tbuckley/cabot-search huggingface dataset:
Broadened Eligibility for Lung Cancer Screening
Authors: Louise M. Henderson, M. Patricia Rivera, Ethan Basch
Journal: JAMA (2021)

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Multi-institutional evaluation of the clinical outcomes and genomic correlates of African Americans with metastatic castration-sensitive prostate cancer (mCSPC).
Authors: Meredith MI Freeman, Ellen Jaeger, Jason Zhu, Audrey Phone, Roberto Nussenzveig, Sydney Caputo, Deepak Ravindranathan, Jodi Lyn Layton, Lakshminarayanan Nandagopal, Adam Kessel, Arpita Desai, Vadim S Koshkin, Arnab Basu, Mehmet Asim Bilen, Umang Swami, Jorge A. Garcia, Neeraj Agarwal, Earle F Burgess, A. Oliver Sartor, Pedro C. Barata
Journal: Journal of Clinical Oncology (2021)

17 Background: Prostate cancer incidence and mortality is higher in African American (AA) as compared with non-AA men. The outcomes of mCSPC have significantly improved through treatment intensification yet, AA representation in those studies was suboptimal. We aimed to report the clinical, treatment outcomes and genomic data of AA men with mCSPC. Methods: Retrospective analysis of consecutive AA men with mCSPC at six Academic Institutions. The primary objective was to report the baseline characteristics and treatment patterns of mCSPC AA patients. The secondary objectives included the germline and somatic data and the clinical outcomes including PSA response, progression-free survival and subsequent treatments. Results: A total of 71 patients, median age 63 years (range, 41-84) with 58% Gleason 8-10, initial PSA of 69.8 ng/mL (0.02-7650), 59% with de-novo and 55% with high-volume (CHAARTED criteria; 20% visceral) disease, were included in this analysis. Twenty-two patients (31%) were treated with androgen deprivation therapy (ADT; 67% prior to year 2017), while 24%, 45% and 3% received docetaxel (median 6 cycles), abiraterone acetate and enzalutamide, respectively. Two patients received triplet therapy with ADT/docetaxel plus abiraterone or enzalutamide. Undetectable PSA was achieved in 35% after a median of 8.9 months (1.8-22.3). Among patients with mCSPC who received radiation therapy to prostate (n = 8), 89% had low volume disease. At time of cut off, thirty-two patients developed CRPC and the estimated median time to CRPC was 2.9 years (95% CI, 1.6-4.2). Subsequent therapies (n = 29) included abiraterone acetate (41%), enzalutamide (24%), bicalutamide (10%), radium-223 (7%), chemotherapy (7%), sipuleucel-T (3%) and others (7%). Five patients (8%) had pathogenic germline alterations (n = 2 BRCA1; n = 1 HOXB13, PALB2 and PMS2). Additionally, the most common somatic alterations among tested patients (n = 27) included CDK12, SPOP, TMPRSS2-ERG fusion, and TP53, all in 11% frequency. Of note, n = 2 BRCA1 and n = 1 high MSI/TMB. Conclusions: In one of the largest reported cohorts to our knowledge, mCSPC AA presented with a high number of de-novo and high-volume disease and might harbor a different germline and somatic genomic profile. The outcomes were comparable to contemporary phase III trials with treatment intensification, yet 31% were treated with ADT. Despite the known limitations associated with retrospective analysis, these data support prior observations where AA might have better initial PSA responses to ADT-based strategies compared with Caucasians, requiring further validation.
High-resolution T1 MRI via renally clearable dextran nanoparticles with an iron oxide shell
Authors: Tae-Hyun Shin, Pan Ki Kim, Sunghwi Kang, Jiyong Cheong, Soojin Kim, Yongjun Lim, Wookjin Shin, Joon-Yong Jung, Jungsu D. Lah, Byoung Wook Choi, Jinwoo Cheon
Journal: Nature Biomedical Engineering (2021)
Abstract 17265: Comparing Ultrasound Guided and Conventional Method of Venipuncture for Electrophysiological Procedures: A Meta-Analysis
Authors: Udit Joshi, Sisir Siddamsetti, Sagar Ranka, Harsh Rawal, Jai Parekh, Srikanth Yandrappalli, Vamsi Kodumuri
Journal: Circulation (2018)

