tbuckley/cabot-search huggingface dataset:
Factors associated with failure to receive oral anticancer drugs.
Authors: Sahil D Doshi, Morgan RL Lichtenstein, Melissa Parsons Beauchemin, Rohit R. Raghunathan, Cynthia Law, Melissa Kate Accordino, Jason Dennis Wright, Elena B. Elkin, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2021)

41 Background: Oral anti-cancer drugs (OACDs) have become increasingly prescribed over the last 10 years and require a significant amount of care coordination. Preliminary administrative database studies have shown that 10-15% of prescriptions are never received by the patient, but the reasons behind this are poorly understood. In this study, we prospectively identified failure to receive (FR) cases in which OACD prescriptions were never received by patients, examined underlying reasons for FR, and assessed clinical and process-related factors associated with FR. Methods: We prospectively collected data on new OACD prescriptions for adult oncology patients at a large, urban academic cancer center from 1/1/2018 to 12/31/2019. We collected patient demographic, clinical, and insurance data, OACD delivery date, and interactions with payers and financial assistance groups. FR was defined as failure to receive a prescribed OACD. Reasons for FR were confirmed by manual chart review and classified into seven categories: clinical deterioration, financial access, provider-driven clinical decision making, patient-directed change, transfer of care, lost to follow up, and other. We calculated the relative proportion of each FR category and used multivariable logistic regression to identify factors associated with FR, including initiation of a prior authorization and drug class. Results: The cohort included 1,080 patients who were prescribed 1,269 new OACDs. Of these prescriptions, 13% (N=163) were categorized as FR. Among the 158 patients with FR, average patient age was 66 years, 55% identified as non-Hispanic white, 61% had any Medicare plan, 11% had Medicaid only, and 25% had commercial insurance. Overall, 18% of FR cases were attributed to clinical deterioration, 13% to financial access, 29% to provider-driven clinical decision making, 17% to patient-directed change, 13% to transfer of care, and 5% were lost to follow up. Univariate analysis showed that FR was less likely in cases where prior authorization was initiated (p &lt; 0.001) and multivariate analysis confirmed this result (OR 0.47 [CI 0.33-0.66], p &lt; 0.001). Conclusions: Though the majority of oncology patients prescribed OACDs received the drug, 13% of patients in our study experienced FR. FR is associated with a lack of prior authorization initiation, which may reflect barriers to access, a change in clinical decision-making, or patient choice. Ultimately, FR is multifactorial and may be appropriate in some cases. More work is needed to determine whether improved access would increase uptake in some patients. [Table: see text]
High-dose VitC plus oncolytic adenoviruses enhance immunogenic tumor cell death and reprogram tumor immune microenvironment
Authors: Jinhu Ma, Chunxue Zhang, Gang Shi, Dan Yue, Yongheng Shu, Shichuan Hu, Zhongbing Qi, Yanwei Chen, Bin Zhang, Yong Zhang, Anliang Huang, Chao Su, Yan Zhang, Hongxin Deng, Ping Cheng
Journal: Molecular Therapy (2021)

Preclinical and clinical studies have validated the antitumor effects of several oncolytic viruses (OVs). However, the efficacy of OVs is limited when they are administered as monotherapies. Combination therapy is a promising direction for oncolytic virotherapy in the future. A high dose of vitamin C (VitC) exerts anticancer effects by triggering the accretion of substantial amounts of reactive oxygen species (ROS). OVs can induce immunogenic tumor cell death and elicit an antitumor immune response. ROS play an important role in immunogenic cell death (ICD). This study aimed to explore whether high-dose VitC in combination with oncolytic adenoviruses (oAds) exhibited a synergistic antitumor effect. High-dose VitC synergized with oAds against tumor by enhancing immunogenic tumor cell death. Combination therapy with high-dose VitC and oAds significantly increased the number of T cells in the tumor microenvironment (TME) and promoted the activation of T cells. Furthermore, the antitumor effect of the combination therapy was CD8+ T cell dependent. In addition, combination therapy with high-dose VitC and oAds reprogramed the immunosuppressive TME. Our study provides a new strategy for combination therapy of OVs.
Cardiac Resynchronization Therapy Reduces Premature Ventricular Contractions But Not Ventricular Tachyarrhythmias in Patients with Chronic Heart Failure
Authors: Wakayama Yuji, Kumagai Koji, Fukuda Koji, Sugai Yoshinao, Hirose Masanori, Yamaguchi Nobuhiro, Shimokawa Hiroaki
Journal: Circulation (2008)
Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography in Prosthetic Pulmonary Valve Infective Endocarditis
Authors: Maëlys Venet, Zakaria Jalal, Reaksmei Ly, Sophie Malekzadeh-Milani, Sebastien Hascoët, Emmanuelle Fournier, Caroline Ovaert, Anne Claire Casalta, Clément Karsenty, Alban Elouen Baruteau, Laurianne Le Gloan, Maëlle Selegny, Stéphanie Douchin, Hélène Bouvaist, Yaniss Belaroussi, Fabrice Camou, Ghoufrane Tlili, Jean-Benoît Thambo
Journal: JACC. Cardiovascular imaging (2021)

