tbuckley/cabot-search huggingface dataset:
Intratumoral Escherichia Is Associated With Improved Survival to Single-Agent Immune Checkpoint Inhibition in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Arielle Elkrief, Meagan Montesion, Smruthy Sivakumar, Caryn Hale, Anita S. Bowman, Ayyüce Begüm Bektaş, Martina Bradic, Wenfei Kang, Eric Chan, Pooja Gogia, Katia Manova-Todorova, Douglas A. Mata, Jacklynn V. Egger, Hira Rizvi, Nicolas D. Socci, Daniel W. Kelly, Eric Rosiek, Fanli Meng, Grittney Tam, Ning Fan, Alexander Drilon, Helena A. Yu, Gregory J. Riely, Natasha Rekhtman, Álvaro Quintanal Villalonga, Snjezana Dogan, Umesh Bhanot, Mithat Gönen, Brian Loomis, Matthew D. Hellmann, Adam J. Schoenfeld, Marc Ladanyi, Charles M. Rudin, Chad M. Vanderbilt
Journal: Journal of Clinical Oncology (2024)

PURPOSE The impact of the intratumoral microbiome on immune checkpoint inhibitor (ICI) efficacy in patients with non–small-cell lung cancer (NSCLC) is unknown. Preclinically, intratumoral Escherichia is associated with a proinflammatory tumor microenvironment and decreased metastases. We sought to determine whether intratumoral Escherichia is associated with outcome to ICI in patients with NSCLC. PATIENTS AND METHODS We examined the intratumoral microbiome in 958 patients with advanced NSCLC treated with ICI by querying unmapped next-generation sequencing reads against a bacterial genome database. Putative environmental contaminants were filtered using no-template controls (n = 2,378). The impact of intratumoral Escherichia detection on overall survival (OS) was assessed using univariable and multivariable analyses. The findings were further validated in an external independent cohort of 772 patients. Escherichia fluorescence in situ hybridization (FISH) and transcriptomic profiling were performed. RESULTS In the discovery cohort, read mapping to intratumoral Escherichia was associated with significantly longer OS (16 v 11 months; hazard ratio, 0.73 [95% CI, 0.59 to 0.92]; P = .0065) in patients treated with single-agent ICI, but not combination chemoimmunotherapy. The association with OS in the single-agent ICI cohort remained statistically significant in multivariable analysis adjusting for prognostic features including PD-L1 expression ( P = .023). Analysis of an external validation cohort confirmed the association with improved OS in univariable and multivariable analyses of patients treated with single-agent ICI, and not in patients treated with chemoimmunotherapy. Escherichia localization within tumor cells was supported by coregistration of FISH staining and serial hematoxylin and eosin sections. Transcriptomic analysis correlated Escherichia-positive samples with expression signatures of immune cell infiltration. CONCLUSION Read mapping to potential intratumoral Escherichia was associated with survival to single-agent ICI in two independent cohorts of patients with NSCLC.
Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial
Authors: Marcin Dzienis, Juan Cundom, Christian Sebastian Fuentes, Anna Spreafico, Melanie Nordlinger, Andrea Viviana Pastor, Erin Alesi, Anterpreet Neki, Andrea S. Fung, Iane Pinto Figueiredo Lima, Peter Oppelt, Geraldo Felicio da Cunha Junior, Barbara Burtness, Fabio Andre Franke, Jennifer E. Tseng, Abhishek Joshi, Joy McCarthy, Ramona Swaby, Yulia Sidi, Burak Gumuscu, Niroshini Naicker, Gilberto de Castro
Journal: Journal of Clinical Oncology (2024)

Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.gov identifier: NCT04489888).
Academic Uphill Battle to Personalize Treatment for Patients With Stage II/III Triple-Negative Breast Cancer
Authors: Marleen Kok, Robbert-Jan Gielen, Sylvia Adams, Jochen K. Lennerz, Priyanka Sharma, Sibylle Loibl, Erin Reardon, Gabe Sonke, Sabine Linn, Suzette Delaloge, Denis Lacombe, Tim Robinson, Sunil Badve, Miguel Martin, Justin M. Balko, Michail Ignatiadis, Giuseppe Curigliano, Antonio C. Wolff, Elizabeth A. Mittendorf, Sherene Loi, Lajos Pusztai, Sara M. Tolaney, Roberto Salgado
Journal: Journal of Clinical Oncology (2024)
Stockholm3 in a Multiethnic Cohort for Prostate Cancer Detection (SEPTA): A Prospective Multicentered Trial
Authors: Hari T. Vigneswaran, Martin Eklund, Andrea Discacciati, Tobias Nordström, Rebecca A. Hubbard, Nathan Perlis, Michael R. Abern, Daniel M. Moreira, Scott Eggener, Paul Yonover, Alexander K. Chow, Kara Watts, Michael A. Liss, Gregory R. Thoreson, Andre L. Abreu, Geoffrey A. Sonn, Thorgerdur Palsdottir, Anna Plym, Fredrik Wiklund, Henrik Grönberg, Adam B. Murphy
Journal: Journal of Clinical Oncology (2024)

PURPOSE Asian, Black, and Hispanic men are underrepresented in prostate cancer (PCa) clinical trials. Few novel prostate cancer biomarkers have been validated in diverse cohorts. We aimed to determine if Stockholm3 can improve prostate cancer detection in a diverse cohort. METHODS An observational prospective multicentered (17 sites) clinical trial (2019-2023), supplemented by prospectively recruited participants (2008-2020) in a urology clinic setting included men with suspicion of PCa and underwent prostate biopsy. Before biopsy, sample was collected for measurement of the Stockholm3 risk score. Parameters include prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, germline risk (single-nucleotide polymorphisms), age, family history, and previous negative biopsy. The primary endpoint was detection of International Society of Urological Pathology (ISUP) Grade ≥2 cancer (clinically significant PCa, csPC). The two primary aims were to (1) demonstrate noninferior sensitivity (0.8 lower bound 95% CI noninferiority margin) in detecting csPC using Stockholm3 compared with PSA (relative sensitivity) and (2) demonstrate superior specificity by reducing biopsies with benign results or low-grade cancers (relative specificity). RESULTS A total of 2,129 biopsied participants were included: Asian (16%, 350), Black or African American (Black; 24%, 505), Hispanic or Latino and White (Hispanic; 14%, 305), and non-Hispanic or non-Latino and White (White; 46%, 969). Overall, Stockholm3 showed noninferior sensitivity compared with PSA ≥4 ng/mL (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) and nearly three times higher specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). Results were consistent across racial and ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Compared with PSA, Stockholm3 could reduce benign and ISUP 1 biopsies by 45% overall and between 42% and 52% across racial and ethnic subgroups. CONCLUSION In a substantially diverse population, Stockholm3 significantly reduces unnecessary prostate biopsies while maintaining a similar sensitivity to PSA in detecting csPC.
Sharing the Burden: The Case for Definitive Local Therapy in Place of Immune Checkpoint Blockade for Patients With a Low-Volume Burden of Metastatic Disease
Authors: Connor Lynch, Muzamil Arshad, Rohan R. Katipally, Sean P. Pitroda, Ralph R. Weichselbaum
Journal: Journal of Clinical Oncology (2024)

Commentary: Sharing the burden of low-volume metastatic cancer between ICB and local treatments,
MERS-CoV exposure and risk factors for MERS-CoV ELISA seropositivity among members of livestock-owning households in southern Jordan: a population based cross-sectional study
Authors: Peter M Holloway, Matthew D Gibson, Tanja T Holloway, Neeltje van Doremalen, Vincent J Munster, Bilal Al-Omari, Michael C Letko, Stephen Nash, Jacqueline M Cardwell, Ehab A Abu-Basha, Wail Hayajneh, Punam Mangtani, Javier Guitian
Journal: The Lancet Microbe (2024)

