tbuckley/cabot-search huggingface dataset:
The Precise Relationship Between Model for End‐Stage Liver Disease and Survival Without a Liver Transplant
Authors: Douglas N. VanDerwerken, Nicholas L. Wood, Dorry L. Segev, Sommer E. Gentry
Journal: Hepatology (2021)

Scores from the Model for End-Stage Liver Disease (MELD), which are used to prioritize candidates for deceased donor livers, are widely acknowledged to be negatively correlated with the 90-day survival rate without a liver transplant. However, inconsistent and outdated estimates of survival probabilities by MELD preclude useful applications of the MELD score.Using data from all prevalent liver waitlist candidates from 2016 to 2019, we estimated 3-day, 7-day, 14-day, 30-day, and 90-day without-transplant survival probabilities (with confidence intervals) for each MELD score and status 1A. We used an adjusted Kaplan-Meier model to avoid unrealistic assumptions and multiple observations per person instead of just the observation at listing. We found that 90-day without-transplant survival has improved over the last decade, with survival rates increasing >10% (in absolute terms) for some MELD scores. We demonstrated that MELD correctly prioritizes candidates in terms of without-transplant survival probability but that status 1A candidates' short-term without-transplant survival is higher than that of MELD 40 candidates and lower than that of MELD 39 candidates. Our primary result is the updated survival functions themselves.We calculated without-transplant survival probabilities for each MELD score (and status 1A). The survival function is an invaluable tool for many applications in liver transplantation: awarding of exception points, calculating the relative demand for deceased donor livers in different geographic areas, calibrating the pediatric end-stage liver disease score, and deciding whether to accept an offered liver.
Screening for Lung Cancer
Authors: Alex H. Krist, Karina W. Davidson, Carol M. Mangione, Michael J. Barry, Michael Cabana, Aaron B. Caughey, Esa M. Davis, Katrina E. Donahue, Chyke A. Doubeni, Martha Kubik, C. Seth Landefeld, Li Li, Gbenga Ogedegbe, Douglas K. Owens, Lori Pbert, Michael Silverstein, James Stevermer, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2021)

<h3>Importance</h3> Lung cancer is the second most common cancer and the leading cause of cancer death in the US. In 2020, an estimated 228 820 persons were diagnosed with lung cancer, and 135 720 persons died of the disease. The most important risk factor for lung cancer is smoking. Increasing age is also a risk factor for lung cancer. Lung cancer has a generally poor prognosis, with an overall 5-year survival rate of 20.5%. However, early-stage lung cancer has a better prognosis and is more amenable to treatment. <h3>Objective</h3> To update its 2013 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the accuracy of screening for lung cancer with low-dose computed tomography (LDCT) and on the benefits and harms of screening for lung cancer and commissioned a collaborative modeling study to provide information about the optimum age at which to begin and end screening, the optimal screening interval, and the relative benefits and harms of different screening strategies compared with modified versions of multivariate risk prediction models. <h3>Population</h3> This recommendation statement applies to adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. <h3>Evidence Assessment</h3> The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT has a moderate net benefit in persons at high risk of lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. <h3>Recommendation</h3> The USPSTF recommends annual screening for lung cancer with LDCT in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) This recommendation replaces the 2013 USPSTF statement that recommended annual screening for lung cancer with LDCT in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years.
Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19
Authors: Peter A. Szabo, Pranay Dogra, Joshua I. Gray, Steven B. Wells, Thomas J. Connors, Stuart P. Weisberg, Izabela Krupska, Rei Matsumoto, Maya M.L. Poon, Emma Idzikowski, Sinead E. Morris, Chloé Pasin, Andrew J. Yates, Amy Ku, Michael Chait, Julia Davis-Porada, Xinzheng V. Guo, Jing Zhou, Matthew Steinle, Sean Mackay, Anjali Saqi, Matthew R. Baldwin, Peter A. Sims, Donna L. Farber
Journal: Immunity (2021)
Venetoclax sensitivity in multiple myeloma is associated with B-cell gene expression
Authors: Vikas A. Gupta, Benjamin G. Barwick, Shannon M. Matulis, Ryosuke Shirasaki, David L. Jaye, Jonathan J. Keats, Benjamin Oberlton, Nisha S. Joseph, Craig C. Hofmeister, Leonard T. Heffner, Madhav V. Dhodapkar, Ajay K. Nooka, Sagar Lonial, Constantine S. Mitsiades, Jonathan L. Kaufman, Lawrence H. Boise
Journal: Blood (2021)
The positive impact of implementing an onsite guideline-based genetic testing procedure for prostate cancer in a multidisciplinary uro-oncology clinic.
Authors: Siddharth Ramanathan, Sadhna Ramanathan, Andrew Korman, Samer Ballouz, Michael Ghilezan, Michael Levin, Kirk Wojno, Alvaro Martinez, Howard Korman, Savitha Balaraman
Journal: Journal of Clinical Oncology (2021)