Introduction: There has been steady increase in the number of catheter ablations for the definitive management of atrial fibrillation and it is associated with its own complications with vascular complications being the most common. There are many studies comparing Ultrasound (US) guided versus Conventional Method (CM) of venipuncture for complications as these patients are on therapeutic anticoagulation. We conducted a meta-analysis to look for any difference between the two approaches. Methods: PubMed, Medline, EMBASE and Cochrane databases were analyzed from inception to January 2018 for all studies comparing US vs CM for venipuncture in patients undergoing catheter ablation. Four observational studies and one Randomized Controlled Trial (RCT) with 5158 patients were studied for major and minor vascular complications. Major vascular complications included hematoma/major bleeding (more than or equal to BARC2), AV fistula and pseudo aneurysm. Random effect model was used to estimate the odds ratio of dichotomous outcomes Results: Major and minor vascular complications were significantly less with US guided approach as compared to conventional approach {Odds Ratio (OR): 0.36, 95% CI 0.21-0.61, P=0.0002} and {Odds Ratio (OR): 0.30, 95% CI 0.15-0.64, P=0.002} respectively. Conclusion: Real time ultrasound use for venipuncture access is safer approach with significantly lesser vascular complications in patients with atrial fibrillation on anticoagulation undergoing catheter ablation.
Abstract PR006: Infiltration of TRPV1+ nerves influences the ovarian cancer immune landscape
Authors: Hunter D. Reavis, Daniel W. Vermeer, Anthony C. Restaino, Allison Kruse, Matthew Knarr, Paola D. Vermeer, Ronny Drapkin
Journal: Cancer Research (2021)

Abstract High-grade serous ovarian carcinoma (HGSC) is the most lethal gynecological malignancy, with poor survival rates attributable to both late diagnosis and resistance of tumors to standard-of-care chemotherapies. Recent therapeutic strategies aim to circumvent chemoresistance by targeting tumor-extrinsic factors that support the tumor microenvironment (TME). While TME-targeted therapies such as immunotherapy and anti-angiogenics have shown promise in other chemoresistant disease states, no substantial benefit has been observed in HGSC. We have recently observed that HGSC tumors are densely infiltrated by transient receptor potential vanilloid 1 (TRPV1+) sensory nerves that are otherwise absent in normal gynecological tissues. Tumor innervation has been shown to correlate with poor prognostic outcomes in other solid tumor types and thus warrants investigation in the context of HGSC. Our preliminary data using a syngeneic mouse model of HGSC shows that diphtheria toxin-mediated ablation of TRPV1+ nerves (Trpv1-DTA) attenuates HGSC tumor growth in vivo. Furthermore, preliminary immunohistochemical analysis of HGSC tumors from wild-type versus Trpv1-DTA mice has revealed differential infiltration of immune cell populations, indicating that tumor innervation may influence immunoreactivity within the TME. These results provide us with a basis for understanding how therapeutic targeting of tumor infiltrating nerve populations may sensitize HGSC tumors to immunotherapy. Citation Format: Hunter D. Reavis, Daniel W. Vermeer, Anthony C. Restaino, Allison Kruse, Matthew Knarr, Paola D. Vermeer, Ronny Drapkin. Infiltration of TRPV1+ nerves influences the ovarian cancer immune landscape [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PR006.
Association of Supporting Trial Evidence and Reimbursement for Off-Label Use of Cancer Drugs
Authors: Amanda Katherina Herbrand, Andreas M. Schmitt, Matthias Briel, Hannah Ewald, Marius Goldkuhle, Stefan Diem, Anouk Hoogkamer, Markus Joerger, Giusi Moffa, Urban Novak, Lars G. Hemkens, Benjamin Kasenda
Journal: JAMA Network Open (2021)