Although dromedary camels (Camelus dromedarius) are known to be the host reservoir for MERS-CoV, the virus causing Middle East respiratory syndrome (MERS), zoonotic transmission pathways and camel subpopulations posing highest transmission risk are poorly understood. Extensively managed herds, ubiquitous across the Arabian Peninsula, present a major potential source of primary infection. In this study we aimed to address key knowledge gaps regarding MERS epidemiology among high-risk communities associated with such herds, which is essential information for effective control strategies.
[18F]RCCB6 Immuno-Positron Emission Tomography/Computed Tomography for Postoperative Surveillance in Clear Cell Renal Cell Carcinoma: A Pilot Clinical Study
Authors: Qianyun Wu, Yanfei Wu, You Zhang, Yihui Guan, Gang Huang, Junhua Zheng, Jianjun Liu, Fang Xie, Weijun Wei, Wei Zhai
Journal: European Urology (2024)
Autonomous artificial intelligence for diabetic eye disease increases access and health equity in underserved populations
Authors: Jane J. Huang, Roomasa Channa, Risa M. Wolf, Yiwen Dong, Mavis Liang, Jiangxia Wang, Michael D. Abramoff, T. Y. Alvin Liu
Journal: npj Digital Medicine (2024)

Diabetic eye disease (DED) is a leading cause of blindness in the world. Annual DED testing is recommended for adults with diabetes, but adherence to this guideline has historically been low. In 2020, Johns Hopkins Medicine (JHM) began deploying autonomous AI for DED testing. In this study, we aimed to determine whether autonomous AI implementation was associated with increased adherence to annual DED testing, and how this differed across patient populations. JHM primary care sites were categorized as "non-AI" (no autonomous AI deployment) or "AI-switched" (autonomous AI deployment by 2021). We conducted a propensity score weighting analysis to compare change in adherence rates from 2019 to 2021 between non-AI and AI-switched sites. Our study included all adult patients with diabetes (>17,000) managed within JHM and has three major findings. First, AI-switched sites experienced a 7.6 percentage point greater increase in DED testing than non-AI sites from 2019 to 2021 (p < 0.001). Second, the adherence rate for Black/African Americans increased by 12.2 percentage points within AI-switched sites but decreased by 0.6% points within non-AI sites (p < 0.001), suggesting that autonomous AI deployment improved access to retinal evaluation for historically disadvantaged populations. Third, autonomous AI is associated with improved health equity, e.g. the adherence rate gap between Asian Americans and Black/African Americans shrank from 15.6% in 2019 to 3.5% in 2021. In summary, our results from real-world deployment in a large integrated healthcare system suggest that autonomous AI is associated with improvement in overall DED testing adherence, patient access, and health equity.
Demystifying the Contemporary Role of 12-Month Dual Antiplatelet Therapy After Acute Coronary Syndrome
Authors: Marco Valgimigli, Antonio Landi, Dominick J. Angiolillo, Usman Baber, Deepak L. Bhatt, Marc P. Bonaca, Davide Capodanno, David J. Cohen, C. Michael Gibson, Stefan James, Takeshi Kimura, Renato D. Lopes, Shamir R. Mehta, Gilles Montalescot, Dirk Sibbing, P. Gabriel Steg, Gregg W. Stone, Robert F. Storey, Pascal Vranckx, Stephan Windecker, Roxana Mehran
Journal: Circulation (2024)

For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.
Illness Trajectories After Revascularization in Patients With Peripheral Artery Disease: A Unified Approach to Understanding the Risk of Major Amputation and Death
Authors: Qiuju Li, Panagiota Birmpili, Eleanor Atkins, Amundeep S. Johal, Sam Waton, Robin Williams, Jonathan R. Boyle, Denis W. Harkin, Arun D. Pherwani, David A. Cromwell
Journal: Circulation (2024)

