tbuckley/cabot-search huggingface dataset:
P16.09 Regulation of chromatin accessibility in the hypoxic tumor microenvironment of glioblastoma
Authors: M Dzwigonska, J Mieczkowski, P Pilanc, S Cyranowski, A Kominek, K Piwocka, B Kaminska, K B Leszczynska
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Chromatin structure is often dysregulated in cancers, including glioblastoma (GBM), the most aggressive type of primary brain tumor. GBM has the poorest prognosis with no efficient cure to date due to diffusive growth into the brain, resistance to treatments and the immunosuppressive tumor microenvironment (TME). The growth and invasiveness of GBM is supported by the heterogeneous TME including local microglia and bone-marrow-derived macrophages (collectively known as glioma-associated microglia and macrophages, GAMs). In addition, tumor hypoxia is a key factor in the progression of GBM, as it can globally and rapidly alter gene expression, induce cancer cell invasiveness, stemness and lead to therapy resistance. Hypoxia can influence the pro-tumorigenic function of GAMs by inducing the expression of cytokines and cell surface receptors. However, little is known on the hypoxia-imposed chromatin changes of GAMs and GBM cells, which can in turn impact the interaction between these cell populations. Here we analyze these changes using a single-cell method, which preserves in situ hypoxia within the TME of GBM. MATERIAL AND METHODS Single-cell Pi-ATAC-seq (Protein-indexed Assay of Transposase Accessible Chromatin with sequencing) method in a GL261 murine glioma model was used to simultaneously assess genome-wide chromatin accessibility and expression of intracellular protein markers in single cells, enabling accurate selection of hypoxic and non-hypoxic tumor cells and GAMs. Pi-ATAC-seq is used on paraformaldehyde-perfused tumors and therefore allows capturing unaltered hypoxia-dependent cellular states, that often become distorted during dissociation and preparation of fresh material in most common single-cell methods. RESULTS We optimized Pi-ATAC method in a GL261 GBM mouse model, with specific sorting of GAMs using CD11b+ immunosorting followed by separation of microglia and macrophages, based on intensity of CD45 staining. HIF-1α induction and binding of pimonidazole were used to mark hypoxic populations. Currently, we are investigating the chromatin accessibility profiles of cancer cells and GAMs within the hypoxic tumor microenvironment of GBM. Exploring open chromatin profiles in GAMs and glioma-microglia co-cultures will allow to unravel the mechanisms of chromatin accessibility modulation in the oxygen-dependent manner. CONCLUSION In summary, we optimized the Pi-ATAC method in a mouse GBM model to characterize the chromatin openness changes in GAMs and cancer cells in response to hypoxic stress. Further validation of these results will provide the potential to identify novel markers for GAMs/glioma interactions in hypoxic GBMs and develop novel therapeutic targets.
Limited benefit and high financial burden of drugs used to manage cancer-associated anorexia/cachexia syndrome (CACS).