234 Background: Prior to the guidelines set forth by the 2017 Philadelphia consensus conference, genetic testing for prostate cancer was conducted based on personal and family history of malignancies pursuant to NCCN recommendations. The 2017 guidelines expanded testing criteria to included age at diagnosis, metastatic disease, and tumor sequencing. In spite of these advancements, limited literature is available regarding successful implementation of a streamlined system for genetic testing in prostate cancer. This paper explores the benefits of implementing an on-site guideline-based genetic testing process for prostate cancer patients treated at a multi-disciplinary uro-oncology practice. Methods: Data was retrospectively reviewed for 561 prostate cancer patients seen in a multi-disciplinary uro-oncology clinic since January 2017. Prior to January, 1, 2019 genetic testing was recommended to patients based on NCCN guidelines, and swabs for testing were procured off-site less than 1 mile from the clinic (n=107). After January, 1, 2019 genetic testing was recommended based on the guidelines set forth by the Philadelphia consensus conference, and swabs for testing were procured at the clinic itself (n=454). Results: A statistically significant increase in compliance with genetic testing was observed after the implementation of an on-site, guideline-based testing process. Patient compliance with genetic testing increased from 33.6% to 96.5%. The time to receive the genetic test results (calculated as the time between referral for genetic testing and obtaining the test results) was also significantly improved from 38 days to 21 days. Conclusions: The implementation of an on-site, guideline-based genetic testing model for prostate cancer patients significantly improved compliance with genetic testing to 96.5% and decreased the time to receive genetic test results by 17 days. Overall, adopting a guide-line based model with on-site genetic testing has the potential to significantly improve the detection rate for pathogenic and actionable mutations, increase the utilization of targeted therapies, and increase cascade testing to include at-risk family members.
Abstract PO-093: Evaluating dependencies by rapid image-based <i>ex vivo</i> cancer biosensors
Authors: Mushriq Al-Jazrawe, Csaba Molnar, Niklas Rindtorff, Pinar Eser, Sean Misek, Maria Alimova, Oana Ursu, William Colgan, Adel Attari, Natalie Tsang, Paula Keskula, Carmen Rios, Moony Tseng, Anne Carpenter, James McFarland, Adam Bass, Samuel Klempner, Jesse Boehm
Journal: Clinical Cancer Research (2021)

Abstract Successful mapping of cancer dependencies requires conducting genetic and drug screens on a diversity of models. However, the difficulty in generating long-term models of many cancers limits the share of patient samples that can be studied. Such long-term models have likely also lost the cellular heterogeneity present in the original tumor due to in vitro propagation. To overcome these limitations, we are developing image-based ex vivo cancer biosensors from early patient material. Using freshly received gastroesophageal cancer ascites, we are optimizing perturbation methods and utilizing single-cell transcriptomics and label-free microscopy to infer a subpopulation-specific vulnerability profile. We show that label-free microscopy can infer cell identity and viability in heterogeneous early patient samples. Additionally, early drug perturbation recapitulates observations made in established gastroesophageal cancer organoids. Successful implementation of ex vivo biosensors will expand the cancer dependency space by making perturbational studies accessible to more diverse samples, and by identifying and validating hits in a more immediate setting to the original tumor. Citation Format: Mushriq Al-Jazrawe, Csaba Molnar, Niklas Rindtorff, Pinar Eser, Sean Misek, Maria Alimova, Oana Ursu, William Colgan, Adel Attari, Natalie Tsang, Paula Keskula, Carmen Rios, Moony Tseng, Anne Carpenter, James McFarland, Adam Bass, Samuel Klempner, Jesse Boehm. Evaluating dependencies by rapid image-based ex vivo cancer biosensors [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-093.
A phase I/II study of hydroxychloroquine and suba-itraconazole in men with biochemical relapse of prostate cancer (HITMAN-PC): Dose escalation results.
Authors: Brandon Lau, Megan Crumbaker, Andrew On Wah Yam, Stefano Marastoni, Mathew Luckhurst, Aaron O'Grady, Brad Wouters, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2021)

