tbuckley/cabot-search huggingface dataset:
Comparative effectiveness of short contact (30-minute) lidocaine-prilocaine vs lidocaine-tetracaine topical anesthetic mixtures for cutaneous pain relief: A randomized controlled trial
Authors: Eric Koza, Melanie Clark, Areeba Ahmed, Melissa S. Ma, Victoria J. Shi, Misha Haq, Alexandra Weil, Amanda Maisel-Campbell, Sanjana Iyengar, Emily Poon, Brian A. Cahn, Ross Pearlman, Daniel Schlessinger, Murad Alam
Journal: Journal of the American Academy of Dermatology (2024)
Simulating the population impact of interventions to reduce racial gaps in breast cancer treatment
Authors: Juan Yanguela, Bradford E Jackson, Katherine E Reeder-Hayes, Mya L Roberson, Gabrielle B Rocque, Tzy-Mey Kuo, Matthew R LeBlanc, Christopher D Baggett, Laura Green, Erin Laurie-Zehr, Stephanie B Wheeler
Journal: JNCI Journal of the National Cancer Institute (2024)

Inequities in guideline-concordant treatment receipt contribute to worse survival in Black patients with breast cancer. Inequity-reduction interventions (eg, navigation, bias training, tracking dashboards) can close such treatment gaps. We simulated the population-level impact of statewide implementation of inequity-reduction interventions on racial breast cancer inequities in North Carolina.
NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport
Authors: Sen Yang, Zhen-Xian Niou, Andrea Enriquez, Jacob LaMar, Jui-Yen Huang, Karen Ling, Paymaan Jafar-Nejad, Jonathan Gilley, Michael P. Coleman, Jason M. Tennessen, Vidhya Rangaraju, Hui-Chen Lu
Journal: Molecular Neurodegeneration (2024)

Abstract Background Bioenergetic maladaptations and axonopathy are often found in the early stages of neurodegeneration. Nicotinamide adenine dinucleotide (NAD), an essential cofactor for energy metabolism, is mainly synthesized by Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) in CNS neurons. NMNAT2 mRNA levels are reduced in the brains of Alzheimer’s, Parkinson’s, and Huntington’s disease. Here we addressed whether NMNAT2 is required for axonal health of cortical glutamatergic neurons, whose long-projecting axons are often vulnerable in neurodegenerative conditions. We also tested if NMNAT2 maintains axonal health by ensuring axonal ATP levels for axonal transport, critical for axonal function. Methods We generated mouse and cultured neuron models to determine the impact of NMNAT2 loss from cortical glutamatergic neurons on axonal transport, energetic metabolism, and morphological integrity. In addition, we determined if exogenous NAD supplementation or inhibiting a NAD hydrolase, sterile alpha and TIR motif-containing protein 1 (SARM1), prevented axonal deficits caused by NMNAT2 loss. This study used a combination of techniques, including genetics, molecular biology, immunohistochemistry, biochemistry, fluorescent time-lapse imaging, live imaging with optical sensors, and anti-sense oligos. Results We provide in vivo evidence that NMNAT2 in glutamatergic neurons is required for axonal survival. Using in vivo and in vitro studies, we demonstrate that NMNAT2 maintains the NAD-redox potential to provide “on-board” ATP via glycolysis to vesicular cargos in distal axons. Exogenous NAD + supplementation to NMNAT2 KO neurons restores glycolysis and resumes fast axonal transport. Finally, we demonstrate both in vitro and in vivo that reducing the activity of SARM1, an NAD degradation enzyme, can reduce axonal transport deficits and suppress axon degeneration in NMNAT2 KO neurons. Conclusion NMNAT2 ensures axonal health by maintaining NAD redox potential in distal axons to ensure efficient vesicular glycolysis required for fast axonal transport.
Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis
Authors: Michael H. Le, David M. Le, Thomas C. Baez, Hansen Dang, Vy H. Nguyen, KeeSeok Lee, Christopher D. Stave, Takanori Ito, Yuankai Wu, Yee Hui Yeo, Fanpu Ji, Ramsey Cheung, Mindie H. Nguyen
Journal: Clinical and Molecular Hepatology (2024)

Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events.
Single-cell analysis of immune and stroma cell remodeling in clear cell renal cell carcinoma primary tumors and bone metastatic lesions
Authors: Shenglin Mei, Adele M. Alchahin, Ioanna Tsea, Youmna Kfoury, Taghreed Hirz, Nathan Elias Jeffries, Ting Zhao, Yanxin Xu, Hanyu Zhang, Hirak Sarkar, Shulin Wu, Alexander O. Subtelny, John Inge Johnsen, Yida Zhang, Keyan Salari, Chin-Lee Wu, Mark A. Randolph, David T. Scadden, Douglas M. Dahl, John Shin, Peter V. Kharchenko, Philip J. Saylor, David B. Sykes, Ninib Baryawno
Journal: Genome Medicine (2024)