Authors: Arjun Gupta, Leonce Nshuti, Udhayvir Singh Grewal, Ramy Sedhom, Helen Parsons, Anne Hudson Blaes, Beth A. Virnig, Maryam B. Lustberg, Ishwaria Mohan Subbiah, Ryan David Nipp, Sydney M. Dy, Stacie Dusetzina
Journal: Journal of Clinical Oncology (2021)

55 Background: To date, drugs used for CACS have limited efficacy and may have unwanted side effects. Despite this, clinicians commonly prescribe certain drugs for CACS, adding financial burden to patients through out-of-pocket costs near or at the end of life. We sought to describe the range of costs of the multiple drugs commonly used to manage CACS. Methods: We reviewed oncology, nutrition, and supportive care guidelines (ASCO, ESMO, ESPEN, MASCC) and compiled a list of drugs recommended for CACS. We also included drugs commonly used off-label in clinical practice as identified by study authors. Using GoodRx.com, we extracted available formulations (e.g., tablet [tab] vs capsule [cap] vs oral disintegrating tablet [ODT] vs solution [sol]), and brand name vs generic products for each drug. We identified the average retail price, and the lowest price with coupons, for each formulation using the most commonly used dosage for a 2-week period (typical fill). The average retail price is the cash price for consumers without prescription drug coverage. The lowest price represents a discounted, best case scenario of out-of-pocket costs for patients without prescription drug coverage. We collected data using the zip code 10065 in May 2021 to describe the range of costs of these drug formulations. Results: We included 7 drugs available in 20 formulations (Table). For a 2-week fill, the least expensive options included generic olanzapine 5 mg tab (once daily) and generic mirtazapine 15 mg tab (once daily), costing $4.50 per fill. Brand-name solutions were costly, ranging from $605.50 (megestrol acetate, Megace ES) to $1,156.30 (dronabinol, Syndros). Costs between formulations of the same drug/dosage varied widely: for olanzapine 5 mg, the lowest price varied from $4.50 [generic, tab] to $238.40 [Zyprexa zydis, brand-name, ODT]. Conclusions: We found that the costs of drugs used for CACS are highly variable, ranging from &lt; $5 to &gt; $1000 per fill. Overall there is limited data supporting use of drugs for managing CACS. Thus, our findings can help guide patient-clinician discussions about the risk/benefit ratio of a prescription for managing CACS, while highlighting the importance of seeking less expensive formulations when possible.[Table: see text]
Improving oral chemotherapy compliance and documentation in a safety-net oncology clinic.
Authors: Robert Harrison Hester, Lindsey Leigh Farmer, Rohit Vivek Goswamy, Natalie Chen, Sophia Seo-hyeon Lee, Quinne Sember, Raamis Khwaja, Akshar Dash, Daniel Nguyen, Christina S. Haddad, Andrew James Wiele, Hilary Y. Ma
Journal: Journal of Clinical Oncology (2021)

263 Background: Barriers to safe delivery of oral chemotherapy in a safety net hospital population include lack of health insurance, delays in medication delivery, and language barriers. Baseline chart review at the Lyndon B. Johnson Hospital oncology clinic revealed sparse documentation of oral chemotherapy education and compliance. Our team conducted the present quality improvement project to improve documentation of toxicity assessment, patient education, and compliance with the oral chemotherapy agents capecitabine, palbociclib, and sorafenib by 25% from October through December 2020. Methods: A set of standardized questions designed to assess for the above domains were generated in the form of an auto-populated electronic medical record phrase ("dot phrase," see Figure 1). Using weekly timed email notifications, physicians were reminded to incorporate these questions in their documentation during clinic visits. Chart review was performed to assess usage frequency of the dot phrase. A post-intervention survey was administered to assess providers' experience with use of the dot phrase, and assess barriers to consistent documentation. Results: 41 patients over 3 months were identified as taking the oral chemotherapy drugs capecitabine (68%), palbociclib (29%) or sorafenib (3%). 63% were non-English speakers. 49% had breast cancer, 39% GI cancers, and 12% other cancers. 12% of clinic visits correctly incorporated use of the dot phrase. Education on the dosing and schedule for oral chemo was addressed for 48% of patients, documentation of adverse effects was performed for 34% of patients, and assessment of medication adherence was documented for 22% of patients. While 73% of providers felt that documentation of oral chemotherapy compliance is important, 70% cited failure to remember to incorporate the dot phrase in real time as the primary reason for failure to use the dot phrase for oral chemotherapy documentation. Conclusions: Despite providers' view of documentation of oral chemotherapy toxicities and compliance as important, low uptake of the dot phrase was observed. The main barrier to use of the dot phrase was providers' forgetting to incorporate the dot phrase prior to and during their clinic charting. Future efforts should focus on automated reminders and regular assessments to increase compliance to this important quality domain. [Table: see text]