114 Background: Preclinical data show hydroxychloroquine (HCQ) and suba-itraconazole (SI) together enhance prostate cancer cell death. The proposed mechanism is lysosome dysfunction including sequestration of cholesterol in endosomes and inhibition of gogi-lyosome trafficking. HCQ/SI could delay androgen deprivation therapy (ADT) and its associated morbidity in men with biochemical relapse of prostate cancer. In this phase I/II study, maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of HCQ/SI was investigated in such patients. Methods: Patients received escalating doses of HCQ with fixed SI 150mg BD in rolling 6 design. This will be followed by a planned phase II Simon 2-stage cohort expansion. Results: Eleven men were treated with HCQ/SI. Median age 73 (range 69-77), baseline PSA 4.4 µg/L (1.6-22.4) and doubling time 5.3 months (3.3-15.3). Two experienced dose-limiting toxicity: grade 3 diarrhoea and grade 3 alanine transferase elevation, both at HCQ 600mg BD. Most common treatment-related adverse events (AEs) were hypertension (91% all grade/18% grade 3), QTc prolongation (55%/0%), diarrhoea (36%/9%), and nausea (36%/0%). There were no grade 4 AEs or deaths. While there were no PSA responses (≥50% fall from baseline), PSA PFS by PCWG3 criteria was 5.5 months (2.0-9.0), and PSA doubling time was prolonged at 4 and 12 weeks in 82% and 45% respectively. ADT-free and metastasis-free survival are 14.3 months (95% CI 4.9-23.8) and 15.9 months (95% CI unevaluable) respectively. PK data will be presented. Conclusions: HCQ/SI demonstrated acceptable safety with MTD 600mg BD and RP2D 400mg BD. There is early signal of activity and phase II enrolment is to begin. Clinical trial information: NCT03513211.
INTACT (S/N1806) phase III randomized trial of concurrent chemoradiotherapy with or without atezolizumab in localized muscle-invasive bladder cancer: Safety update on first 73 patients.
Authors: Parminder Singh, Jason A. Efstathiou, Catherine Tangen, Sameer G. Jhavar, Noah M. Hahn, Brian Addis Costello, Scott Edward Delacroix, Abhishek Tripathi, Sean Sachdev, Jessie Gills, Ashesh B. Jani, Rick Bangs, Melissa Plets, Nicholas J. Vogelzang, Ian Murchie Thompson, Felix Y Feng, Seth P. Lerner
Journal: Journal of Clinical Oncology (2021)

428 Background: Trimodality therapy (TMT) with maximal TURBT followed by chemoradiation(CRT) is a standard of care for select patients with muscle invasive bladder cancer (MIBC). This trial evaluates the activity of atezolizumab (atezo) in MIBC in combination with TMT. This trial was designed with pre-specified safety analyses of the first 80 patients (40 in each arm). At the time of SWOG fall 2020 DSMC report deadline we had enrolled 84 patients but data on only 73 patients were available. The same data are being submitted to ASCO GU meeting. Methods: This trial is testing atezo every 3 weeks for 6 months given concurrently and adjuvantly with CRT vs. CRT alone in 475 patients with MIBC T2-T4aN0M0 disease. Patients are stratified based on PS; T2 vs T3 or T4; choice of chemotherapy; and radiation field (bladder only vs small pelvis). Patients undergo biopsy 3 months after finishing CRT to assess treatment response. Patients are followed for 5 years for recurrence or survival. This trial was not preceded by a phase I study but was designed with a safety run in of 80 patients. Study team agreed on the study design based on available data from other tumor types and initial experience from investigators running smaller similar trials. It was pre-specified that if we observe more than 25% patients having grade 3-5 colitis or cystitis in the atezo arm or any other toxicity which is deemed clinically significant and related to atezo, the trial investigators and DSMC would consider stopping further enrollment. Results: 36 patients were enrolled on the TMT alone arm and 37 patients on the TMT + atezo arm. No grade 3 or higher colitis was reported in the atezo arm. Only one patient had treatment related grade 3 radiation cystitis which was diagnosed after finishing atezo treatment. No steroids were given. Overall 23 grade 3 or higher toxicity events were reported in the atezo arm vs 11 in non- atezo arm. Most common toxicity was hematological which was considered non-immune related. None of the grade 3 or higher toxicities were considered to be immune related by the treating investigator. Conclusions: There is no evidence of increased immune related grade 3-5 AEs.DSMC has recommended to continue enrollment. Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed Clinical trial information: NCT03775265 . [Table: see text]
Evaluation of Stigma Toward Individuals With Alopecia
Authors: Andrew Creadore, Priya Manjaly, Sara J. Li, Elizabeth Tkachenko, Guohai Zhou, Cara Joyce, Kathie P. Huang, Arash Mostaghimi
Journal: JAMA Dermatology (2021)

Perceived stigma among patients with alopecia is associated with impaired quality of life; however, the magnitude of laypersons' stigma toward individuals with alopecia is unknown.To determine the prevalence and magnitude of laypersons' stigma toward individuals with varying degrees of alopecia and whether stigma increases with increased severity of alopecia.This was a cross-sectional study using an internet survey administered to a convenience sample of adult respondents in the US participating on the Amazon Mechanical Turk platform. Portrait images of 6 individuals without hair loss were created using artificial intelligence and stock images. Each portrait was edited to create 2 additional versions, 1 with scalp hair loss and 1 with complete hair loss, for a total of 18 images. On January 9 to 10, 2020, the survey presented each internet respondent with 1 randomly selected portrait to be used in answering a series of stigma-related questions from 3 domains: stereotypes, social distance, and disease-related myths; the third domain was presented only to respondents who believed that the individual pictured had a medical condition.The main outcome was the prevalence and magnitude of stigma of laypersons toward individuals with alopecia and the percentage of laypersons who believed the individual pictured had a medical condition as recorded in survey responses.The survey was completed by 2015 respondents (99.9% completion rate) with a mean age of 37 (range, 18-78) years; 1014 (50.3%) were men; 1596 (79.2%) were White; and 1397 (69.3%) had a college or postcollege education. Endorsement of every stigma item increased as alopecia severity increased (2.4%-27.6%). Absolute change on the stereotype (0.5-0.6) and social distance scales (0.2-0.5) also increased, indicating more stigma. The percentage of respondents believing the individual pictured had a medical condition increased as alopecia severity increased (33.6%-75.7%; P < .001). Among the subgroup of respondents who were asked to rate their agreement with disease-related myths, the absolute change on the myth scale decreased as alopecia severity increased, indicating decreased stigma (-0.7 to -1.2).This cross-sectional survey study found that stigmatizing attitudes of laypersons toward patients with alopecia exist across a multitude of social and professional scenarios. Stigma prevalence and magnitude vary by alopecia severity and possibly by whether alopecia is believed to be a medical condition.
Human papillomavirus vaccination for adults aged 30 to 45 years in the United States: A cost-effectiveness analysis
Authors: Jane J. Kim, Kate T. Simms, James Killen, Megan A. Smith, Emily A. Burger, Stephen Sy, Catherine Regan, Karen Canfell
Journal: PLoS Medicine (2021)