<h3>Importance</h3> In many health systems, access to off-label drug use is controlled through reimbursement restrictions by health insurers, especially for expensive cancer drugs. <h3>Objective</h3> To determine whether evidence from randomized clinical trials is associated with reimbursement decisions for requested off-label use of anticancer drugs in the Swiss health system. <h3>Design, Setting, and Participants</h3> This cross-sectional study used reimbursement requests from routinely collected health records of 5809 patients with drug treatment for cancer between January 2015 and July 2018 in 3 major cancer centers, covering cancer care of approximately 5% of the Swiss population, to identify off-label drug use. For each off-label use indication with 3 or more requests, randomized clinical trial evidence on treatment benefits was systematically identified for overall survival (OS) or progression-free survival (PFS). Data were analyzed from August 2018 to December 2020. <h3>Exposures</h3> Available randomized clinical trial evidence on benefits for OS or PFS for requested off-label use indications. <h3>Main Outcomes and Measures</h3> The main outcome was the association between evidence for treatment benefit (expressed as improved OS or PFS) and reimbursement in multivariable regression models. <h3>Results</h3> Among 3046 patients with cancer, 695 off-label use reimbursement requests in 303 different indications were made for 598 patients (median [interquartile range] age, 64 [53-73] years; 420 [60%] men). Off-label use was intended as first-line treatment in 311 requests (45%). Reimbursement was accepted in 446 requests (64%). For 71 indications, including 431 requests for 376 patients, there were 3 or more requests. Of these, 246 requests (57%) had no supporting evidence for OS or PFS benefit. Reimbursement was granted in 162 of 246 requests without supporting evidence (66%). Of 117 requests supported by OS benefit, 79 (67%) were reimbursed, and of 68 requests supported by PFS benefit alone, 54 (79%) were reimbursed. Evidence of OS benefit from randomized clinical trials was not associated with a higher chance of reimbursement (odds ratio, 0.76, 95% CI, 0.45-1.27). <h3>Conclusions and Relevance</h3> These findings suggest that in a health care system enabling access to off-label use, it was frequently intended as a first-line treatment in cancer care. Availability of randomized clinical trial evidence showing survival benefit was not associated with reimbursement decisions for off-label anticancer drug treatment in Switzerland. A transparent process with criteria considering clinical evidence is needed for evidence-based reimbursement decisions to ensure fair access to cancer treatments.
Abstract 12948: ALP Levels Predict Adverse Cardiovascular Outcomes and Cognitive Impairment in High Risk Patients
Authors: Kausik K Ray, Jeffrey L Cummings, Mathias L Haarhaus, Peter P Toth, Stephen Nicholls, Henry N Ginsberg, Bengt Winblad, Henrik Zetterberg, Michael Sweeney, Jan O Johansson, Ewelina Kulikowski, Kenneth Lebioda, Aziz Khan, Christopher Halliday, Carmine Zoccali, Kamyar Kalantar-Zadeh, Gregory G Schwartz
Journal: Circulation (2019)

Background: Serum alkaline phosphatase (ALP) is associated with incident cardiovascular disease (CVD), coronary artery disease, vascular calcification, cerebral small vessel disease and ischemic st...
Particulate Matter and Cardiovascular Risk in Adults with Chronic Obstructive Pulmonary Disease
Authors: Stacey E. Alexeeff, Kamala Deosaransingh, Noelle S. Liao, Stephen K. Van Den Eeden, Joel Schwartz, Stephen Sidney
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: People with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease and may be more susceptible to air pollution exposure. However, no study has examined the association between long-term fine particulate matter exposure (≤2.5 μm in aerodynamic diameter) and risk of cardiovascular events in this potentially vulnerable population. Objectives: To estimate the association between long-term fine particulate matter and risk of cardiovascular events among adults with COPD. Methods: This retrospective cohort study included 169,714 adults with COPD who were members of the Kaiser Permanente Northern California health plan during 2007–2016. Electronic health record data were linked to 1 km modeled particulate matter ≤2.5 μm in aerodynamic diameter exposure estimates. We fit Cox proportional hazard models, adjusting for age, sex, race/ethnicity, calendar year, smoking, body mass index, comorbidities, medications, and socioeconomic status. In low exposure analyses, we examined effects below the current regulation limit (12 μg/m3). Measurements and Main Results: Among adults with COPD, a 10-μg/m3 increase in 1-year mean fine particulate matter exposure was associated with an elevated risk of cardiovascular mortality (hazard ratio, 1.10; 95% confidence interval [CI], 1.01–1.20). Effects were stronger in low exposure analyses (hazard ratio, 1.88; 95% CI, 1.56–2.27). Fine particulate matter exposure was not associated with acute myocardial infarction or stroke in overall analyses. Conclusions: Long-term fine particulate matter exposure was associated with an increased risk of cardiovascular mortality among adults with COPD. Current regulations may not sufficiently protect those with COPD.
Racial Disparities in Diagnosis of Attention-Deficit/Hyperactivity Disorder in a US National Birth Cohort
Authors: Yu Shi, Lindsay R. Hunter Guevara, Hayley J. Dykhoff, Lindsey R. Sangaralingham, Sean Phelan, Michael J. Zaccariello, David O. Warner
Journal: JAMA Network Open (2021)

