tbuckley/cabot-search huggingface dataset:
Incidence and Prevalence of Granuloma Annulare in the United States
Authors: John S. Barbieri, Olaf Rodriguez, Misha Rosenbach, David Margolis
Journal: JAMA Dermatology (2021)

Although several single-center studies have estimated that granuloma annulare may account for approximately 0.1% to 0.4% of new patients presenting to dermatologists, large-scale population-based studies estimating the prevalence and incidence of granuloma annulare are lacking.To estimate the population-based incidence and prevalence of granuloma annulare in the United States and to identify the most commonly prescribed treatments.This cross-sectional study used deidentified data from the Optum Clinformatics Data Mart Database from January 1, 2017, to December 31, 2018, to identify patients with granuloma annulare.After validating an approach to classify patients with granuloma annulare using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes, the primary outcomes were age-, sex-, and race/ethnicity-specific annualized incidence and prevalence estimates for granuloma annulare. In addition, treatment use within 6 to 12 months after the first diagnosis of granuloma annulare was examined. Confidence intervals for prevalence and incidence estimates were computed assuming a binomial distribution using the Wilson score method. Age-, sex-, and race/ethnicity-specific incidence and prevalence estimates were compared using the χ2 test.A total of 11 608 patients with incident granuloma annulare (8680 female patients [74.8%]; mean [SD] age, 56.5 [18.8] years) and 17 862 patients with prevalent granuloma annulare (13 548 female patients [75.8%]; mean [SD] age, 56.6 [18.5] years) were identified during the study period. The overall annualized incidence of granuloma annulare was 0.04%, or 37.9 (95% CI, 36.9-38.9) per 100 000, and the overall annualized prevalence of granuloma annulare was 0.06%, or 58.3 (95% CI, 57.1-59.5) per 100 000. The incidence and prevalence of granuloma annulare were highest in the fifth decade of life. The incidence and prevalence of granuloma annulare were higher among women (incidence: female to male ratio, 2.8:1; prevalence: female to male ratio, 3.0:1). Within 6 months of their first diagnosis, 4822 patients (41.5%) filled a prescription for a topical corticosteroid, and 1087 patients (9.4%) received an intralesional injection. Within 6 months of their first diagnosis, oral tetracycline prescriptions were filled by 820 patients (7.1%), and hydroxychloroquine prescriptions were filled by 268 patients (2.3%).Granuloma annulare is a rare disease in the United States that is more common among women and middle-aged to older individuals. The findings of this cross-sectional study provide important background regarding the basic epidemiology and overall burden of granuloma annulare in the United States. Future studies are needed to better understand the association of granuloma annulare with quality of life and the most optimal treatment approaches for this condition.
Composite scoring combining OncotypeDX risk with circulating tumor cell status improves prognostication.
Authors: Nadeem Bilani, Leah Elson, Elizabeth Blessing Elimimian, Hong Liang, Zeina A. Nahleh
Journal: Journal of Clinical Oncology (2021)

e12577 Background: Genomic assays, such as the 21-gene OncotypeDX (ODX) and the 70-gene MammaPrint (MP) panels, can be used to personalize treatment for women with early-stage, hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer (BC). We previously showed that 1) circulating tumor cell (CTC) status has prognostic and predictive value in BC, and that 2) there is no clear association between ODX risk and CTCs. We, hereby, assess the prognostic value of composite scoring combining ODX and CTC data. Methods: This analysis of the 2004-2017 National Cancer Database registry includes patients with early-stage (AJCC I-II), HR+/HER- BC, as well as ODX, MP, and CTC data. A composite model was created with ODX and CTC data: low-risk escalated to intermediate-risk, or intermediate- to high-risk, if positive for CTCs. The association between a) ODX, b) ODX-CTC composite, or c) MP and overall survival (OS) was examined using Cox regressions, controlling for age (50-70); and stratifying by race (White vs. Black) and tumor histology (ductal vs. lobular). Prognostic value was evaluated using Harrell’s C-index (i.e. area under ROC curve) for each model. Results: N = 841,716 patients with early-stage, HR+/HER2- BC were identified. N = 271,416 (32.2%) had ODX data, n = 12,417 (1.5%) had MP data, and n = 1,141 (0.14%) had both ODX and CTC data. Due to CTC-positivity, n = 46 patients were upstaged from low- to intermediate-risk (23.1% of all low-risk), while n = 63 patients were upstaged from intermediate- to high-risk (20.5% of all intermediate-risk) in the composite ODX-CTC model. All 3 prognostic scoring systems were associated (p &lt; 0.05) with OS as per Cox regressions. As indicated by a C-index closer to 1, MP appears superior to ODX alone at differentiating high- from low-risk based on OS (0.597 versus 0.565) patients. However, composite ODX-CTC scoring was superior to MP alone (0.673 versus 0.597). This model could not be validated in Black patients (versus White) or those with lobular histology (compared to ductal) due to limited ODX-CTC data in these groups. Conclusions: Composite ODX-CTC risk scoring appears superior to MP alone. If confirmed, this prognostic model would more accurately identify early-stage, HR+/HER2- patients requiring escalated systemic therapy including chemotherapy compared to low-risk BC. More data is needed in ethnic minorities and patients with atypical histology to validate these promising results.[Table: see text]
Cardiovascular Outcomes and Mortality Associated With Discontinuing Statins in Older Patients Receiving Polypharmacy
Authors: Federico Rea, Annalisa Biffi, Raffaella Ronco, Matteo Franchi, Simona Cammarota, Anna Citarella, Valeria Conti, Amelia Filippelli, Carmine Sellitto, Giovanni Corrao
Journal: JAMA Network Open (2021)

