. SPR719 has potent antibacterial activity against nontuberculous mycobacteria strains (NTM), including Mycobacterium avium, and is under development for treatment of NTM pulmonary disease. Oral efficacy of SPR720 was evaluated alone and in combination treatment in the C3HeBFeJ chronic mouse infection model which produces necrotic granulomas, similar to humans. Methods Mice were infected with a pulmonary aerosol of 1x108.5 CFU of M. avium ATCC 700898, (SPR719 MIC = 2 mg/mL). Treatment started on day 28 for 8 weeks with: saline, clarithromycin 250 mg/kg (CLR) QD, SPR720 at 10, 30 and 100 mg/kg QD, or SPR720 at 50 mg/kg BID. SPR720 at 30 mg/kg QD was also combined with CLR +/- ethambutol at 100 mg/kg (EMB), or CLR + rifabutin at 100 mg/kg (RFB) +/- EMB. Mice were evaluated for bacterial burden (CFU) on days 1, 27 and 60 after infection by plating serial dilutions of organ homogenates on nutrient 7H11 and charcoal agar plates. Lung pathology was evaluated by assessing prevalence and size of pulmonary lesions. Results CLR treatment for 28 days showed a significant reduction in the bacterial burden in the lung, spleen, and liver compared to the untreated control. SPR720 demonstrated a dose dependent reduction in bacterial burden, including at 100 mg/kg which showed a statistically significant reduction in the bacterial burden in the lung, spleen, and liver. CLR + EMB + SPR720 at 30 mg/kg reduction in the bacterial burden in the lung, spleen, and liver. RFB when added to the treatment regimen did not demonstrate enhanced efficacy compared the additive effect of EMB + CLR +/- SPR720. Lung pathology showed that lesions were less numerous and smaller in infected mice treated with all regimens. Conclusion Oral administration of SPR720 demonstrated a statistically significant reduction in the bacterial burden in all tissues with concomitant improvement in lung pathology, both alone and in combination with standard of care agents. These results support the continued development of SPR720 for treatment of NTM pulmonary infections. Disclosures Nicole S. Cotroneo, BS, Spero Therapeutics (Employee, Shareholder) Suzanne Stokes, PhD, Spero Therapeutics (Employee, Shareholder)

How do historically marginalized narratives spread on social media platforms? Developing research in collaboration with intersectional artists and community, or what we call “platforming intersectionality,” can reveal the promise and limitations of social media for bridging disparate, segregated communities, or “networked solidarity.” Using case studies of indie TV series about historically marginalized communities, we show that intersectionality can spread on corporate social media platforms, but the causes are largely visible outside of platforms, both online and offline. Basic conditions for spreading intersectional narratives may be met when the language used to describe them are simply communicated in ways algorithms and users can quickly understand. However, community members, including artists and publishers who produce for specific communities online and offline, serve as critical, under-appreciated nodes platforms leverage to spread intersectionality. We argue that reconceptualizing platforms as community-based media provides a better framework for understanding the power and limits of social media.

We investigated alternatives to whole blood for blood feeding of mosquitoes with a focus on improved stability and compatibility with mass rearing programs. In contrast to whole blood, an artificial blood diet of ATP-supplemented plasma was effective in maintaining mosquito populations and was compatible with storage for extended periods refrigerated, frozen, and as a lyophilized powder. The plasma ATP diet supported rearing of both Anopheles and Aedes mosquitoes. It was also effective in rearing Wolbachia-infected Aedes mosquitoes, suggesting compatibility with vector control efforts., Author summary Mosquito-transmitted diseases pose a serious burden to global health. Several mosquito control strategies release large numbers of modified mosquitoes into disease-endemic areas to reduce transmission. Large-scale mosquito rearing operations are necessary to support these approaches, and blood feeding of female mosquitoes is central to the success of these operations. Blood feeding is challenging, especially in the resource-poor environments where rearing for controlled releases can occur. Feeding on live humans or animals has notable logistical, ethical, economic, and safety challenges. In many circumstances, feeding blood in an artificial feeder is an attractive alternative; however, rapid degradation limits the suitability of stored blood as a reliable mosquito diet to one week. The logistics associated with sourcing blood on a weekly basis can be prohibitive. Here, we demonstrate that a simple diet consisting of plasma and ATP effectively supports propagation of Aedes, Anopheles, and Wolbachia-infected Aedes mosquitoes. In contrast to whole blood, the diet is effective after extended storage under refrigerated, frozen, and lyophilized conditions. We expect this formulation to prove useful for research and control operations with blood feeding difficulties.

Convergent evolution provides a rare, natural experiment with which to test the predictability of adaptation at the molecular level. Little is known about the molecular basis of convergence over macro-evolutionary timescales. Here we use a combination of positional cloning, population genomic resequencing, association mapping and developmental data to demonstrate that positionally orthologous nucleotide variants in the upstream region of the same gene, WntA, are responsible for parallel mimetic variation in two butterfly lineages that diverged >65 million years ago. Furthermore, characterization of spatial patterns of WntA expression during development suggests that alternative regulatory mechanisms underlie wing pattern variation in each system. Taken together, our results reveal a strikingly predictable molecular basis for phenotypic convergence over deep evolutionary time., Little is known about the genetic basis of convergent evolution in deeply diverged species. Here, the authors show that variation in the WntA gene is associated with parallel wing pattern variation in two butterflies that diverged more than 65 million years ago.