Background A nonavalent human papillomavirus (HPV) vaccine has been licensed for use in women and men up to age 45 years in the United States. The cost-effectiveness of HPV vaccination for women and men aged 30 to 45 years in the context of cervical cancer screening practice was evaluated to inform national guidelines. Methods and findings We utilized 2 independent HPV microsimulation models to evaluate the cost-effectiveness of extending the upper age limit of HPV vaccination in women (from age 26 years) and men (from age 21 years) up to age 30, 35, 40, or 45 years. The models were empirically calibrated to reflect the burden of HPV and related cancers in the US population and used standardized inputs regarding historical and future vaccination uptake, vaccine efficacy, cervical cancer screening, and costs. Disease outcomes included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. Both models projected higher costs and greater health benefits as the upper age limit of HPV vaccination increased. Strategies of vaccinating females and males up to ages 30, 35, and 40 years were found to be less cost-effective than vaccinating up to age 45 years, which had an incremental cost-effectiveness ratio (ICER) greater than a commonly accepted upper threshold of $200,000 per quality-adjusted life year (QALY) gained. When including all HPV-related outcomes, the ICER for vaccinating up to age 45 years ranged from $315,700 to $440,600 per QALY gained. Assumptions regarding cervical screening compliance, vaccine costs, and the natural history of noncervical HPV-related cancers had major impacts on the cost-effectiveness of the vaccination strategies. Key limitations of the study were related to uncertainties in the data used to inform the models, including the timing of vaccine impact on noncervical cancers and vaccine efficacy at older ages. Conclusions Our results from 2 independent models suggest that HPV vaccination for adult women and men aged 30 to 45 years is unlikely to represent good value for money in the US.
Tilsotolimod with Ipilimumab Drives Tumor Responses in Anti–PD-1 Refractory Melanoma
Authors: Cara Haymaker, Daniel H. Johnson, Ravi Murthy, Salah-Eddine Bentebibel, Marc I. Uemura, Courtney W. Hudgens, Houssein Safa, Marihella James, Robert H.I. Andtbacka, Douglas B. Johnson, Montaser Shaheen, Michael A. Davies, Shah Rahimian, Srinivas K. Chunduru, Denái R. Milton, Michael T. Tetzlaff, Willem W. Overwijk, Patrick Hwu, Nashat Gabrail, Sudhir Agrawal, Gary Doolittle, Igor Puzanov, Joseph Markowitz, Chantale Bernatchez, Adi Diab
Journal: Cancer Discovery (2021)

Abstract Many patients with advanced melanoma are resistant to immune checkpoint inhibition. In the ILLUMINATE-204 phase I/II trial, we assessed intratumoral tilsotolimod, an investigational Toll-like receptor 9 agonist, with systemic ipilimumab in patients with anti–PD-1– resistant advanced melanoma. In all patients, 48.4% experienced grade 3/4 treatment-emergent adverse events. The overall response rate at the recommended phase II dose of 8 mg was 22.4%, and an additional 49% of patients had stable disease. Responses in noninjected lesions and in patients expected to be resistant to ipilimumab monotherapy were observed. Rapid induction of a local IFNα gene signature, dendritic cell maturation and enhanced markers of antigen presentation, and T-cell clonal expansion correlated with clinical response. A phase III clinical trial with this combination (NCT03445533) is ongoing. Significance: Despite recent developments in advanced melanoma therapies, most patients do not experience durable responses. Intratumoral tilsotolimod injection elicits a rapid, local type 1 IFN response and, in combination with ipilimumab, activates T cells to promote clinical activity, including in distant lesions and patients not expected to respond to ipilimumab alone. This article is highlighted in the In This Issue feature, p. 1861
Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma
Authors: Toni K. Choueiri, Thomas Powles, Mauricio Burotto, Bernard Escudier, Maria T. Bourlon, Bogdan Zurawski, Victor M. Oyervides Juárez, James J. Hsieh, Umberto Basso, Amishi Y. Shah, Cristina Suárez, Alketa Hamzaj, Jeffrey C. Goh, Carlos Barrios, Martin Richardet, Camillo Porta, Rubén Kowalyszyn, Juan P. Feregrino, Jakub Żołnierek, David Pook, Elizabeth R. Kessler, Yoshihiko Tomita, Ryuichi Mizuno, Jens Bedke, Joshua Zhang, Matthew A. Maurer, Burcin Simsek, Flavia Ejzykowicz, Gisela M. Schwab, Andrea B. Apolo, Robert J. Motzer
Journal: New England Journal of Medicine (2021)

The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known.
Abstract 2652: Another Normal Variant With ST Elevation and Inverted T Wave Mimicking ST-elevation Myocardial Infarction: The Prevalence, Age and Gender Distribution
Authors: Kyuhvun Wang, Henri Roukoz
Journal: Circulation (2009)

Background: Early repolarization pattern (ERP) is a well known normal variant. There is another kind of ST elevation in the mid precordial leads as a normal variant (Fig 1), which is distinctively ...
Medicare’s New Device-Coverage Pathway — Breakthrough or Breakdown?
Authors: Vinay K. Rathi, James L. Johnston, Joseph S. Ross, Sanket S. Dhruva
Journal: New England Journal of Medicine (2021)

CMS recently finalized a rule that could substantially alter Medicare-coverage decisions for certain new medical devices. The rule is intended to expedite coverage, but it would undermine Medicare's authority to consider the clinical evidence supporting device adoption.