The aim of this study was to assess the diagnostic performances of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion.PPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of 18F-FDG PET/CT remains poorly studied in PPVE.A retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent 18F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of 18F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study.A total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of 18F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). 18F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE.Using 18F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes.
P300/CBP‐associated factor (PCAF)‐mediated acetylation of Fascin at lysine 471 inhibits its actin‐bundling activity and tumor metastasis in esophageal cancer
Authors: Yin‐Wei Cheng, Fa‐Min Zeng, Da‐Jia Li, Shao‐Hong Wang, Jian‐Zhong He, Zhen‐Chang Guo, Ping‐Juan Nie, Zhi‐Yong Wu, Wen‐Qi Shi, Bing Wen, Xiu‐E Xu, Lian‐Di Liao, Zhi‐Mao Li, Jian‐Yi Wu, Jun Zhan, Hong‐Quan Zhang, Zhi‐Jie Chang, Kai Zhang, Li‐Yan Xu, En‐Min Li
Journal: Cancer Communications (2021)

Fascin is crucial for cancer cell filopodium formation and tumor metastasis, and is functionally regulated by post-translational modifications. However, whether and how Fascin is regulated by acetylation remains unclear. This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis.Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor (PCAF), and immunofluorescence was used to investigate their colocalization. An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry. A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma (ESCC) cells using Western blotting by overexpressing and knocking down PCAF expression. An in vitro cell migration assay was performed, and a xenograft model was established to study in vivo tumor metastasis. Live-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation. The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry.Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471 (K471) by PCAF. Using the specific anti-AcK471-Fascin antibody, Fascin was found to be acetylated in ESCC cells, and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown. Functionally, Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis, whereas Fascin-K471 deacetylation exhibited a potent oncogenic function. Moreover, Fascin-K471 acetylation reduced filopodial length and density, and lifespan of ESCC cells, while its deacetylation produced the opposite effect. In the filipodium shaft, K471-acetylated Fascin displayed rapid dynamic exchange, suggesting that it remained in its monomeric form owing to its weakened actin-bundling activity. Clinically, high levels of AcK471-Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease-free survival of ESCC patients.Fascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells. Fascin-K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin-bundling activity.
Association between insurance plan, prior authorization, and time to receipt of oral anticancer drugs.
Authors: Morgan RL Lichtenstein, Melissa Parsons Beauchemin, Rohit R. Raghunathan, Sahil D Doshi, Cynthia Law, Melissa Kate Accordino, Elena B. Elkin, Jason Dennis Wright, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2021)

6 Background: The past decade has seen a dramatic increase in the number of Food and Drug Administration approvals of oral anti-cancer drugs (OACDs). Most OACD prescriptions require coordination between payers and providers, which can delay drug receipt. In May 2021, two bills were introduced in the US House of Representatives (HR 3173 and HR 3258) to streamline the prior authorization (PA) process. In this study, we examined clinical and process-related factors associated with PA and time to drug receipt (TTR) for patients who received a new OACD prescription. Methods: We prospectively collected data on all new OACD prescriptions for adult oncology patients from 1/1/2018 to 12/31/2019. We collected patient demographic, medical, and insurance data, drug type (hormonal, chemotherapy, targeted), and specialty pharmacy interactions with payers and financial assistance groups, including PA information. TTR was defined as the number of days from OACD prescription to patient receipt of the drug. We used multivariable logistic regression to separately assess factors associated with TTR and factors associated with PA for patients who received a new OACD prescription. Results: The cohort for both models included 883 patients who were prescribed 1014 new OACDs. Of these prescriptions, 72.3% (N=733) required PA. The median age was 66 and 44% identified as White. The median TTR was 7 days (IQR 0 – 142; 25% ≥ 14 days; and 5% ≥ 30 days). In unadjusted analyses, PA was associated with insurance and drug type and delayed TTR was associated with PA and insurance type. In a multivariable analysis, patients with Medicaid insurance were more likely to require PA compared to patients with Medicare (OR 1.93 (1.14 – 3.32), p=0.03). In addition, patients prescribed targeted and hormone therapies were more likely to require PA than those prescribed oral chemotherapy (targeted: OR 3.33 [2.38 – 4.68], p&lt;0.001; hormone: OR 4.26 [2.45 – 7.65], p&lt;0.001). A separate multivariable analysis showed that PA is associated with delayed TTR (OR 1.62 [1.18 – 2.24], p=0.003) and that Medicaid is associated with a shorter TTR (OR 0.59 [0.37 – 0.94], p=0.03). Conclusions: The current process for obtaining OACDs is complex and multifaceted. Seventy two percent of delivered OACDs require PA, which is associated with delayed TTR. Earlier intervention and new health policies are needed to reduce time to OACD receipt. [Table: see text]
Assessment of patient satisfaction, financial, and environmental impacts of teleoncology.
Authors: Cindy Jiang, Garth William Strohbehn, Rachel Dedinsky, Shelby Raupp, Brittany Pannecouk, Sarah Elizabeth Yentz, Nithya Ramnath
Journal: Journal of Clinical Oncology (2021)

278 Background: There was rapid adoption of teleoncology at Veterans Health Administration (VHA) during the COVID-19 pandemic. One-third of 9 million VHA-enrolled Veterans live in rural areas. While digital solutions can expand capacity, enhance care access, and reduce financial burden, they may also exacerbate rural-urban health disparities. Careful evaluation of patients’ perceptions and policy tradeoffs are necessary to optimize teleoncology post-pandemic. Methods: Patients with ≥1 teleoncology visit with medical, surgical, or radiation oncology between March 2020 and June 2020 identified retrospectively. Validated, Likert-type survey assessing patient satisfaction developed. Follow-up survey conducted on patients with ≥1 teleoncology visit from August 2020 to January 2021. Travel distance, time, cost, and carbon dioxide (CO 2 ) emissions calculated based on zip codes. Results: 100 surveys completed (response rate, 62%). Table with demographics. Patients overall satisfied with teleoncology (83% ‘Agree’ or ‘Strongly Agree’) but felt less satisfied than in-person visits (47% ‘Agree’ or ‘Strongly Agree’). Audiovisual component improved patient perception of involvement in care (two-sided, p = 0.0254), ability to self-manage health/medical needs (p = 0.0167), and comparability to in person visits (p = 0.0223). Follow-up survey demonstrated similar satisfaction. Total travel-related savings: 86,470 miles, 84,374 minutes, $49,720, and 35.5 metric tons of CO 2 . Conclusions: Veterans are broadly satisfied with teleoncology. Audiovisual capabilities are critical to satisfaction. This is challenging for rural populations with lack of technology access. Patients experienced financial and time savings, and society benefitted from reduced carbon emissions. Continued optimization needed to enhance patient experience and address secondary effects.[Table: see text]
P13.21 PET-based dose painting radiation therapy strategy in a glioblastoma rat model using the small animal radiation research platform
Authors: S Donche, J Verhoeven, C Bouckaert, B Descamps, R Raedt, C Vanhove, I Goethals
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Previously, a rat glioblastoma model to mimic chemo-radiation treatment of human glioblastoma in the clinic was established. Similarly to the clinic, CT and MRI were combined during the treatment planning process. PET imaging was subsequently added which allowed us to implement sub-volume boosting using a micro-irradiation system. However, combining three imaging modalities (CT, MRI and PET) using a micro-irradiation system, proved to be labour intensive because multimodal imaging, treatment planning and dose delivery have to be completed sequentially in the preclinical setting. MATERIAL AND METHODS Two different methodologies were compared in silico for performing preclinical [18F]FET PET based radiation therapy (20 Gy based on MRI, 8 Gy boost based on PET) based on three different cases. Method 1 is based on the previously published methods1,2. However, the process is automated using an in-house developed MATLAB code. Method 2 consists of a more sophisticated method where a series of isocenters and jaw dimensions for the motorised variable collimator were determined based on the [18F]FET PET uptake. Both methods were evaluated by means of the dose volume histograms (DVH) and Q-volume histograms. RESULTS The setup parameters for both methods were calculated. The DVHs for method 2 are systematically closer to the ideal dose distribution compared to method 1. These findings are confirmed by the D90 and D50 values which are considerably lower for method 1. When observing the Q-factor, method 2 always results in dose distributions that are closer to the dose objectives (method 1: 0.141±0.046; method 2: 0.064±0.011). CONCLUSION The described novel method to optimize the preclinical treatment planning process has many advantages in terms of dose delivery, time efficiency and variability, when compared to the previously used methods1,2. These improvements are important to narrow the gap between clinical and preclinical radiation research and for the development of new therapeutics and/or radiation therapy procedures for glioblastoma. 1. Bolcaen, J., Descamps, B., Boterberg, T., Vanhove, C. &amp; Goethals, I. PET and MRI Guided Irradiation of a Glioblastoma Rat Model Using a Micro-irradiator. J. Vis. Exp. 1–10 (2017) doi:10.3791/56601. 2. Verhoeven, J. et al. Technical feasibility of [18F]FET and [18F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model. Radiat. Oncol. 14, (2019).
P14.01 Incidence and impact of venous thromboembolism and major bleeding in patients with glioblastoma
Authors: F H J Kaptein, M A M Stals, E Klaase, M Y Kapteijn, S C Cannegieter, M J B Taphoorn, L Dirven, M V Huisman, J A F Koekkoek, F A Klok
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Patients with glioblastoma are considered to be at high risk of venous thromboembolism (VTE) and major bleeding (MB), although reliable incidence estimates are lacking. The aim of this study was to assess the cumulative incidence, risk factors and prognostic impact of VTE and MB in a large cohort of glioblastoma patients. MATERIAL AND METHODS Patients diagnosed with glioblastoma between 2004–2020 from the Leiden University Medical Center and Haaglanden Medical Center were included and followed from 6 months before date of histopathological glioblastoma diagnosis up to two years after, or until an outcome of interest (VTE and MB) or death occurred. Cumulative incidences were estimated using Kaplan-Meier and cumulative incidence competing risk methods. Outcome predictors were determined with multivariable (time-dependent) Cox models. RESULTS Of the 967 included patients, 631 died, 101 were diagnosed with VTE and 130 with MB during a median follow-up of 15 months (IQR 9–22). The majority of MBs were intracranially (94%), of which half was within 4 weeks post-surgery (51%). Ambulant patients did not routinely receive pharmacological thromboprophylaxis. The adjusted 2.5-year-cumulative incidence of VTE was 12% (95%CI 10–14) and of MB 16% (95%CI 13–18). One year increase in age (HR 1.03, 95%CI 1.01–1.05), tumor resection (vs. biopsy: HR 0.56, 95%CI 0.35–0.89) and performance status (ECOG &amp;gt;1 vs ≤1: HR 1.8, 95%CI 1.2–2.7) were independent predictors of VTE (a biopsy rather than resection was performed in patients with the worst prognosis). MB and VTE predicted all-cause mortality (adjusted HR 1.7, 95%CI 1.3–2.1 and 1.3, 95%CI 0.99–1.6 respectively). CONCLUSION The incidences of VTE and MB in patients with glioblastoma are high, with both complications associated with a poor prognosis. Our observations emphasize the need for prospective studies to determine optimal thromboprophylaxis and VTE treatment strategy in these patients.
Multi-mechanical waves against Alzheimer’s disease pathology: a systematic review
Authors: Francisca Monteiro, Ioannis Sotiropoulos, Óscar Carvalho, Nuno Sousa, Filipe S. Silva
Journal: Translational Neurodegeneration (2021)