Abstract Background Despite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets. Methods We collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue ( Bone Met ), liquid bone marrow at the vertebral level of spinal cord compression ( Involved ), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field ( Distal ), as well as bone marrow from patients undergoing hip replacement surgery ( Benign ). In addition, we incorporated single-cell data from primary ccRCC tumors ( ccRCC Primary ) for comparative analysis. Results The bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption. Conclusions These results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels.
Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression
Authors: Sumin Oh, Yang-Hyun Baek, Sungju Jung, Sumin Yoon, Byeonggeun Kang, Su-hyang Han, Gaeul Park, Je Yeong Ko, Sang-Young Han, Jin-Sook Jeong, Jin-Han Cho, Young-Hoon Roh, Sung-Wook Lee, Gi-Bok Choi, Yong Sun Lee, Won Kim, Rho Hyun Seong, Jong Hoon Park, Yeon-Su Lee, Kyung Hyun Yoo
Journal: Clinical and Molecular Hepatology (2024)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
European cancer mortality predictions for the year 2024 with focus on colorectal cancer
Authors: C. Santucci, S. Mignozzi, M. Malvezzi, P. Boffetta, G. Collatuzzo, F. Levi, C. La Vecchia, E. Negri
Journal: Annals of Oncology (2024)

We predicted cancer mortality figures for 2024 for the European Union (EU), its five most populous countries, and the UK. We focused on mortality from colorectal cancer (CRC).
The Effect of Practitioner Empathy on Patient Satisfaction
Authors: Leila Keshtkar, Claire D. Madigan, Andy Ward, Sarah Ahmed, Vinay Tanna, Ismail Rahman, Jennifer Bostock, Keith Nockels, Wen Wang, Clare L. Gillies, Jeremy Howick
Journal: Annals of Internal Medicine (2024)

Practitioners who deliver enhanced empathy may improve patient satisfaction with care. Patient satisfaction is associated with positive patient outcomes ranging from medication adherence to survival.
Large Language Models in Medicine: The Potentials and Pitfalls
Authors: Jesutofunmi A. Omiye, Haiwen Gui, Shawheen J. Rezaei, James Zou, Roxana Daneshjou
Journal: Annals of Internal Medicine (2024)

Large language models (LLMs) are artificial intelligence models trained on vast text data to generate humanlike outputs. They have been applied to various tasks in health care, ranging from answering medical examination questions to generating clinical reports. With increasing institutional partnerships between companies producing LLMs and health systems, the real-world clinical application of these models is nearing realization. As these models gain traction, health care practitioners must understand what LLMs are, their development, their current and potential applications, and the associated pitfalls in a medical setting. This review, coupled with a tutorial, provides a comprehensive yet accessible overview of these areas with the aim of familiarizing health care professionals with the rapidly changing landscape of LLMs in medicine. Furthermore, the authors highlight active research areas in the field that promise to improve LLMs' usability in health care contexts.
Trends in Discharge Rates for Acute Pulmonary Embolism in U.S. Emergency Departments
Authors: Nathan W. Watson, Brett J. Carroll, Anna Krawisz, Alec Schmaier, Eric A. Secemsky
Journal: Annals of Internal Medicine (2024)

Outpatient management of select patients with low-risk acute pulmonary embolism (PE) has been proven to be safe and effective, yet recent evidence suggests that patients are still managed with hospitalization. Few studies have assessed contemporary real-world trends in discharge rates from U.S. emergency departments (EDs) for acute PE.
Racial disparities in genitourinary cancer mortality trends in the United States, 2000-2020: A CDC database study.
Authors: Abdul Rahman Al Armashi, Marisa Thierheimer, Jorge A. Garcia, Jason R Brown
Journal: Journal of Clinical Oncology (2024)

