tbuckley/cabot-search huggingface dataset:
A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: the AVATAR Trial
Authors: Francesca Sarno, Jair Tenorio, Sofia Perea, Laura Medina, Roberto Pazo-Cid, Ignacio Juez, Rocío Garcia-Carbonero, Jaime Feliu, Carmen Guillen-Ponce, Pedro P. Lopez-Casas, Carmen Guerra, Yolanda Duran, José Francisco López-Acosta, Carolina Alonso, Estrella Esquivel, Ana Dopazo, Dipikaa Akshinthala, Senthil K. Muthuswamy, Pablo Lapunzina, Bruno Bockorny, Manuel Hidalgo
Journal: Clinical Cancer Research (2024)

Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options. We compared the efficacy of comprehensive precision medicine against that of the conventional treatment in PDAC. We report a phase III trial of advanced PDAC in which patients were randomized (1:2) to a conventional treatment treated at physician's discretion (arm A) or to precision medicine (arm B). Subjects randomized to arm B underwent a tumor biopsy for whole-exome sequencing and to generate avatar mouse models and patient-derived organoids for phenotypic drug screening, with final treatment recommended by the molecular tumor board. The primary objective was median overall survival (OS). A total of 137 patients were enrolled with 125 randomized, 44 to arm A and 81 to arm B. Whole-exome sequencing was performed in 80.3% (65/81) patients of arm B, with potentially actionable mutations detected in 21.5% (14/65). Experimental models were generated in 16/81 patients (19.8%). Second-line treatment was administered to 39 patients in the experimental arm, but only four (10.2%) received personalized treatment, whereas 35 could not receive matched therapy because of rapid clinical deterioration, delays in obtaining study results, or the absence of actionable targets. The median OS was 8.7 and 8.6 months (P = 0.849) and the median progression-free survival was 3.8 and 4.3 months (P = 0.563) for the conventional and experimental arms, respectively. Notably, the four patients who received personalized treatment had a median OS of 19.3 months. Personalized medicine was challenging to implement in most patients with PDAC, limiting the interpretation of intention-to-treat analysis. Survival was improved in the subset of patients who did receive matched therapy.
CD40 agonist on patient-derived xenograft mice for the treatment of B-cell acute lymphoblastic leukemia
Authors: Pierre-Simon Bellaye, Aleksandra Georgievski, Paola Ballerini, Boutheina Bouslama, Corentin Richard, Romain Boidot, Guillaume Chevreux, Véronique Legros, Julien Guy, Jessica Racine, Bertrand Collin, Carmen Garrido, Ronan Quéré
Journal: Clinical Cancer Research (2024)

Cluster of differentiation 40 (CD40) is expressed on B-cell acute lymphoblastic leukemia (B-ALL) cases. However, the effect of CD40 activation on B-ALL cells has never been tested in vivo.
Inebilizumab for Treatment of IgG4-Related Disease
Authors: John H. Stone, Arezou Khosroshahi, Wen Zhang, Emanuel Della Torre, Kazuichi Okazaki, Yoshiya Tanaka, J. Matthias Löhr, Nicolas Schleinitz, Lingli Dong, Hisanori Umehara, Marco Lanzillotta, Zachary S. Wallace, Mikael Ebbo, George J. Webster, Fernando Martinez Valle, Manu K. Nayar, Cory A. Perugino, Vinciane Rebours, Xinxin Dong, Yanping Wu, Qing Li, Nishi Rampal, Daniel Cimbora, Emma L. Culver
Journal: New England Journal of Medicine (2024)

IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease. In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization in a 1:1 ratio to receive inebilizumab (300-mg intravenous infusions on days 1 and 15 and week 26) or placebo for a 52-week treatment period. Participants in both groups received identical glucocorticoid tapers. Glucocorticoids were allowed to treat disease flares, but background immunosuppressants were not permitted. The primary end point was the first treated, adjudicated disease flare during the treatment period, assessed in a time-to-event analysis. Key secondary end points were the annualized flare rate and treatment-free and glucocorticoid-free complete remission. A total of 135 participants with IgG4-related disease underwent randomization: 68 participants were assigned to receive inebilizumab and 67 were assigned to receive placebo. Treatment with inebilizumab reduced flare risk; 7 participants (10%) in the inebilizumab group had at least one flare, as compared with 40 participants (60%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.06 to 0.28; P<0.001). The annualized flare rate was lower with inebilizumab than with placebo (rate ratio, 0.14; 95% CI, 0.06 to 0.31; P<0.001). More participants in the inebilizumab group than in the placebo group had flare-free, treatment-free complete remission (odds ratio, 4.68; 95% CI, 2.21 to 9.91; P<0.001) and flare-free, glucocorticoid-free complete remission (odds ratio, 4.96; 95% CI, 2.34 to 10.52; P<0.001). Serious adverse events occurred during the treatment period in 12 of the participants (18%) who received inebilizumab and 6 of the participants (9%) who received placebo. Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease. (Funded by Amgen; MITIGATE ClinicalTrials.gov number, NCT04540497.).
COVID-19 Incidence and Age Eligibility for Elementary School
Authors: Eve Lin, Alyssa Bilinski, Philip A. Collender, Vivian Lee, Sohil R. Sud, Tomás M. León, Lauren A. White, Justin V. Remais, Jennifer R. Head
Journal: JAMA Network Open (2024)

Importance Understanding the role of school attendance on transmission of SARS-CoV-2 among children is of importance for responding to future epidemics. Estimating discontinuities in outcomes by age of eligibility for school attendance has been used to examine associations between school attendance and a variety of outcomes, but has yet to be applied to describe associations between school attendance and communicable disease transmission. Objective To estimate the association between eligibility for elementary school and COVID-19 incidence. Design, Setting, and Participants This case series used data on all pediatric COVID-19 cases reported to California’s disease surveillance system between May 16, 2020, and December 15, 2022, among children within 24 months of the age threshold for school eligibility. Exposure Birthdate before or after the age threshold for elementary school eligibility during periods when school was remote vs in person. Main Outcomes and Measures COVID-19 cases and hospitalizations. Results Between May 16, 2020, and December 15, 2022, there were 688 278 cases of COVID-19 (348 957 cases [50.7%] among boys) and 1423 hospitalizations among children who turned 5 years within 24 months of September 1 of the school year when their infection occurred. The mean (SD) age of the study sample was 5.0 (1.3) years. After adjusting for higher rates of testing in schooled populations, the estimated pooled incidence rate ratio among kindergarten-eligible individuals (eg, those born just before the age threshold for school eligibility) compared with those born just after the eligibility threshold for in-person fall 2021 semester was 1.52 (95% CI, 1.36-1.68), for in-person spring 2022 semester was 1.26 (95% CI, 1.15-1.39), and for in-person fall 2022 semester was 1.19 (95% CI, 1.03-1.38). Reported incidence rates among school-eligible children remained higher during the month-long winter 2021-2022 school break but were lower during the longer summer break that followed. The findings were unable to establish whether associations between school eligibility and COVID-19 incidence were based on in-school vs out-of-school routes (eg, classrooms vs school buses). The study lacked power to detect associations between school attendance and hospitalization. Results were robust to functional form. A simulation study was conducted to demonstrate bias associated with nonadjustment for differential case acquisition by exposure status. Conclusions and Relevance In this case series of children in California, the magnitude of the association between school eligibility and COVID-19 incidence decreased over time and was generally lower than other published associations between out-of-school child social interactions and COVID-19 incidence. This regression discontinuity design approach could be adapted to other geographies and/or disease systems to assess associations between schooling and disease transmission.
Trends in Hospitalizations and Liver Transplants Associated With Alcohol-Induced Liver Disease
Authors: Vrishketan Sethi, Ramon Bataller, Hao Liu, Kristine M. Ruppert, Michele Molinari
Journal: JAMA (2024)

This study investigates trends in hospitalization and liver transplant rates in the US from 2005 to 2021 associated with alcohol-induced liver disease.
Spinal Cord Stimulation vs Medical Management for Chronic Back and Leg Pain
Authors: Frank J. P. M. Huygen, Konstantinos Soulanis, Ketevan Rtveladze, Sheily Kamra, Max Schlueter
Journal: JAMA Network Open (2024)

Chronic back and lower extremity pain is one of the leading causes of disability worldwide. Spinal cord stimulation (SCS) aims to improve symptoms and quality of life.
Rhabdomyolysis and Sodium-Glucose–Linked Transport Inhibitors in Patients Taking Statins
Authors: Ziv Harel, Nivethika Jeyakumar, Graham Smith, Joel G. Ray, Kristin K. Clemens, David N. Juurlink
Journal: JAMA Network Open (2024)

This case-control study investigates the risk of rhabdomyolysis among patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors.
Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy
Authors: Samuel J. Tingle, Nicholas D. H. Chung, Abdullah K. Malik, Georgios Kourounis, Emily Thompson, Emily K. Glover, Jennifer Mehew, Jennifer Philip, Dale Gardiner, Gavin J. Pettigrew, Chris Callaghan, Neil S. Sheerin, Colin H. Wilson
Journal: JAMA Network Open (2024)

Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time.
Quality of Publicly Available Information About Urinary Tract Infections
Authors: Viktoria Schmitz, Zoe Troubh, Michael Durkin, Kevin Hsueh, Katheryn Ney, Brian D. Carpenter, Shinbee Waldron, Mary C. Politi
Journal: JAMA Network Open (2024)

This cross-sectional study examines the content and quality of information about urinary tract infections and asymptomatic bacteriuria on publicly available websites.
Use of Tetracyclines During the Different Stages of Pregnancy
Authors: John N. van den Anker
Journal: JAMA Network Open (2024)

Aya Olivia Nakitanda, MD, PhD; Ingvild Odsbu, MScPharm, PhD; Carolyn E. Cesta, MSc, PhD; Laura Pazzagli, MSc, PhD; Björn Pasternak, MD, PhD
Timing of Neonatal Discharge and Unplanned Readmission to PICUs Among Infants Born Preterm
Authors: Tim J. van Hasselt, Yuhe Wang, Chris Gale, Shalini Ojha, Cheryl Battersby, Peter Davis, Hari Krishnan Kanthimathinathan, Elizabeth S. Draper, Sarah E. Seaton
Journal: JAMA Network Open (2024)

Importance Children born very preterm (&amp;amp;lt;32 weeks) are at risk of ongoing morbidity and admission to pediatric intensive care units (PICUs) in childhood. However, the influence of the timing of neonatal discharge on unplanned PICU admission has not been established. Objective To examine whether the timing of neonatal discharge (postmenstrual age and season) is associated with subsequent unplanned PICU admission. Design, Setting, and Participants This retrospective cohort study used linked national data from the National Neonatal Research Database and Paediatric Intensive Care Audit Network (PICANet) for children born from January 2013 to December 2018 at 22 to 31 weeks’ gestational age who were admitted to a neonatal unit in England and Wales and were discharged home at 34 weeks’ postmenstrual age or later. All National Health Service (NHS) neonatal units and PICUs in England and Wales were included. Children were followed up until 2 years of chronological age. Data analysis was conducted from October 2023 to August 2024. Exposures Timing of discharge. Main Outcomes and Measures The primary outcome was unplanned PICU admission between neonatal discharge and chronological age 2 years to any PICU within England and Wales. Survival analysis using a flexible parametric model was conducted with season of discharge (time-dependent factor), gestation, sex, birth weight less than the 10th centile, bronchopulmonary dysplasia, necrotizing enterocolitis, brain injury, and earlier neonatal discharge (lower quartile of postmenstrual age at discharge for gestation) as variables. Results Of 39 938 children discharged home (median [IQR] gestational age, 29 [27-31] weeks; 21 602 [54.1%] male), 1878 (4.7%) had unplanned PICU admission. More than half of admissions occurred within 50 days of neonatal discharge (1080 [57.5%]). Compared with summer, the risk of unplanned PICU admission following neonatal discharge was 2.58 times higher in winter and 2.35 times higher in autumn (winter: adjusted hazard ratio [aHR], 2.58; 95% CI, 1.68-3.95; autumn: aHR, 2.35; 95% CI, 1.84-2.99). Among children born at 28 to 31 weeks’ gestational age, earlier neonatal discharge was associated with increased risk (aHR, 1.30; 95% CI, 1.13-1.49), but this was not true for children born younger than 28 weeks’ gestational age. Conclusions and Relevance In this retrospective cohort study of preterm children, autumn and winter discharge were associated with the highest risk of unplanned PICU admission following neonatal discharge. For children born at 28 to 31 weeks’ gestational age, discharge at lower postmenstrual age was also associated with increased risk. Further work is required to understand whether delaying neonatal discharge for some children born at 28 to 31 weeks’ gestational age is beneficial and to consider the wider costs and implications of prolonging neonatal care.
Midpregnancy Placental Growth Factor Screening and Early Preterm Birth
Authors: Rachel A. Gladstone, Sumaiya Ahmed, Ella Huszti, Kelsey McLaughlin, John W. Snelgrove, Jennifer Taher, Sebastian R. Hobson, Rory C. Windrim, Kellie E. Murphy, John C. Kingdom
Journal: JAMA Network Open (2024)

Early preterm birth (ie, at less than 34 weeks' gestation) confers a high risk for adverse health outcomes, yet no universal screening strategy exists, preventing targeted delivery of effective interventions.
Race, Gender, and Faculty Retention in Academic Medicine
Authors: Taneisha S. Scheuermann, Lauren Clark, Nasrin Sultana, Nathalia Machado, Elena Shergina, Deepika Polineni, Grace H. Shih, Robert D. Simari, Jo A. Wick, Kimber P. Richter
Journal: JAMA Network Open (2024)

Importance Poor retention may be associated with lack of faculty diversity in academic medicine. Objective To examine differences in faculty retention by gender, degree type, and race and ethnicity using data from US medical schools. Design, Setting, and Participants This cohort study analyzed data from 155 medical schools for 1978 to 2021, which were obtained from the Association of American Medical Colleges. Retention rates were calculated by gender, race and ethnicity, and degree type. Time to attrition was estimated using Kaplan-Meier curves and adjusted Cox proportional hazards models were used to examine the differences in retention by gender and race. Data were analyzed from March 2021 to November 2022. Main Outcomes and Measures The duration of continuous employment in academic medicine and variations in retention based on gender, race, ethnicity, and terminal degree. Results Among 390 766 faculty members (232 829 [59.6%] men; 1190 American Indian, Alaska Native, Native Hawaiian, or Pacific Islander [0.3%]; 72 490 Asian [18.6%]; 14 920 Black [3.8%]; 20 345 Hispanic, Latino, of Spanish origin, or multirace Hispanic [5.2%]; 251 670 non-Hispanic White [64.4%] participants; and 30 151 [7.7%] other race), 259 628 (66.4%) had MD or MD-equivalent terminal degrees. Women left academic medicine a median of 1 year earlier (median retention, 8.33 years; 95% CI, 8.18-8.41 years) than men (median retention, 9.35 years; 95% CI, 9.25-9.42 years). Compared with White faculty (median retention, 9.91 years; 95% CI, 9.83-9.92 years), multiracial and faculty of other races had the lowest retention (median retention, 5.42 years; 95% CI, 5.33-5.55 years), followed by Alaska Native, American Indian, Native Hawaiian, and Pacific Islander (median retention, 6.00 years; 95% CI, 5.62-6.62 years), Black (median retention, 7.78 years; 95% CI, 7.50-8.00 years), Asian (median retention, 8.00 years; 95% CI, 8.00-8.11 years) and Hispanic faculty (median retention, 9.00 years; 95% CI, 8.75-9.16 years). Women faculty in the 1970s were 20% more likely than men to leave academia, whereas women in the 2010s had no greater risk of leaving, mainly due to a decline in retention of men. Conclusions and Relevance Gender differences in faculty retention have decreased in the most recent decade; however, men had lower retention compared with earlier cohorts. In this study, faculty who were underrepresented in medicine left academic medicine a median of 1 to 4 years earlier than White faculty. Greater attrition among men and women for recent cohorts suggests that enhanced retention efforts are imperative to maintain an experienced and diverse faculty.
A Glimpse at Transplant Outcomes From Kidney Donors After Extended Times to Circulatory Death—Might We Be Turning Away Too Soon?
Authors: Emily A. Vail, Matthew D. Bacchetta
Journal: JAMA Network Open (2024)

Samuel J. Tingle, MBBS; Nicholas D. H. Chung, MBBS; Abdullah K. Malik, MBBS; Georgios Kourounis, MBBS; Emily Thompson, PhD; Emily K. Glover, MBBS; Jennifer Mehew, PhD; Jennifer Philip, MD; Dale Gardiner, MBBS; Gavin J. Pettigrew, PhD; Chris Callaghan, PhD; Neil S. Sheerin, PhD; Colin H. Wilson, PhD
Why Evidence Generation Should Matter to Payers
Authors: Joshua Hauser, Rita F. Redberg
Journal: JAMA (2024)

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Xenotransplantation
Authors: Leonardo V. Riella
Journal: Journal of the American Society of Nephrology (2024)

1Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 2Nephrology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School aCorrespondence: Dr. Leonardo Riella, MD PhD ([email protected]), 55 Fruit St, Boston, MA 02114
Early physiologic changes after awake prone positioning predict clinical outcomes in patients with acute hypoxemic respiratory failure
Authors: Matias Olmos, Mariano Esperatti, Nora Fuentes, Anabel Miranda Tirado, María Eugenia Gonzalez, Hiromi Kakisu, Juan Suarez, Manuel Tisminetzky, Veronica Barbaresi, Ignacio Santomil, Alejandro Bruhn Cruz, Domenico Luca Grieco, Bruno L Ferreyro
Journal: Intensive Care Medicine (2024)
Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection
Authors: Ting Zhang, Yunfeng Li, Liuliu Pan, Jihui Sha, Michael Bailey, Emmanuelle Faure-Kumar, Christopher Kazu Williams, James Wohlschlegel, Shino Magaki, Chao Niu, Yoojin Lee, Yu-Chyuan Su, Xinmin Li, Harry V Vinters, Daniel H Geschwind
Journal: Nature Aging (2024)
Rapid response of lichen planus to baricitinib associated with suppression of cytotoxic CXCL13+ CD8+ T-cells
Authors: Angelina S. Hwang, Jacob A. Kechter, Tran H. Do, Alysia N. Hughes, Nan Zhang, Xing Li, Rachael Bogle, Caitlin M. Brumfiel, Meera H. Patel, Blake Boudreaux, Puneet Bhullar, Shams Nassir, Miranda L. Yousif, Alyssa L. Stockard, Zachary Leibovit-Reiben, Ewoma Ogbaudu, David J. DiCaudo, Jennifer Fox, Mehrnaz Gharaee-Kermani, Xianying Xing, Samantha Zunich, Emily Branch, J. Michelle Kahlenberg, Allison C. Billi, Olesya Plazyo, Lam C. Tsoi, Mark R. Pittelkow, Johann E. Gudjonsson, Aaron R. Mangold
Journal: Journal of Clinical Investigation (2024)

Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon gamma (IFN)-γ, a cytokine implicated in the pathogenesis of LP.