Polypharmacy is a major health concern among older adults. While deprescribing may reduce inappropriate medicine use, its effect on clinical end points remains uncertain.To assess the clinical implications of discontinuing the use of statins while maintaining other drugs in a cohort of older patients receiving polypharmacy.This retrospective, population-based cohort study included the 29 047 residents in the Italian Lombardy region aged 65 years or older who were receiving uninterrupted treatment with statins, blood pressure-lowering, antidiabetic, and antiplatelet agents from October 1, 2013, until January 31, 2015, with follow-up through June 30, 2018. Data were collected using the health care utilization database of Lombardy region in Italy. Data analysis was conducted from March to November 2020.Cohort members were followed up to identify those who discontinued statins. Among this group, those who maintained other therapies during the first 6 months after statin discontinuation were 1:1 propensity score matched with patients who discontinued neither statins nor other drugs.The pairs of patients discontinuing and maintaining statins were followed up from the initial discontinuation until June 30, 2018, to estimate the hazard ratios (HRs) and 95% CIs for fatal and nonfatal outcomes associated with statin discontinuation.The full cohort inclued 29 047 patients exposed to polypharmacy (mean [SD] age, 76.5 [6.5] years; 18 257 [62.9%] men). Of them, 5819 (20.0%) discontinued statins while maintaining other medications, and 4010 (68.9%) of them were matched with a comparator. In the discontinuing group, the mean (SD) age was 76.5 (6.4) years, 2405 (60.0%) were men, and 506 (12.6%) had Multisource Comorbidity Scores of 4 or 5. In the maintaining group, the mean (SD) age was 76.1 (6.3) years, 2474 (61.7%) were men, and 482 (12.0%) had multisource comorbidity scores of 4 or 5. Compared with the maintaining group, patients in the discontinuing group had increased risk of hospital admissions for heart failure (HR, 1.24; 95% CI, 1.07-1.43) and any cardiovascular outcome (HR, 1.14; 95% CI, 1.03-1.26), deaths from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.05-1.19).In this study of patients receiving polypharmacy, discontinuing statins while maintaining other drug therapies was associated with an increase in the long-term risk of fatal and nonfatal cardiovascular outcomes.
Clinical outcomes in metastatic renal cell carcinoma (mRCC) treated with combination of nivolumab and cabozantinib (nivo-cabo) in the salvage setting.
Authors: Deepak Ravindranathan, Yuan Liu, Dylan J. Martini, Bassel Nazha, Jacqueline T Brown, Greta Russler, Lauren Beth Yantorni, Sarah Caulfield, Viraj A. Master, Bradley Curtis Carthon, Omer Kucuk, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2021)

e16570 Background: The CheckMate 9ER trial showed that the combination of nivolumab and cabozantinib (nivo-cabo) in first line setting for treatment of mRCC was superior to sunitinib in terms of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) and led to its FDA approval. We report outcomes of cohort of patients with mRCC treated with nivo-cabo in the salvage setting. Methods: We retrospectively reviewed 17 patients with mRCC treated at Winship Cancer Institute who progressed through at least one line of prior therapy. These patients were then treated with either sequences: [1] cabozantinib and then add nivolumab upon progression (n = 8) and [2] nivolumab/ipilimumab or nivolumab and then add cabozantinib upon progression (n = 9) with two with nivolumab and ipilimumab. Median PFS and OS rates, and clinical benefit (defined as complete response or partial response, or stable disease) were described. Results: Thirteen patients had clear cell histology and four patients had non-clear cell histology. For sequence [1], the mPFS for cabozantinib alone was 9.9 months and combination of nivolumab added to cabozantinib was 8.9 months. For sequence [2], the mPFS for nivolumab with or without ipilimumab was 5.9 months and combination of cabozantinib added to nivolumab was 10.4 months. The 12-month OS rate was 88% for sequence [1] and 89% for sequence [2]. The 24-month, OS rate was 50% for sequence [1] and 89% for sequence [2]. 5/8 (63%) patients in sequence [1] and 7/9 (78%) patients in sequence [2] had clinical benefit. 3/8 (37.5%) patients in sequence [1] and 2/9 (22%) patients in sequence [2] experienced immune-related adverse effects such as hypothyroidism (grade II for two patients), pneumonitis (grade II), hepatic transaminase elevations (grade II), and pancreatitis (grade III). No patients in sequence [1] needed dose reduction in cabozantinib once nivolumab was added. 3/9 (33%) patients had dose reduction in cabozantinib in sequence [2] due to diarrhea. Conclusions: Nivo-cabo demonstrates activity in the salvage setting but there is still need to understand the optimal sequencing of both agents in the treatment of mRCC. Outcomes from this combination treatment are to be further validated from ongoing phase III trial, PDIGREE (NCT03793166).
Insurance data of patients receiving sequential immune checkpoint inhibitors: A single center experience.
Authors: Muhammad Awidi, Rojer Ranjit, Brendan James Connell, Brigitte Gil, Natalie Dalbo, Lewena Maher, Seanna Daves, Stephanie McDonald, Philip Tsoukas, Linda Voner, Krishna Soujanya Gunturu
Journal: Journal of Clinical Oncology (2021)

e18835 Background: Immune checkpoint inhibitors (ICI) up regulate T cell activity promoting tumor cell death and revolutionized modern oncology. The use and number of indications for ICI is growing at an unprecedented speed. Combination and sequential ICI therapies have been shown to be beneficial in certain types of cancer. There is no significant data to support non-FDA approved sequential use of ICI when patients develop toxicities or progression which could result in a significant financial burden on the patient and the health care system. We conducted a retrospective review of cancer patients receiving ICI at our institution and evaluated the insurance status of these patients who received sequential ICI. Methods: We retrospectively reviewed Oncology patients’ charts who received ICI between January 1, 2014 to December 18, 2018. We identified patients receiving sequential ICI, to be defined as patients who received a second ICI, following an initial ICI therapy. Insurance status was evaluated for patients receiving sequential therapy. Commercial insurance was defined as either private or non-Medicare/Medicaid. Results: Out of total 437 patients receiving ICI, 15 patients received sequential ICI. 11 patients were transitioned to a secondary ICI following disease progression (73%), three had immune related adverse events and one was switched per standard of care. Nine patients (60%) had commercial insurance and six patients (40%) had medicare/medicaid. Of those, one had urothelial carcinoma and was switched to pembrolizumab from atezolizumab due to disease progression. One patient had melanoma and received nivolumab following ipilimumab when data from the CHECKMATE 238 were published. Three patients with melanoma were transitioned from ipilimumab to nivolumab, two had disease progression and one had autoimmune dermatitis. Two patients had lung adenocarcinoma and were switched from nivolumab to pembrolizumab due to disease progression. One patient had small cell lung cancer and received pembrolizumab following nivolumab due to disease progression. One patient had squamous cell lung cancer and was switched to pembrolizumab from nivolumab following disease progression. Conclusions: With the rapid growth and advancement of ICI indications, there is limited data available on the benefits of sequential ICI to our patients in the clinical setting. We report a small percentage of oncology patients receiving sequential treatment with or without FDA approval and explore their insurance status. Majority of our patients who transitioned to a second ICI due to progression had commercial insurance. Larger prospective studies are needed to evaluate sequential ICI efficacy and tolerability and cost effectiveness.
Abstract 12450: Biological Pacemaker Created by HCN4-Overexpressing Human iPS Cell-Derived Cardiomyocytes
Authors: Kazufumi Nakamura, Yukihiro Saito, Masashi Yoshida, Kaoru Akazawa, Nobuhiro Nishii, Toru Miyoshi, Hiroshi Ito
Journal: Circulation (2018)