<h3>Importance</h3> There are limited data on the racial disparities in the incidence of attention-deficit/hyperactivity disorder (ADHD) diagnosis in children at the national level. <h3>Objective</h3> To explore differences in rates of diagnosis of ADHD and use of treatment among children by race and ethnicity. <h3>Design, Setting, and Participants</h3> This retrospective cohort study assessed insurance claims data of children born in the US between January 1, 2006, and December 31, 2012, who had continuous insurance coverage for at least 4 years. The last date of follow-up included in the cohort was June 30, 2019. Race/ethnicity designations were based on self-report and included non-Hispanic White, Black, Hispanic, and Asian. Data were analyzed between October 2019 and December 2020. <h3>Exposures</h3> Race and ethnicity. <h3>Main Outcomes and Measures</h3> ADHD diagnosis as defined by<i>International Classification of Diseases</i>codes (ninth or tenth editions) and treatment within 1 year of diagnosis, including medication and behavior therapy as defined by billing codes. Data on ADHD diagnosis and treatment were adjusted for sex, region, and household income in a multivariate Cox regression model. <h3>Results</h3> Among 238 011 children in the cohort (116 093 [48.8%] girls; 15 183 [6.7%] Asian, 14 792 [6.2%] Black, 23 358 [9.8%] Hispanic, and 173 082 [72.7%] White children), 11 401 (4.8%) were diagnosed with ADHD. The cumulative incidence at age 12 was 13.12% (95% CI, 12.79%-13.46%). In multivariate Cox regression adjusting for sex, region, and household income, the hazard ratio for Asian children was 0.48 (95% CI, 0.43-0.53); Black children, 0.83 (95% CI, 0.77-0.90); and Hispanic children, 0.77 (95% CI, 0.72, 0.82) compared with White children. In the first year after diagnosis, 516 preschool children (19.4%) received behavioral therapy only, 860 (32.4%) had medications only, 505 (19.0%) had both, and 774 (29.2%) had no claims associated with either option. A higher percentage of school-aged children (2904 [65.6%]) were prescribed medications, and fewer had therapy only (639 [14.4%]) or no treatment at all (884 [20.0%]). Compared with other groups, White children were more likely to receive some kind of treatment. Asian children had the highest odds of receiving no treatment (odds ratio compared with White children, 0.54; 95% CI, 0.42-0.70). <h3>Conclusions and Relevance</h3> Racial and ethnic disparities in the diagnosis and treatment of ADHD are evident. Future study is needed to elucidate the mechanism behind these disparities, with special attention to Asian children. Clinicians should provide racially sensitive care in the evaluation and treatment of ADHD.
PSA velocity to predict clinical progression in African American and non-Hispanic White patients with low-risk prostate cancer undergoing active surveillance.
Authors: Juan Javier-Desloges, Tyler Nelson, Patrick Travis Courtney, Rishi Deka, Vinit Nalawade, Loren K. Mell, James Don Murphy, J Kellogg Parsons, Brent S. Rose
Journal: Journal of Clinical Oncology (2021)