The aim of this study was to investigate the illness trajectories of patients with peripheral artery disease (PAD) after revascularization and estimate the independent risks of major amputation and death (from any cause) and their interaction.
Estimating sojourn time and sensitivity of screening for ovarian cancer using a Bayesian framework
Authors: Sayaka Ishizawa, Jiangong Niu, Martin C Tammemagi, Ehsan Irajizad, Yu Shen, Karen H Lu, Larissa A Meyer, Iakovos Toumazis
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Ovarian cancer is among the leading causes of gynecologic cancer-related death. Past ovarian cancer screening trials using combination of cancer antigen 125 testing and transvaginal ultrasound failed to yield statistically significant mortality reduction. Estimates of ovarian cancer sojourn time—that is, the period from when the cancer is first screen detectable until clinical detection—may inform future screening programs. Methods We modeled ovarian cancer progression as a continuous time Markov chain and estimated screening modality–specific sojourn time and sensitivity using a Bayesian approach. Model inputs were derived from the screening arms (multimodal and ultrasound) of the UK Collaborative Trial of Ovarian Cancer Screening and the Prostate, Lung, Colorectal and Ovarian cancer screening trials. We assessed the quality of our estimates by using the posterior predictive P value. We derived histology-specific sojourn times by adjusting the overall sojourn time based on the corresponding histology-specific survival from the Surveillance, Epidemiology, and End Results Program. Results The overall ovarian cancer sojourn time was 2.1 years (posterior predictive P value = .469) in the Prostate, Lung, Colorectal and Ovarian studies, with 65.7% screening sensitivity. The sojourn time was 2.0 years (posterior predictive P value = .532) in the United Kingdom Collaborative Trial of Ovarian Cancer Screening’s multimodal screening arm and 2.4 years (posterior predictive P value = .640) in the ultrasound screening arm, with sensitivities of 93.2% and 64.5%, respectively. Stage-specific screening sensitivities in the Prostate, Lung, Colorectal and Ovarian studies were 39.1% and 82.9% for early-stage and advanced-stage disease, respectively. The histology-specific sojourn times ranged from 0.8 to 1.8 years for type II ovarian cancer and 2.9 to 6.6 years for type I ovarian cancer. Conclusions Annual screening is not effective for all ovarian cancer subtypes. Screening sensitivity for early-stage ovarian cancers is not sufficient for substantial mortality reduction.
Acknowledging and addressing real-world challenges to treating immune-related adverse events
Authors: Mitchell S von Itzstein, David E Gerber, Bonnie L Bermas, Alexa Meara
Journal: Journal for ImmunoTherapy of Cancer (2024)

Immune checkpoint inhibitors (ICIs) have revolutionized oncology treatment. However, their success is mitigated by the recognition that ICI-induced immune-related adverse events (irAEs) pose considerable challenges to patients and clinicians. These autoimmune toxicities are heterogeneous, unpredictable, and reflect a disease state resulting from a change in the immune system of patients. This contrasts with the typical acute nature of toxicities from chemotherapy and molecularly targeted oncology therapies. Management is further complicated by the extended bioavailability of these agents in patients as well as the persistence of autoimmune pathology. Currently, irAE treatment remains suboptimal in many areas, as many expert guidelines remain vague on the optimal selection, dosing, and duration of steroids and the use of other immunosuppressive agents. This coupled with delays in diagnosis and difficulties for patients accessing effective irAE treatment results in barriers to effective irAE care. The latter is complicated by the lack of US Food and Drug Administration-approved irAE treatments that lead to insurance denials, as well as the high cost of biological immunosuppressant therapies. Fortunately, rheumatologists and other subspecialists with expertize in the management of chronic autoimmune conditions have become more involved in irAE diagnosis and management and may help navigate treatment. In this commentary, we discuss these issues and propose potential solutions to advance the field.
Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases
Authors: Chandra C Ghosh, Lauren Cournoyer, Yujia Liu, Alizee Ballarin, Ilan B Layman, Jason LaPorte, Molly Morrissey, Kayla Fraser, Shriya Perati, Bryan F Cox, Evgeny Yakirevich, Diana O Treaba, Timothy D Murtha, Prajna Guha, Steven C Katz, Diwakar Davar
Journal: Journal for ImmunoTherapy of Cancer (2024)

Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious micro-organisms, cancer cells and develop adaptive immune responses. Their ability as immunomodulators to enhance the activity of checkpoint inhibitors (CPI) in treating liver tumors is limited in part by the distinctive biology of intrahepatic myeloid-derived suppressor cells (MDSC) and challenges with tumor-specific therapeutic delivery. We have shown that the regional delivery of type C TLR9 agonist via pressure-enabled drug delivery (PEDD) system improves delivery to the tumor, enhances depletion of MDSCs and overall, stimulates the immune system in combination with or without CPI. Currently, CPIs are delivered intravenously, although there is a growing interest in its subcutaneous (SQ) administration. We compared nelitolimod formerly known as SD-101 administered using PEDD in combination with systemic (Sys) or SQ CPI in murine liver metastases (LM). The LM model was developed by injecting MC38-Luc cells via the spleen of 8-12 week old male C57/BL6 mice followed by splenectomy. After a week, fluorescently labeled nelitolimod (10 µg/mouse) was delivered via PEDD and co-administered anti-programmed cell death-1 (α-PD-1) either via Sys or SQ. Tumor burden was monitored by in vivo imaging system. Serum cytokine levels were analyzed by Luminex. Tissues were harvested on Day 3 (D3) or Day 10 (D10) post-PEDD to enrich CD45+ cells and were analyzed via NanoString targeted transcriptomics (D3) or flow cytometry (FC, D10) to interrogate immune cell populations (D10). For NanoString analysis, the innate immune panels were selected, and for FC, MDSCs (CD11b+Gr1+), B cells (B220+), dendritic cells (DC, CD11c+), T (CD3+) cells, and M1-like macrophages (F4/80+CD38+Egr2-) were quantified. Nelitolimod delivered via PEDD resulted in changes in innate and adaptive immune cells within LM, including depletion of liver MDSC and increased M1-like macrophages in the liver, which are supportive of antitumor immunity. While CPI monotherapy failed to control tumor progression, nelitolimod and CPI combination improved LM control, survival and antitumor immunity beyond the nelitolimod monotherapy effect, irrespective of CPI delivery route. The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment.
Human DNA Extraction and Sequencing From Cardiomyocytes Collected by Catheter-Based Aspiration
Authors: Philippe Maury, Flavie Ader, Emeline Lhuillier, Frédéric Martins, Maxime Beneyto, Céline Gales, Eric Villard, Laetitia Duboscq-Bidot, Estelle Gandjbakhch, Céline Guilbeau-Frugier
Journal: Journal of the American College of Cardiology (2024)
A Shot Through the Heart
Authors: J.W. Taco Boltje, Siem J. de Haan, David E. Vecht, H. Reinier Zandbergen, Ramon B. van Loon, Frank W. Bloemers, Meike P. Haverkamp, Patrick Klein
Journal: Journal of the American College of Cardiology (2024)

We present the case of a patient who was shot through the heart with an air rifle and presented in a stable condition at our emergency department. At the time of presentation, the bullet was still present within the myocardium. Imaging, management, and outcome are discussed in this report.
Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer
Authors: Niels E Wondergem, Iris H C Miedema, Rieneke van de Ven, Gerben J C Zwezerijnen, Pim de Graaf, K Hakki Karagozoglu, Jan-Jaap Hendrickx, Simone E J Eerenstein, Rolf J Bun, Dorien C Mulder, Jens Voortman, Ronald Boellaard, Albert D Windhorst, J Pascal Hagers, Laura A N Peferoen, Tanja D de Gruijl, Elisabeth Bloemena, Ruud H Brakenhoff, C René Leemans, C Willemien Menke-van der Houven van Oordt
Journal: Journal for ImmunoTherapy of Cancer (2024)

Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome.