Citations

Advances in molecular profiling have led to improved understanding of glioma heterogeneity. Results have been used to inform diagnostic classification and targeted treatment strategies. Validation of these tests is necessary in the development of biomarkers that can aid in treatment decision, allowing for personalized medicine in neuro-oncologic diseases. Although not all populations have benefitted equally from awareness of and access to testing, opportunities arise regarding incorporating this testing into the standard of care for patients with glioma.

We sought to understand the common interaction between music, information and visual art. The evoked affect of college students (N = 47, F = 35, M = 11, NB = 1) were measured via The Implicit Positive and Negative Affect Test (IPANAT) after a presentation of Francisco Goya's Black Paintings. There were three randomly assigned groups with a narration about the artist's life and the significance of his paintings (group N), classical music (group M) and both (group NM). Participant's art knowledge was also assessed, as determined by the Vienna Art Interest and Art Knowledge Questionnaire (VAIAK). Group NM reported significantly lower affect scores, indicating more intense emotional experiences as opposed to other two groups (N = 47, F(2)= 4.099, p = .023). The knowledge and interest scores had no effect on the affect score. The implications of the findings and potential explanations are discussed through the lens of different models of art perception.

We read with great interest the manuscript by Brassetti et al. recently published in your journal and hope it will encourage discussion and debate around the optimization of the surgical management of patients with penile cancer (PECa) [...]

Background Dual antiplatelet therapy (DAPT) is frequently used in treating cerebral aneurysms with flow diverters (FDs), whereas single antiplatelet therapy (SAPT) is used mostly with coated FDs and in ruptured aneurysms. We conducted a systematic review and meta-analysis to explore the safety profile of SAPT in FDs. Methods PubMed, Web of Science, OVID Embase, OVID Medline, and Scopus were searched to 1st November 2022. Outcomes of interest included ischemic and hemorrhagic complications, conversion to DAPTs, and in-stent stenosis rates under long-term SAPT. SAPT is divided into aspirin (ASA) vs. non-ASA group (ticagrelor or prasugrel). Subgroup analysis was performed for ruptured vs. non-ruptured aneurysms and coated vs. non-coated FDs. All data were analyzed using R software version 4.2.2. Results Twelve studies with 240 total patients (43 patients in the ASA group and 197 patients in the non-ASA group) were included in our meta-analysis. The pooled ischemic occlusion rate was 9.8% (95% CI = 4.87−18.95: p-value = 0.09) for SAPTs. The ASA group had significantly higher ischemic complication rates compared to the non-ASA group (20.8% vs. 6.3%, respectively, p-value = 0.02). The pooled hemorrhagic complication rate was 3.5% (95% CI = 1.38−8.81: p-value > 0.99). The hemorrhagic rates of ASA group were 9.3%% (95% CI = 3.54−22.30) over the non-ASA group 2.1% (95% CI = 0.58−7.54) ( p-value > 0.99). The overall in-stent stenosis rate was 2.3% (95% CI = 1.06−5.14: p-value > 0.99). The ischemic complication rates were comparable between coated vs non-coated FDs (10.7% vs. 5.5% p-value = 0.39). In stent stenosis rate were 1.9% (95% CI = 0.72−4.96) in coated FDs over 4.4% (95% CI = 1.11−16.11) ( p-value = 0.32). The ruptured and non-ruptured groups also showed comparable results in terms of ischemic (17.6% vs. 7.1% respectively, p-value = 0.24) and hemorrhagic complications (9.8% vs. 1.1%, respectively, p-value = 0.08). Conclusions Flow diverter treatment under ASA monotherapy resulted in relatively high ischemic complication rates. However, SAPT with prasugrel or ticagrelor monotherapy is promising for coated FDs and ruptured aneurysm treatments. Given the overall small sample size and also the likely presence of known and unknown biases regarding choice of antiplatelet therapy between groups, larger cohort studies are needed to evaluate SAPT treatment outcomes.

Abstract Purpose/Background A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. Methods Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions. Findings/Results Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year. Implications/Conclusions The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries.

Thymic carcinoma is an aggressive malignancy that can be challenging to distinguish from thymoma using histomorphology. We assessed two emerging markers for these entities, EZH2 and POU2F3, and compared them with conventional immunostains. Whole slide sections of 37 thymic carcinomas, 23 type A thymomas, 13 type B3 thymomas, and 8 micronodular thymomas with lymphoid stroma (MNTLS) were immunostained for EZH2, POU2F3, CD117, CD5, TdT, BAP1, and MTAP. POU2F3 (≥10% hotspot staining), CD117, and CD5 showed 100% specificity for thymic carcinoma versus thymoma with 51%, 86%, and 35% sensitivity, respectively, for thymic carcinoma. All POU2F3 positive cases were also positive for CD117. All thymic carcinomas showed >10% EZH2 staining. EZH2 (≥80% staining) had a sensitivity of 81% for thymic carcinoma and a specificity of 100% for thymic carcinoma versus type A thymoma and MNTLS but had poor specificity (46%) for thymic carcinoma versus B3 thymoma. Adding EZH2 to a panel of CD117, TdT, BAP1, and MTAP increased cases with informative results from 67/81 (83%) to 77/81 (95%). Overall, absent EZH2 staining may be useful for excluding thymic carcinoma, diffuse EZH2 staining may help to exclude type A thymoma and MNTLS, and ≥10% POU2F3 staining has excellent specificity for thymic carcinoma versus thymoma.