196 Background: The utility of prostate-specific antigen velocity (PSAV) to predict clinical progression in patients with localized prostate cancer (PC) on active surveillance remains unclear, and in African American (AA) patients on active surveillance remains undefined. Methods: We performed a cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure (VINCI). We identified 5296 patients diagnosed with localized prostate cancer (PC) from 2001 to 2015 managed with active surveillance. Follow-up extended through March 31, 2020. We defined low-risk PC as ISUP grade group 1 (GG1) clinical tumor stage ≤ 2A, and PSA level ≤ 10 ng/dl; and active surveillance as no definitive treatment within the first year after diagnosis with at least one additional staging biopsy after diagnostic biopsy. The primary outcome was grade progression on repeat biopsy/prostatectomy defined as GG2 or GG3. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards models were used to test associations between PSAV and outcomes. Results: The final cohort included 3919 Non-Hispanic White patients (NHW) (74%) and 1377 AA (26%) patients. GG2 progression on repeat biopsy occurred in 2062 (38.9%) patients, with a cumulative incidence (CI) of 43.2 % and GG3 progression occurred in 728 (13.7%) patients, with a CI of 18% at seven years. Fifty-four (0.8%) patients developed metastases, with a CI of 1.4% at ten years. In unadjusted analyses, compared to NHW patients, AA patients were significantly more likely to progress to GG2 (52.8% vs 39.8%, p&lt;0.001), and GG3 (22.2% vs 16.8%, p=0.01). On MV analysis, PSAV was a significant predictor of GG2 (HR 1.32 [1.26-1.39]), GG3 (1.5 [1.40-1.62]), and metastases (1.38 [1.10-1.74]). A significant interaction term between race and PSAV indicated the need for different PSAV thresholds for AA and NHW men. Based on maximally selected rank statistics, optimal thresholds for separating outcomes were different in AA vs NHW men. (0.44 vs. 1.18). Conclusions: In this analysis of PSAV in low-risk prostate cancer patients on AS—to our knowledge, the largest to date for AA patients—we observed that PSAV is a robust predictor of upgrading on restaging biopsy as well as metastasis. Compared to NHW patients, AA patients were more likely to progress at lower values of PSAV and therefore merit close follow-up on active surveillance protocols.
Abstract 676: HDLc and ApoB-Particle Benefits in Metabolic Syndrome Patients From a Selective PPARdelta Agonist (GW501516): Mechanism Beyond Peripheral Metabolism Alone
Authors: Eric J Olson, Dennis L Sprecher, Nigel P Jones, Joanna U Segieth, Greg Pearce
Journal: Circulation (2007)

A predominant PPARdelta-induced upregulation in skeletal muscle fatty acid oxidation, would predict modulation of lipid/lipoproteins based on associated serum free fatty acid (FFA) levels. Lipid/li...
Darks and Lights, the ‘Yin–Yang’ of Vision Depends on Luminance
Authors: Dirk Jancke
Journal: Trends in Neurosciences (2021)

We all know the disappointment when, after a wonderful snapshot, the details in the photo are at much lower contrast than seen before with our own eyes. A recent study by Rahimi-Nasrabadi et al. revealed that this is because human vision accounts for actual luminance range and for accompanied asymmetric changes in dark and light contrasts.
Long-term safety and efficacy of givinostat in polycythemia vera: 4-year mean follow up of three phase 1/2 studies and a compassionate use program
Authors: Alessandro Rambaldi, Alessandra Iurlo, Alessandro M. Vannucchi, Bruno Martino, Attilio Guarini, Marco Ruggeri, Nikolas von Bubnoff, Marianna De Muro, Mary Frances McMullin, Stefania Luciani, Vincenzo Martinelli, Axel Nogai, Vittorio Rosti, Alessandra Ricco, Paolo Bettica, Sara Manzoni, Silvia Di Tollo
Journal: Blood Cancer Journal (2021)

Abstract Polycythemia vera (PV) is a BCR-ABL1 -negative myeloproliferative neoplasm (MPN) characterized by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow, mainly due to a Janus kinase 2 gene mutation ( JAK2 V617F ). Givinostat, a histone-deacetylase inhibitor that selectively targets JAK2 V617F cell growth, has demonstrated good efficacy and safety in three phase 1/2 studies in patients with PV. This manuscript focuses on the 4-year mean (2.8 year median) follow-up of an open-label, long-term study that enrolled 51 patients with PV (out of a total of 54 with MPN) who received clinical benefit from givinostat in these previous studies or on compassionate use, and who continued to receive givinostat at the last effective and tolerated dose. The primary objectives are to determine givinostat’s long-term safety and tolerability, and efficacy evaluated by the investigators according to internationally recognized response criteria. During follow-up, only 10% of PV patients reported Grade 3 treatment-related adverse events (AEs), while none had Grade 4 or 5 treatment-related AEs. The overall response rate for the duration of follow-up was always greater than 80% in patients with PV. In conclusion, givinostat demonstrated a good safety and efficacy profile in patients with PV, data supporting long-term use in this population.