28 Background: Prostate, bladder, and kidney cancers account for substantial burden of cancer incidence and mortality in the United States. In 2020, an estimated 168,000 new cases and 32,000 deaths were attributed to these cancers. Studies examining racial disparities of mortality trends are needed. Methods: We utilized the CDC WONDER database to obtain mortality data for kidney, bladder, and prostate cancers between 2000-2020. Age-adjusted mortality rates per 100,000 persons were calculated and standardized to the Year 2000 US standard population. Rates were stratified by race, including White, Black, Asian/Pacific Islander (API), and American Indian/Alaska Native (AIAN). The National Cancer Institute Joinpoint Regression Program was utilized to calculate average annual percent changes (AAPCs). AAPCs were considered significant if the 95% confidence interval (CI) excluded zero. Results: Over the study period, 318,919 kidney cancer deaths, 150,613 bladder cancer deaths, and 516,508 prostate cancer deaths were identified. Between 2000-2020, amongst all races, mortality from prostate cancer (-1.8%; CI -2.0, -1.6), bladder cancer (-0.3%; CI -0.5, -0.2), and kidney cancer (-1.1%; CI -1.2, -0.9) all significantly declined. Considering racial disparities, prostate cancer mortality fell considerably in all race groups, most significantly among Black (-2.8%, CI -3.2%, -2.4%) and AIAN (-2.4%, CI -2.9%, -1.8%) populations, outpacing reductions in API (-1.7%, CI -2.6%, -0.8%) and White (-1.6%, CI -1.9%, -1.4%) populations. In bladder cancer, the decline in mortality was statistically significant for Black (AAPC: -0.8%, CI -1.1%, -0.6%) and for White, (-0.4%, CI -0.6%, -0.1%), but not for API individuals (-0.3%, CI -0.9%, 0.3%). For kidney cancer, mortality dropped substantially across all examined races, with the steepest decline seen in Black (-1.4%, CI -1.7%, -1.2%) and AIAN (-1.7%, CI -2.5%, -1.0%) compared to White (-1.0%, CI -1.2%, -0.9%) and API (-1.4%, CI -4.2%, 1.6%, non-significant) population. Conclusions: This study represents the most comprehensive population database analysis assessing GU cancer mortality trends. While an overall decline in GU cancer mortality was observed, which was comparatively greater for Black Americans over the past two decades, significant racial disparities continue to persist. Focused and targeted efforts are essential to address these disparities. [Table: see text]
Impact of race on outcomes to 177Lu-PSMA-617 (LuPSMA) for metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Avina Rami, Thomas SC Ng, Emily Rothmann, Hailey Stoltenberg, Andrew Wolanski, Jolivette Ritzer, Atish Dipankar Choudhury, Xin Gao, Veronica Haberman, Bashar Kako, Kerry L. Kilbridge, Alicia K. Morgans, Aileen O'Shea, Mary-Ellen Taplin, Heather Jacene, Praful Ravi
Journal: Journal of Clinical Oncology (2024)

27 Background: Prior work suggests that African American (AA) and other minority patients (pts) derive equal benefit from taxane chemotherapy and androgen receptor pathway inhibitors (ARPIs) for mCRPC as white pts. LuPSMA showed an overall survival (OS) benefit in mCRPC pts after prior taxane and ARPI. However, there are no data on racial differences in outcomes to LuPSMA. Methods: We queried an IRB-approved registry of all pts treated with at least 2 cycles of LuPSMA between June 2022 and August 2023 at two academic medical centers in Boston, MA. Clinical data, including self-reported race, was abstracted from the electronic medical record. Pts of AA, Hispanic/Latino and Asian race were categorized as minorities. Outcomes of interest were the proportion of patients with ≥50% decrease in PSA levels during LuPSMA therapy (PSA50) and OS, defined from the date of the first cycle of LuPSMA. PSA50 and OS between races were compared with the Chi-Square and log-rank tests, respectively. Results: A total of 156 pts were included. Median age at LuPSMA initiation was 73 years (range 53-92) and the median number of prior lines of therapy was 5 (range 2-12); all pts had received ≥1 taxane and ≥1 ARPI. 136 (87%), 10 (6%), 6 (4%) and 4 (3%) pts were White, AA, Hispanic/Latino and Asian, respectively. The median number of LuPSMA cycles received in the entire cohort was 4 (range 2-7), and median follow-up was 7.1 months. A numerically higher proportion of minority pts had visceral disease at baseline compared to White pts (50% vs. 31%, (X 2 = 2.87, p=0.090). Overall, 86 pts (55%) had a PSA50, with PSA50 of 55% (n=75), 60% (n=6), 67% (n=4) and 25% (n=1) amongst White, AA, Hispanic/Latino and Asian pts, respectively. There was no significant difference in PSA50 between White and minority pts (X 2 = 0.00, p=0.990). Median OS in the entire cohort was 12.9 months and was not significantly different between White and minority pts (12.9 months vs. 8.5 months, p=0.533). The Table summarizes outcomes by race. Conclusions: PSA50 and OS were comparable between minority and White pts receiving LuPSMA for mCRPC, despite minority pts tending to present with more visceral disease, a known adverse prognostic factor. Validation of these findings and efforts to widen access to LuPSMA amongst minorities are required, given that pts of all racial backgrounds appear to benefit equally from LuPSMA. [Table: see text]
The frequency of use and enrollment impact of patient-centered outcomes in prostate cancer clinical trials.
Authors: Madison Krischak, Merrick Bank, Mary Byrnes, Kristian Stensland
Journal: Journal of Clinical Oncology (2024)

