tbuckley/cabot-search huggingface dataset:
Cost Barriers to More Widespread Use of Peritoneal Dialysis in the United States
Authors: Elliot A. Baerman, Jennifer Kaplan, Jenny I. Shen, Wolfgang C. Winkelmayer, Kevin F. Erickson
Journal: Journal of the American Society of Nephrology (2022)

The United States Department of Health and Human Services launched the Advancing American Kidney Health Initiative in 2019, which included a goal of transforming dialysis care from an in-center to a largely home-based dialysis program. A substantial motivator for this transition is the potential to reduce costs of ESKD care with peritoneal dialysis. Studies demonstrating that peritoneal dialysis is less costly than in-center hemodialysis have often focused on the perspective of the payer, whereas less consideration has been given to the costs of those who are more directly involved in treatment decision making, including patients, caregivers, physicians, and dialysis facilities. We review comparisons of peritoneal dialysis and in-center hemodialysis costs, focusing on costs incurred by the people and organizations making decisions about dialysis modality, to highlight the financial barriers toward increased adoption of peritoneal dialysis. We specifically address misaligned economic incentives, underappreciated costs for key stakeholders involved in peritoneal dialysis delivery, differences in provider costs, and transition costs. We conclude by offering policy suggestions that include improving data collection to better understand costs in peritoneal dialysis, and sharing potential savings among all stakeholders, to incentivize a transition to peritoneal dialysis.
Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021
Authors: Paula B Blomquist, Jessica Bridgen, Neil Bray, Anne Marie O’Connell, Daniel West, Natalie Groves, Eileen Gallagher, Lara Utsi, Christopher I Jarvis, Jo L Hardstaff, Chloe Byers, Soeren Metelmann, David Simons, Asad Zaidi, Katherine A Twohig, Bethan Savagar, Alessandra Løchen, Cian Ryan, Katie Wrenn, María Saavedra-Campos, Zahidul Abedin, Isaac Florence, Paul Cleary, Richard Elson, Roberto Vivancos, Iain R Lake
Journal: Eurosurveillance (2022)

When SARS-CoV-2 Omicron emerged in 2021, S gene target failure enabled differentiation between Omicron and the dominant Delta variant. In England, where S gene target surveillance (SGTS) was already established, this led to rapid identification (within ca 3 days of sample collection) of possible Omicron cases, alongside real-time surveillance and modelling of Omicron growth. SGTS was key to public health action (including case identification and incident management), and we share applied insights on how and when to use SGTS.
Diverse Oncogenic Fusions and Distinct Gene Expression Patterns Define the Genomic Landscape of Pediatric Papillary Thyroid Carcinoma
Authors: Ana Stosic, Fabio Fuligni, Nathaniel D. Anderson, Scott Davidson, Richard de Borja, Meryl Acker, Vito Forte, Paolo Campisi, Evan J. Propst, Nikolaus E. Wolter, Rose Chami, Ozgur Mete, David Malkin, Adam Shlien, Jonathan D. Wasserman
Journal: Cancer Research (2021)

Abstract Pediatric papillary thyroid carcinoma (PPTC) is clinically distinct from adult-onset disease. Although there are higher rates of metastasis and recurrence in PPTC, prognosis remains highly favorable. Molecular characterization of PPTC has been lacking. Historically, only 40% to 50% of childhood papillary thyroid carcinoma (PTC) were known to be driven by genomic variants common to adult PTC; oncogenic drivers in the remainder were unknown. This contrasts with approximately 90% of adult PTC driven by a discrete number of variants. In this study, 52 PPTCs underwent candidate gene testing, followed in a subset by whole-exome and transcriptome sequencing. Within these samples, candidate gene testing identified variants in 31 (60%) tumors, while exome and transcriptome sequencing identified oncogenic variants in 19 of 21 (90%) remaining tumors. The latter were enriched for oncogenic fusions, with 11 nonrecurrent fusion transcripts, including two previously undescribed fusions, STRN-RET and TG-PBF. Most fusions were associated with 3′ receptor tyrosine kinase (RTK) moieties: RET, MET, ALK, and NTRK3. For advanced (distally metastatic) tumors, a driver variant was described in 91%. Gene expression analysis defined three clusters that demonstrated distinct expression of genes involved in thyroid differentiation and MAPK signaling. Among RET-CCDC6–driven tumors, gene expression in pediatric tumors was distinguishable from that in adults. Collectively, these results show that the genomic landscape of pediatric PTC is different from adult PTC. Moreover, they identify genomic drivers in 98% of PPTCs, predominantly oncogenic fusion transcripts involving RTKs, with a pronounced impact on gene expression. Notably, most advanced tumors were driven by a variant for which targeted systemic therapy exists. Significance: This study highlights important distinctions between the genomes and transcriptomes of pediatric and adult papillary thyroid carcinoma, with implications for understanding the biology, diagnosis, and treatment of advanced disease in children.
Anti-CD45RC antibody immunotherapy prevents and treats experimental autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy syndrome
Authors: Marine Besnard, Céline Sérazin, Jason Ossart, Anne Moreau, Nadège Vimond, Léa Flippe, Hanna Sein, Grace A. Smith, Stefania Pittaluga, Elise M.N. Ferré, Claire Usal, Ignacio Anegon, Annamari Ranki, Michail S. Lionakis, Pärt Peterson, Carole Guillonneau
Journal: Journal of Clinical Investigation (2022)