Use of Pfizer-BioNTech COVID-19 Vaccine in Persons Aged ≥16 Years: Recommendations of the Advisory Committee on Immunization Practices — United States, September 2021
Authors: Kathleen Dooling, Julia W. Gargano, Danielle Moulia, Megan Wallace, Hannah G. Rosenblum, Amy E. Blain, Stephen C. Hadler, Ian D. Plumb, Heidi Moline, Jack Gerstein, Jennifer P. Collins, Monica Godfrey, Doug Campos-Outcalt, Rebecca L. Morgan, Oliver Brooks, H. Keipp Talbot, Grace M. Lee, Matthew F. Daley, Sara E. Oliver
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) is a lipid nanoparticle-formulated, nucleoside mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 μg, 0.3 mL each) administered 3 weeks apart. In December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) as well as an interim recommendation for use among persons aged ≥16 years by the Advisory Committee on Immunization Practices (ACIP) (1). In May 2021, the EUA and interim ACIP recommendations for Pfizer-BioNTech COVID-19 vaccine were extended to adolescents aged 12-15 years (2). During December 14, 2020-September 1, 2021, approximately 211 million doses of Pfizer-BioNTech COVID-19 vaccine were administered in the United States.* On August 23, 2021, FDA approved a Biologics License Application for use of the Pfizer-BioNTech COVID-19 vaccine, Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (3). The ACIP COVID-19 Vaccines Work Group's conclusions regarding the evidence for the Pfizer-BioNTech COVID-19 vaccine were presented to ACIP at a public meeting on August 30, 2021. To guide its deliberations regarding the Pfizer-BioNTech COVID-19 vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,† and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.§ In addition to initial clinical trial data, ACIP considered new information gathered in the 8 months since issuance of the interim recommendation for Pfizer-BioNTech COVID-19 vaccine, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. The additional information increased certainty that benefits from prevention of asymptomatic infection, COVID-19, and associated hospitalization and death outweighs vaccine-associated risks. On August 30, 2021, ACIP issued a recommendation¶ for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19.
Treatment initiation with bone-targeting agents among patients with bone metastasis secondary to solid tumors or patients with multiple myeloma.
Authors: Oth Tran, Mark Hatfield, Meghan Moynihan, Neel Shah, Laurie A. Costa, Hossam Saad, Nicolas Despiegel
Journal: Journal of Clinical Oncology (2021)

309 Background: Recent real-world evidence is lacking regarding the initiation of bone-targeting agents (BTAs), and time to treatment with BTAs after a diagnosis of bone metastasis secondary to solid tumors (BM-ST) or multiple myeloma (MM), in both the commercially insured and Medicare Supplemental populations. Methods: Patients aged &gt;18 and newly diagnosed with BM-ST or MM during 11/1/2016-6/30/2019 (earliest diagnosis = index date) were selected from the IBM MarketScan Commercial and Medicare Databases. Patients were continuously enrolled in the 12 months before and 6 months after the index date and had no prior evidence of BTA use, skeletal-related events (SREs), osteoporosis or Paget’s disease. Initiation of and time to BTA treatment (i.e., denosumab, zoledronic acid, ibandronate or pamidronate) were reported during the variable follow-up period. SREs prior to BTA use were reported and included spinal cord compression, pathological fractures, surgery and radiation to bone. Results were stratified by tumor type (BM-ST and MM) and payer (commercial and Medicare). Results: The analysis included 8,769 commercially insured patients (70% BM-ST and 30% MM [mean age 55 and 54]) and 4,100 Medicare patients (74% BM-ST and 26% MM [mean age 76 and 75]). Across payers, the most common comorbidities were pain and hypertension. BTA initiation for BM-ST and MM patients was 46% and 24% among the commercial cohort, and 33% and 18% among the Medicare cohort. Among BM-ST commercial and Medicare cohorts, respectively, the proportion initiating BTA varied by solid tumor type: 64% and 45% of breast, 43% and 37% of prostate, and 47% and 34% of lung. Mean (SD) time to BTA initiation for BM-ST and MM patients was 3.0 (4.2) and 3.7 (5.2) months for the commercial cohort, and 3.1 (4.7) and 2.9 (3.3) months for the Medicare cohort. Among patients with BTA initiation, the proportion of BM-ST and MM patients with SREs prior to BTA treatment was 33% and 31% for the commercial cohort and 23% and 26% for the Medicare cohort. Across payers, the majority of first SREs were radiation to bone for BM-ST patients and pathological fracture for MM patients. Conclusions: For commercial patients, about one-half of BM-ST patients and a quarter of MM patients initiated BTA treatment; for Medicare patients, these proportions decreased to a third and a fifth, respectively. On average, BTA initiation occurred within about 3 to 4 months from first diagnosis. The proportion of commercial and Medicare patients with SREs prior to BTA initiation was a third and a quarter, respectively. Results generated from this study should be supplemented by the evaluation of the relationship between bone protection treatment patterns and outcomes associated with BM-ST and MM.