115 Background: Cancer treatments should help patients live either longer or better by improving patient quantity or quality of life. However, some trial endpoints do not correlate with overall survival, and are not noticeable to patients. Selecting endpoints for clinical trials that reflect these goals could improve the discovery process by ensuring trial results are of direct interest to patients, and perhaps by improving enrollment rates to trials. However, how frequently prostate cancer clinical trials use patient-centered outcomes, and how outcome type impacts trial enrollment, is unknown. Methods: On October 23, 2022, we queried ClinicalTrials.gov for full text records of phase 2-3 prostate cancer trials started after January 1, 2007. We extracted primary outcomes and other trial characteristics using a custom Python script. Two reviewers categorized each outcome into categories (e.g., overall survival, response rate, patient reported measure). As previously studied, the only valid surrogate for overall survival is metastasis-free survival. We considered these two outcomes or any outcome directly noticeable to a patient to be a patient-centered outcome. For completed or terminated trials, we defined ‘sufficient accrual’ as attaining 85% of a trial’s goal enrollment. We identified associations between trial outcome types and sufficient trial enrollment with chi-square tests and logistic regression. Results: Of 1,717 prostate cancer trials, only 37% used a patient-centered outcome, with 6% using overall or metastasis-free survival. Among 318 Phase 3 trials, 49% used a patient-centered outcome and 26% used overall or metastasis-free survival. Of 731 completed or terminated prostate cancer trials, 55% of trials and 68% of phase 3 trials reached sufficient enrollment (85% of enrollment goal). On multivariable analysis, trials with an overall survival endpoint had higher odds of sufficient enrollment (OR 8.0 [95% CI 2.2-33.5], p &lt; 0.01), but trials with any patient-centered outcome had lower odds of sufficient enrollment (OR 0.25 [95% CI 0.11-0.54], p &lt; 0.01). Conclusions: Less than half of prostate cancer trials use an outcome that is clearly patient-centered (i.e., affecting overall survival or an outcome noticeable to a patient). Further work is needed to clarify the use, understanding, and effect of outcome selection in cancer trials. Realigning trial efforts with patient-centered goals could improve the efficiency, productivity, and applicability of clinical trials.
Circulating tumor DNA in the surveillance of patients with oligometastatic renal cell carcinoma treated with stereotactic ablative radiation.
Authors: Young Suk Suk Kwon, Laurentiu Pop, Maggie Janell Stein, Alana Christie, Subrata Manna, Aurelie Garant, Daniel X. Yang, Neil B Desai, James Brugarolas, Robert D. Timmerman, Raquibul Hannan
Journal: Journal of Clinical Oncology (2024)

477 Background: Oligometastatic renal cell carcinoma (oRCC) patients receiving stereotactic ablative radiation (SAbR) are in need of effective biomarkers beyond imaging to identify those most likely to fail rapidly and therefore would benefit from systemic therapy. Detection of minimal residual disease (MRD) using circulating tumor (ctDNA) is a promising tool to guide decisions in the management of solid tumors. Herein, we investigate the utility of longitudinal ctDNA monitoring to identify high-risk patients. Methods: Patients with oRCC on surveillance after previous SAbR were enrolled in a prospective registry study and longitudinal quantitative ctDNA testing were performed using a tumor-informed commercial ctDNA assay (Signatera). Disease progression was assessed using standard-of-care clinical / radiographic exams and compared to the ctDNA levels that were obtained within the median 32.5 days (IQR 18.5-59) of radiographic exams. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. Results: The cohort encompassed 17 patients with oRCC (16/17 metachronous &gt;1 year after nephrectomy) who underwent 42 ctDNA measurements between September 2022 and August 2023 with a median of 3 (range 2-6) ctDNA time points per patient. Median follow up after start of ctDNA monitoring was 10.3 months. Seven patients developed radiographic progression at new sites including 6 who received additional SAbR and one who started systemic therapy with interleukin-2. At most recent follow up, 13/17 patients had no radiographic evidence of disease. Out of the 42 ctDNA time points, 11 had detectable ctDNA and 17 had clinical/radiographically detectable metastasis. The sensitivity, specificity, PPV, and NPV were calculated to be 64.7%, 100.0%, 100.0%, and 80.6% respectively. Out of 6 patients who underwent had ctDNA testing on SAbR, 5 had undetectable levels and the only patient that had detectable ctDNA levels showed a robust decline in ctDNA levels post SAbR. In the interleukin-2 treated patient, detectable levels of ctDNA became undetectable post treatment which also correlated with a complete radiographic response. Conclusions: This study highlights the utility of ctDNA as a prognostic biomarker in the surveillance of oRCC patients who were previously treated with SAbR. A high SPE and PPV suggests that rising ctDNA levels may harbinger radiographic progression requiring systemic therapy intervention. A larger study is warranted to further validate the findings of this study and to optimally integrate ctDNA kinetics to direct subsequent treatment choices for the oRCC patients.