Targeted monoclonal antibody (mAb) therapies show great promise for the treatment of transplant rejection and autoimmune diseases by inducing more specific immunomodulatory effects than broadly immunosuppressive drugs routinely used. We recently described the therapeutic advantage of targeting CD45RC, expressed at high levels by conventional T (Tconv) cells (CD45RChi), their precursors, and terminally differentiated T (TEMRA) cells, but not by regulatory T cells (Tregs; CD45RClo/-). We demonstrated efficacy of anti-CD45RC mAb treatment in transplantation, but its potential has not been examined in autoimmune diseases. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare genetic syndrome caused by loss-of-function mutations of autoimmune regulator (AIRE), a key central tolerance mediator, leading to abnormal autoreactive T cell responses and autoantibody production. Herein, we show that, in a rat model of APECED syndrome, anti-CD45RC mAb was effective for both prevention and treatment of autoimmune manifestations and inhibited autoantibody development. Anti-CD45RC mAb intervention depleted CD45RChi T cells, inhibited CD45RChi B cells, and restored the Treg/Tconv cell ratio and the altered Treg transcriptomic profile. In APECED patients, CD45RC was significantly increased in peripheral blood T cells, and lesioned organs from APECED patients were infiltrated by CD45RChi cells. Our observations highlight the potential role for CD45RChi cells in the pathogenesis of experimental and human APECED syndrome and the potential of anti-CD45RC antibody treatment.
Abstract MP57: Objectively-Assessed Sleep Duration And Incident Heart Failure: The Atherosclerosis Risk In Communities Study-Sleep Heart Health Study
Authors: Brittanny M Polanka, Yasuyuki Honda, Lena Mathews, Amil M Shah, Chiadi E Ndumele, Patricia Chang, Naresh M Punjabi, Pamela L Lutsey, Kuni Matsushita
Journal: Circulation (2022)

Introduction: Evidence is mixed on short sleep duration and heart failure (HF) risk. Notably, no studies have investigated objectively-assessed sleep duration or controlled for comorbid sleep apnea in this context. Objective: To examine the independent associations of objective short sleep duration with incident HF, accounting for sleep apnea. Methods: We studied ARIC-SHHS study participants free of HF at visit 4 (1996-98). Sleep duration was measured by at-home polysomnography (PSG) and defined as: 7 to &lt;9 hours (reference), 6 to &lt;7 hours, 5 to &lt;6 hours, and &lt;5 hours. The apnea-hypopnea index (AHI; defined as: &lt;5, 5 to &lt;15, 15 to &lt;30, and ≥30), a measure of sleep apnea, was also measured by at-home PSG. Cox proportional hazards models, with progressive adjustment for comorbidities and AHI, were used to evaluate the association of sleep duration with incident HF (hospitalizations or deaths with HF diagnosis). Results: We included 1,056 participants (mean age 62 years, 50% female, 99% White). During a median follow-up of 22 years, there were 211 HF events. Participants with sleep duration &lt;5 hours had a higher risk of incident HF in unadjusted and age-sex-adjusted models, with corresponding hazard ratios of 2.44 (95% CI : 1.40-4.26) and 1.88 (95% CI : 1.07-3.29) ( Table ). However, further adjustment for clinical factors attenuated the results. The associations for sleep duration appeared more evident when we restricted our analysis to participants without prevalent cardiovascular disease ( Table ). The AHI was not a significant predictor of incident HF in the presence of sleep duration. Conclusions: Objectively-assessed short sleep duration &lt;5 hours was modestly associated with HF risk. Our study suggests the need and value of larger studies exploring objectively-assessed sleep duration in terms of HF risk. Importantly, sleep duration may be objectively measured without PSG, using wearable devices.
Abstract 11107: Comparison of Left Atrial Appendage Occlusion and Direct Oral Anticoagulants and Warfarin in Patients with Atrial Fibrillation in Russian Prospective Registry
Authors: Irina A Merkulova, Eric A Avetisyan, Olga O Shakhmatova, Vladimir I Ganyukov, Dmitry V Pevzner
Journal: Circulation (2021)