Background: Establishment of a biological pacemaker is expected to solve the persisting problems of a mechanical pacemaker including short battery life. Enhancement of the funny current (If) flowin...
Correction to: Expanding controlled donation after the circulatory determination of death: statement from an international collaborative
Authors: Beatriz Domínguez-Gil, Nancy Ascher, Alexander M. Capron, Dale Gardiner, Alexander R. Manara, James L. Bernat, Eduardo Miñambres, Jeffrey M. Singh, Robert J. Porte, James F. Markmann, Kumud Dhital, Didier Ledoux, Constantino Fondevila, Sarah Hosgood, Dirk Van Raemdonck, Shaf Keshavjee, James Dubois, Andrew McGee, Galen V. Henderson, Alexandra K. Glazier, Stefan G. Tullius, Sam D. Shemie, Francis L. Delmonico
Journal: Intensive Care Medicine (2021)

A correction to this paper has been published: https://doi.org/10.1007/s00134-021-06435-w
Multistate outbreak of monkeypox - Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003.
Authors: C. W. Langkop, C. Austin, M. Dworkin, K. Kelly, H. Messersmith, R. Teclaw, J. Howell, J. Michael, P. Pontones, G. Pezzino, G. R. Hansen, M. V. Wegner, J. J. Kazmierczak, C. Williams, D. R. Croft, S. Ahrabi-Fard, L. Will, H. H. Bostrom, J. P. Davis, A. Fleischauer, M. Sotir, G. Huhn, R. Kanwal, J. Kile, J. Sejvar
Journal: MMWR Morbidity and Mortality Weekly Report (2003)
Prevalence of lung cancer in Colombia and a new diagnostic algorithm using health administrative databases: A real-world evidence study.
Authors: Giancarlo Buitrago, Javier Amaya-Nieto, Gabriel Fernando Torres
Journal: Journal of Clinical Oncology (2021)

e18764 Background: Reliable, timely and detailed information of lung cancer mortality and costs from low- and middle-income countries is essential to policy design. We aimed to develop an electronic algorithm to identify lung cancer prevalent patient in Colombia using official databases and to estimate prevalence rates by age, sex, and geographic region. Methods: We performed a cross sectional study based on national claim databases in Colombia ( Base de datos de suficiencia de la Unidad de Pago por Capitación and Base de Datos Única de Afiliados) to identify lung cancer prevalent patients in 2017. Several algorithms based on the presence or absence of oncological procedures (Chemotherapy, radiotherapy and surgery), and a minimum number of months that each individual had lung cancer ICD-10 codes in the previous 3 years, were developed. After testing 16 algorithms, those with the closest prevalence rates to the ones reported by aggregated official sources (GLOBOCAN, National Cancer Institute and Cuenta de Alto Costo) were selected . We estimated prevalence rates by age, sex, and geographic region. Results: Two algorithm s were selected: i) it was defined as the presence of ICD-10 codes for 4 months or more (sensitive algorithm); and ii) adding the presence of at least one oncological procedure (specific algorithm). Estimated prevalence rates per 100,000 population were 15.3 and 9.7 for the sensitive and specific algorithms, respectively. These rates were higher in men (9.9), over 65 years old (37.1), who lived in Central and Bogota regions (14.7 and 10.9, respectively) (Table). Conclusions: Selected algorithms showed similar prevalence estimations to those reported by official sources and allowed us to estimate prevalence rates in specific aging, regional and gender groups for Colombia using national claims databases. These findings could be useful to identify clinical and economical outcomes related to lung cancer patients using national individual-level databases. [Table: see text]
HGG-15. THE IMIPRIDONE ONC201 IN COMBINATION WITH THE ONCOLYTIC ADENOVIRUS DELTA-24-RGD HAS A SYNERGISTIC EFFECT IN PRECLINICAL MODELS OF PHGGS AND DMGS
Authors: Daniel de la Nava, Iker Ausejo-Mauleon, Virginia Laspidea, Lucía Marrodán, Marta Zalacain, Guillermo Herrador-Cañete, Javad Nazarian, Sabine Mueller, Joshua E Allen, Juan Fueyo, Candelaria Gomez-Manzano, Sumit Gupta, Ana Patiño, Marta M Alonso
Journal: Neuro-Oncology (2021)