Abstract Alzheimer’s disease (AD) is the most common cause of dementia, affecting approximately 40 million people worldwide. The ineffectiveness of the available pharmacological treatments against AD has fostered researchers to focus on alternative strategies to overcome this challenge. Mechanical vibrations delivered in different stimulation modes have been associated with marked improvements in cognitive and physical performance in both demented and non-demented elderly. Some of the mechanical-based stimulation modalities in efforts are earlier whole-body vibration, transcranial ultrasound stimulation with microbubble injection, and more recently, auditory stimulation. However, there is a huge variety of treatment specifications, and in many cases, conflicting results are reported. In this review, a search on Scopus, PubMed, and Web of Science databases was performed, resulting in 37 papers . These studies suggest that mechanical vibrations delivered through different stimulation modes are effective in attenuating many parameters of AD pathology including functional connectivity and neuronal circuit integrity deficits in the brains of AD patients, as well as in subjects with cognitive decline and non-demented older adults. Despite the evolving preclinical and clinical evidence on these therapeutic modalities, their translation into clinical practice is not consolidated yet. Thus, this comprehensive and critical systematic review aims to address the most important gaps in the reviewed protocols and propose optimal regimens for future clinical application.
Percutaneous Myocardial Revascularization in Late-Presenting Patients With STEMI
Authors: Frédéric Bouisset, Edouard Gerbaud, Vincent Bataille, Pierre Coste, Etienne Puymirat, Loic Belle, Clément Delmas, Guillaume Cayla, Pascal Motreff, Gilles Lemesle, Nadia Aissaoui, Didier Blanchard, François Schiele, Tabassome Simon, Nicolas Danchin, Jean Ferrières
Journal: Journal of the American College of Cardiology (2021)
Case 28-2021: A 37-Year-Old Woman with Covid-19 and Suicidal Ideation
Authors: Carol S. North, Emily M. Sorg, SooJeong Youn, Jacqueline T. Chu
Journal: New England Journal of Medicine (2021)

A Woman with Covid-19 and Suicidal Ideation A 37-year-old woman was admitted to the hospital because of suicidal ideation during the Covid-19 pandemic. She had presented with symptoms consistent wi...