Introduction: Left atrial appendage occlusion (LAAO) is non-inferior to warfarin and direct oral anticoagulants (DOAC) in thromboembolic prophylaxis in atrial fibrillation (AF). However, these antithrombotic strategies in patients with and without contraindications to anticoagulants were not assessed separately before. Hypothesis: LAAO is superior to oral anticoagulants (OAC) in net clinical benefit in patients without contraindications for its usage, and superior to no thromboembolic prophylaxis in patients with contraindications for OAC. Methods: A prospective registry included 379 patients with nonvalvular AF and high risk of thromboembolic events. Patients were assigned into cohorts with and without contraindications to continuous therapy with OAC. In the first cohort patients with LAA occlusion (n=45), on DOAC (n=99) and on warfarin (n=100) were compared. In the second cohort patients with LAAO (n=75) were compared with those who received no antithrombotic prophylaxis (n = 60). The primary composite endpoint was net clinical benefit (all-cause mortality, ischemic stroke/transient ischemic attack/systemic embolism and major bleeding) in 3 years. Results: Using log-rank analysis of Kaplan-Meier curves in the cohort of patients without contraindications to OAC LAAO was superior to warfarin, reaching statistical significance (p=0.048), with a trend towards superiority over DOAC (p=0.061) . In the cohort of patients with contraindications to continuous OAC use, LAAO, in terms of both overall efficacy and safety, was significantly superior to no prophylaxis of thromboembolic events (p=0.003). (Figure 1). Conclusions: LAA occlusion demonstrated superiority to warfarin and no prophylaxis of thromboembolic events in terms of net clinical benefit. There was a trend to superiority of LAAO over DOAC in patients with contraindications to OAC.
81MO Osimertinib as neoadjuvant therapy in patients with EGFR mutated resectable stage II-IIIB lung adenocarcinoma (NEOS): Updated results
Authors: C. Lyu, W. Fang, W. Jiao, H. Ma, J. Wang, S. Xu, N. Wu, R. Wang, Y. Yang
Journal: Annals of Oncology (2022)
Reply to: The potential and challenges of radiomics in uncovering prognostic and molecular differences in interstitial lung disease associated with systemic sclerosis
Authors: Janine Schniering, Malgorzata Maciukiewicz, Stephanie Tanadini-Lang, Britta Maurer
Journal: European Respiratory Journal (2022)

<b>We discuss the pros and cons of radiomics as a novel non-invasive tool to acquire phenotypic, prognostic and molecular information derived from standard-of-care high-resolution computed tomography in patients with ILD.</b>https://bit.ly/36vYyl2
COVID-19 mortality, excess mortality, deaths per million and infection fatality ratio, Belgium, 9 March 2020 to 28 June 2020
Authors: Geert Molenberghs, Christel Faes, Johan Verbeeck, Patrick Deboosere, Steven Abrams, Lander Willem, Jan Aerts, Heidi Theeten, Brecht Devleesschauwer, Natalia Bustos Sierra, Françoise Renard, Sereina Herzog, Patrick Lusyne, Johan Van der Heyden, Herman Van Oyen, Pierre Van Damme, Niel Hens
Journal: Eurosurveillance (2022)