Abstract Pediatric High Grade Gliomas (pHGGs), including Diffuse Midline Gliomas (DMGs), are aggressive pediatric tumors with a poor overall survival. In the last years, ONC201 has emerged as a promising agent in the field of pediatric brain tumors. Another interesting approach is virotherapy; Delta-24-RGD, which is an oncolytic virus, has demonstrated safety and effectiveness in different preclinical models and in clinical trials. Therefore, in this work we set to evaluate whether the combination of ONC201 with Delta-24-RGD could result in an increased therapeutic benefit in pHGGs and DMGs. Given that ONC201 targets mitochondrial metabolism in a preclinical setting, we assessed potential negative interactions of the combination therapy. While ONC201 treatment resulted in decreased viral protein load (E1A and fiber), there was no significant negative impact on the viral replication (measured by hexon staining). ONC201 did not disrupt the activation of mTORC1 pathway by the adenovirus. Furthermore, Delta-24-RGD did not affect the decrease in basal oxygen consumption rate induced by ONC201. Our results suggested that ONC201 and Delta-24-RGD are not antagonistic. Evaluation of the in vitro cytotoxicity in different human pHGG (CHLA-03-AA and SF188) and DMG (TP-54 and SU-DIPG-IV) cell lines showed that the combination treatment was significantly better that either agent alone. In vivo, a single local injection of Delta-24-RGD followed by a weekly ONC201 of mice bearing CHLA-03-AA cell line orthotopically significantly increased the median overall survival (PBS: 48 days; ONC201: 54.5 days; Delta-24-RGD: 62 days; ONC201+Delta-24-RGD: 95 days (P=0.0008)) of these mice leading to 20% long-term survivors, free of disease. Currently, we are evaluating the effect of the combination in immunosuppressed and immunocompetent models of DMGs. In summary, our data indicate ONC201 in combination with Delta-24-RGD could be a potential therapeutic choice for patients affected by pHGGs and DMGs.
TMOD-06. LOSS OF DICER COOPERATES WITH TUMOR SUPPRESSORS TO INITIATE METASTATIC MEDULLOBLASTOMA
Authors: Sheila Alcantara Llaguno, Inga Nazarenko, Yuntao Chen, Daochun Sun, Gaspare La Rocca, Alicia Pedraza, Brian Gudenas, Olivier Saulnier, Dennis Burns, Tejus Bale, Paul Northcott, Michael Taylor, Andrea Ventura, Luis Parada
Journal: Neuro-Oncology (2021)

Abstract To determine the role of microRNA regulation in brain tumor development, we incorporated a conditional allele of the microRNA processing enzyme Dicer to a previously characterized glioma mouse model based on inactivation of the tumor suppressors Nf1, Trp53, and Pten using the Nestin-creERT2 transgene. Loss of Dicer and tumor suppressors at adult ages led to glioma development; however, mutant mice tamoxifen induced at early postnatal ages developed medulloblastoma instead of glioma. The switch in tumor spectrum occurred with 100% penetrance and tumors were histologically indistinguishable from human medulloblastoma (MB). The minimum genetic mutations required for MB formation were Dicer and Trp53. Nf1 was dispensable, while additional loss of Pten produced more invasive tumors and leptomeningeal metastases. The time window for initiation of tumorigenesis was until the 2nd postnatal week, coinciding with the disappearance of the external granule layer (EGL), where cerebellar granule neuron precursors (CGNPs) undergo proliferation. Analysis of pre-symptomatic mutant mice showed proliferative defects and retained cells in the EGL, suggesting that the tumors may arise from CGNPs. However, targeting a subset of CGNPs using Math1-creERT2 did not lead to MB development, suggesting that an earlier EGL precursor may be required for tumorigenesis. Analysis of tumor transcriptome and MB subtype-specific genes and markers show that Dicer tumors most resemble extremely high risk p53-mutated SHH MB. Small RNA and mRNA sequencing analyses showed downregulation of microRNAs and dysregulation of its targets such as N-Myc. These studies demonstrate a role for microRNAs in MB development and show a fully penetrant genetic mouse model of highly metastatic MB.