Black multiple myeloma patients undergoing upfront autologous stem cell transplant have similar survival outcomes compared to Whites: A propensity‐score matched analysis
Authors: Romil Patel, Junsheng Ma, Qaiser Bashir, Ruby Delgado, Gabriela Rondon, Uday R. Popat, Chitra M. Hosing, Yago Nieto, Partow Kebriaei, Amin M. Alousi, May Daher, Rohtesh Mehta, Samer Srour, Donna M. Weber, Sheeba K. Thomas, Hans C. Lee, Krina K. Patel, Robert Z. Orlowski, Elizabeth S. Shpall, Richard E. Champlin, Neeraj Saini, Muzaffar H. Qazilbash
Journal: American Journal of Hematology (2021)
Changes in Emergency Department Encounters for Vomiting After Cannabis Legalization in Colorado
Authors: George Sam Wang, Christine Buttorff, Asa Wilks, Daniel Schwam, Gregory Tung, Rosalie Liccardo Pacula
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Cannabis hyperemesis syndrome is an emerging clinical issue associated with cannabis use. Legalization of cannabis has led to an increase in vomiting-related illnesses in health care settings. <h3>Objective</h3> To examine whether legalization of cannabis in Colorado has been associated with increases in vomiting-related emergency department (ED) visits. <h3>Design, Setting, and Participants</h3> A cross-sectional design was used to assess the increase in ED claims for vomiting reported to the Colorado Hospital Association between January 1, 2013, and December 31, 2018, in counties that had no prior cannabis dispensaries before legalization compared with those that did. A total of 820 778 patients seeking care through Colorado EDs were included in the analysis. <h3>Exposures</h3> The number of medical and recreational cannabis dispensaries per county per quarter. <h3>Main Outcomes and Measures</h3> County per capita rate of vomiting-related ED claims per quarter. <h3>Results</h3> Vomiting-related ED health care encounters increased from 119 312 in 2013 to 153 699 in 2018 (29% increase). Over this period, 203 861 patients (25%) were aged 0 to 18 years; 114 201 (14%) were aged 19 to 25 years, and 502 771 (61%) were aged 26 years or older; 510 584 patients (62%) were female. Additional recreational dispensaries were associated with increased vomiting-related ED visits (incidence rate ratio, 1.03; 95% CI, 1.01-1.05), but counties with high baseline medical dispensary exposure experienced smaller increases in vomiting-related ED visits than counties with no baseline medical dispensary exposure (incidence rate ratio, 0.97; 95% CI, 0.95-0.99). Counties with a high number of medical marijuana dispensaries had increases at a 5.8% slower rate than counties with none. <h3>Conclusions and Relevance</h3> The findings of this study suggest that cannabis legalization in Colorado is associated with an increase in annual vomiting-related health care encounters with regard to exposure to these markets. It may be useful for health care clinicians to be aware of cannabis hyperemesis syndrome and inquire about cannabis use when appropriate.
T-bet and RORα control lymph node formation by regulating embryonic innate lymphoid cell differentiation
Authors: Christina Stehle, Timo Rückert, Rémi Fiancette, Dominika W. Gajdasik, Claire Willis, Carolin Ulbricht, Pawel Durek, Mir-Farzin Mashreghi, Daniela Finke, Anja Erika Hauser, David R. Withers, Hyun-Dong Chang, Jakob Zimmermann, Chiara Romagnani
Journal: Nature Immunology (2021)
Pulmonary Circulation Discovery Before Ibn Nafis—Ancient Persian and Greek Theories
Authors: Arman Zargaran
Journal: JAMA Cardiology (2021)

The recognition of the pulmonary circulation is a complex evolution in medical history and draws on theories across eras and cultures.This narrative review summarizes evidence suggesting that the recognition of pulmonary circulation is older than the time of Ibn Nafis. The theory of pulmonary circulation originated in ancient Persia (ad 224-637), was overshadowed by Greek theory from the 11th century, and reestablished by Ibn Nafis in the 13th century.The findings of this review may help contextualize the story of the discovery of pulmonary circulation in ancient Persian and Greek theories before Ibn Nafis.
Infographic. Pain or injury? Why differentiation matters in exercise and sports medicine
Authors: Morten Hoegh, Tasha Stanton, Steven George, Kristian Damgaard Lyng, Sabina Vistrup, Michael Skovdal Rathleff
Journal: British Journal of Sports Medicine (2021)

Successful management of tissue injury cannot rely solely on pain responses because tissue healing is not directly related to pain. Pain without identifiable pathology is common in athletes,1 and as a result medical labelling remains an ongoing challenge. Therefore, we argue that, for the benefit of athletes, there is an urgent need for a clear distinction between pain and injury (see Infographic).

Synonymous use of pain and injury in research and clinical practice may negatively impact clinical management. First, benign and normal fluctuations in pain may be seen as signs of sports-related injury, which could impact performance negatively. Second, viewing all pain …
P04.08 Biopsy-only glioblastoma (BO-GBM) as a heterogeneous group of patients
Authors: V Harlay, A Loundou, C Boucard, G Petrirena, M Barrie, C Campello, D Autran, L Padovani, D Figarella, S Boissonneau, H Dufour, K Baumstarck, E Tabouret, O Chinot
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND “Biopsy-only” glioblastoma is associated with a heterogeneous functional and survival outcome. BO-GBM patients is an understudied group of patients associated to a poor outcome, which has been reported to represent 21% of histologically confirmed GBM in the US National Cancer Data Base. Pattern of care included radiotherapy-temozolomide (RT-TMZ) standard regimen completed in 15% of patients, any other form of oncologic treatment in 60%, and supportive care alone in 25% of patients. Our objective was to explore pattern of care and prognosis associated to BO-GBM in our center. MATERIAL AND METHODS Patients with BO-GBM included in a prospective regional glioma SIRIC cohort initiated in 2014 and closed in 2017 were retrospectively reviewed for patients characteristics, MRI finding, treatment allocation and delivery. PFS and OS were analyzed. RESULTS Of 535 patients included in the cohort, 86 patients were referred &amp;gt; 3 months post-surgery and were excluded from this analysis while 449 patients were included at initial surgery, of which 158 patients (35%) underwent biopsy only. Of 158 patients, 18 patients were excluded for missing data leaving 139 patients for the present analysis. Fifty-four (39%) were referred to RT-TMZ (50 patients completed concomitant treatment), 68 (49%) considered unfitted for RT received chemotherapy upfront (CT-UF) (of which 4 were subsequently referred to RT), 17 (12%) were referred to palliative care only (PC). Groups differed at baseline for age (mean 60, 68, and 69 years, for RT-TMZ, CT-UF, and PC respectively); for KPS (70, 60, and 50 for RT-TMZ, CT-UF, and PC respectively); for mean tumor surface measured on gadolinium-enhanced T1-weighted (793, 1420, 1412 mm2 for RT-TMZ, CT-UF, PC); for tumor extension (bilateral in 6.4% and 29.3% for RT-TMZ and CT-UF respectively); for mean steroid intake (45, 60, 100 mg daily respectively). Median OS was 14 months (95% CI, 9.65–18.71), 8 months (95% CI, 4.62–7.67), and 2 months (95% CI, 0.67–3.33) for RT-TMZ, CT-UF, and PC respectively. CONCLUSION Inoperable GBM constitute a large and heterogeneous population in which one third of patients are amenable to standard of care, with survival outcome close to the one of patients who underwent surgery. Patients considered unfit for RT-TMZ at diagnosis fail to be referred subsequently to RT after CT and exhibit a poor survival outcome. Thus, reliable criteria are needed to help selecting patients for adequate treatment while new strategies are warranted for BO-GBM unfit for RT.