Abstract The day I received news of my prostate cancer diagnosis time paused for a minute. My heart was heavy, and my mind racing and my soul appeared to leave my body as the physician kept talking. I’m looking at this doctor and having internal conversations with myself about dying. My attention switched from listening to reflecting to Fred Sanford holding his heart and saying “Elizabeth, I am coming to join you”, but my wife was right next to me holding my hand. The embrace of our interlocked fingers without saying a word to one another assured both of us this too shall pass. My knowing I had support encouraged me to begin educating myself about the science of survivorship. The presence of prostate cancer resources was absent in my community. I began reading information online to grasp a better understanding of this disease. The information gained encouraged me to request a second opinion from another oncologist. I was amaze by the difference in opinion about treatment options. I felt the urge to identify and specifically speak with other Black men going through this process. Everywhere I looked for support groups felt like removing my hands from pocket and watching lent flee from my fingers. What did I do? I registered my own prostate cancer support group with the state of Florida. The group grew from a few to 20 Black men across major metropolitan cities in Florida. These group meetings extended to men leading groups in their communities. I joined the Prostate Health Education Network as the Regional Ambassador to promote prostate awareness and clinical trials. My advocacy presence in the state of Florida led to Dr. Odedina and I crossing paths to champion elimination of prostate cancer health disparities for Black men. I am a Citizen Scientist in the lab of Dr. Odedina working on the inclusive cancer care and research equity for Black men consortium. I have co-authored publications, co-presented at conferences, served on research projects, and contributed to grant funding totaling over $25 million as a citizen scientist. Currently working on a Department of Defense funded grant focusing on the point of prostate cancer diagnosis. The project has completed several events to dispel myths about participation in clinical research while discussions about early detection is vital to improve survivorship. The reward from this work is knowing I am helping create spaces for Black men never to travel this journey alone. I believe men appreciate having a patient supporter but require fellowship with men who have traveled the road to gain navigational insights on how to maneuver across this terrain. Citation Format: AJ Merriweather, Dottington Fullwood, Che Ngufor, Jennifer Crook, Emelina Asto-Flores, Parisa Fathi, Roxana Dronca, Shannon Pressey, Folakemi Odedina. Early detection saves lives: I survived, and you can too— Any day above ground is a good day [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 727.

Abstract CD19 directed chimeric antigen receptor T (CART19) cell therapy has resulted in remarkable outcomes in B cell malignancies and was FDA approved in multiple indications. However, durable remissions are limited to 40% of treated patients. Inhibitory myeloid cells in tumor microenvironment have been found to suppress T cell expansion and contribute to failure of CART19 cell therapy. In this study, we aimed to unravel the interactions between monocytes, CART19 cells and tumor cells to understand how monocytes-CART19 cell interactions impact CART19 cell effector functions and clinical outcomes. Two sets of experiments were conducted, 1) use of healthy CART19 cells, CD19+ tumor cells, and healthy monocytes; 2) use of brexu-cel products from ZUMA-2 clinical trial treating mantle cell lymphoma (MCL), patient-matched monocytes and circulating MCL tumor cells (n = 11; 6 durable responders, 2 relapsed after initial response and 3 non-responders). CD28 costimulated CART19 (CART19-28ζ) cells generated in the lab from healthy donors were co-cultured with donor freshly isolated monocytes in the presence of Jeko-1 cells (a CD19+ MCL cell line). CART19 antigen specific proliferation was not inhibited by freshly isolated monocytes. When monocytes were co-cultured with CART19 and tumor cells, higher levels of eotaxin, GRO, MCP-3 and IL-7 were detected. When CART19 cells were co-cultured with the CD19+ JeKo-1 cells in the presence of ex vivo M2 polarized macrophages, CART19 antigen specific proliferation was inhibited (p=0.0045). Transwell experiments demonstrate that M2-induced CART19 inhibition is not contact dependent. Cytokine profile analysis indicated increased level of IL-1ra, IP-10 and MCP-1 and decreased level of IL-17A, sCD40L, IL-9 and MIP-1α when M2 macrophages were co-cultured with CART19 and tumor cells compared to co-cultures of tumor cells and CART19. Then we conducted ex vivo co-cultures of brexu-cel products, autologous monocytes and circulating MCL tumor cells from MCL patients (ZUMA-2) collected prior to CART19 cell infusion. Here we observed trends of elevation of IL-13 and IL-5 and reduction of GRO, MCP-3, MIP-1β and IL-8 in non-responders, compared to responders (durable responses or relapsed patients). Our results support that monocyte- and macrophage-dependent cytokine release could modulate CART19 effector and trafficking functions, and thus CART19 clinical outcomes. This warrants further investigation around strategies to improve durable responses to CART cell therapy. Citation Format: Kun Yun, Reona Leo Sakemura, Michelle J. Cox, Truc Huynh, Claudia Manriquez-Roman, Olivia Sirpilla, Carli M. Stewart, James H. Girsch, Ekene J. Ogbodo, Ismail Can, Brooke Kimball, Lionel A. Kankeu Fonkoua, Mehrdad Hefazi, Michael W. Ruff, Elizabeth L. Siegler, Mike Mattie, Sao-Mai Nguyen-Mau, Simone Filosto, Saad S. Kenderian. Impact of immunosuppressive monocytes on CART19 cell effector functions and outcomes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4082.