BackgroundCOVID-19 mortality, excess mortality, deaths per million population (DPM), infection fatality ratio (IFR) and case fatality ratio (CFR) are reported and compared for many countries globally. These measures may appear objective, however, they should be interpreted with caution.AimWe examined reported COVID-19-related mortality in Belgium from 9 March 2020 to 28 June 2020, placing it against the background of excess mortality and compared the DPM and IFR between countries and within subgroups.MethodsThe relation between COVID-19-related mortality and excess mortality was evaluated by comparing COVID-19 mortality and the difference between observed and weekly average predictions of all-cause mortality. DPM were evaluated using demographic data of the Belgian population. The number of infections was estimated by a stochastic compartmental model. The IFR was estimated using a delay distribution between infection and death.ResultsIn the study period, 9,621 COVID-19-related deaths were reported, which is close to the excess mortality estimated using weekly averages (8,985 deaths). This translates to 837 DPM and an IFR of 1.5% in the general population. Both DPM and IFR increase with age and are substantially larger in the nursing home population.DiscussionDuring the first pandemic wave, Belgium had no discrepancy between COVID-19-related mortality and excess mortality. In light of this close agreement, it is useful to consider the DPM and IFR, which are both age, sex, and nursing home population-dependent. Comparison of COVID-19 mortality between countries should rather be based on excess mortality than on COVID-19-related mortality.
188P Efficacy of SARS-CoV-2 based mRNA vaccines for patients with thoracic malignancies with 6 months follow up: A prospective observational study
Authors: U. Janzic, K. Mohorcic, L. Mrak, M. Ivanovic, U. Bidovec Stojkovic, J. Debeljak, P. Korosec, M. Rijavec
Journal: Annals of Oncology (2022)
192P Randomized, phase II, placebo-controlled trial of nintedanib for the treatment of radiation pneumonitis
Authors: Z.R. Moore, A. Rimner, S. Lobaugh, A. Geyer, D.Y. Gelblum, A.F. Shepherd, N. Shaverdian, A.J. Wu, J.E. Chaft, M.G. Zauderer, C.M. Rudin, N. Vander Els, M. Chawla, D.R. Jones, D.M. Sopka, R. Mak, Z. Liao, D.R. Gomez, Z. Zhang, P. Paik
Journal: Annals of Oncology (2022)
FDG PET/CT in a Patient With Syphilis Suspected of Having Penile Cancer
Authors: Jakob Kristian Jakobsen, Joanna Szumniak, Christina Stilling, Joan Fledelius, Kirsten Bouchelouche
Journal: Clinical Nuclear Medicine (2022)

A 58-year-old man with large penile wound and enlarged regional lymph node was suspected of having disseminated penile cancer. FDG PET/CT for primary staging showed high FDG uptake on penis and in several enlarged lymph nodes. However, biopsies revealed no signs of malignancy, but ulceration, inflammation, fibrosis, and spirochetes. Furthermore, Wassermann test was positive. The patient was then treated for syphilis. To our knowledge, this is the first report on FDG PET/CT in a patient suspected of having penile cancer that turned out to be syphilis. Thus, syphilis can be added to the list of benign pitfalls in FDG PET/CT.
Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial
Authors: Mary F. Mulcahy, Armeen Mahvash, Marc Pracht, Amir H. Montazeri, Steve Bandula, Robert C. G. Martin, Ken Herrmann, Ewan Brown, Darryl Zuckerman, Gregory Wilson, Tae-You Kim, Andrew Weaver, Paul Ross, William P. Harris, Janet Graham, Jamie Mills, Alfonso Yubero Esteban, Matthew S. Johnson, Constantinos T. Sofocleous, Siddharth A. Padia, Robert J. Lewandowski, Etienne Garin, Philip Sinclair, Riad Salem
Journal: Journal of Clinical Oncology (2021)

To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status.Four hundred twenty-eight patients from 95 centers in North America, Europe, and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity.The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.
Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events
Authors: David R. Jacobs, Jessica G. Woo, Alan R. Sinaiko, Stephen R. Daniels, Johanna Ikonen, Markus Juonala, Noora Kartiosuo, Terho Lehtimäki, Costan G. Magnussen, Jorma S.A. Viikari, Nanhua Zhang, Lydia A. Bazzano, Trudy L. Burns, Ronald J. Prineas, Julia Steinberger, Elaine M. Urbina, Alison J. Venn, Olli T. Raitakari, Terence Dwyer
Journal: New England Journal of Medicine (2022)

Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear. In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression. In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events. In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).
RegVar: Tissue-Specific Prioritization of Non-Coding Regulatory Variants
Authors: Hao Lu, Luyu Ma, Cheng Quan, Lei Li, Yiming Lu, Gangqiao Zhou, Chenggang Zhang
Journal: Genomics Proteomics & Bioinformatics (2021)

Non-coding genomic variants constitute the majority of trait-associated genome variations; however, the identification of functional non-coding variants is still a challenge in human genetics, and a method for systematically assessing the impact of regulatory variants on gene expression and linking these regulatory variants to potential target genes is still lacking. Here, we introduce a deep neural network (DNN)-based computational framework, RegVar, which can accurately predict the tissue-specific impact of non-coding regulatory variants on target genes. We show that by robustly learning the genomic characteristics of massive variant-gene expression associations in a variety of human tissues, RegVar vastly surpasses all current non-coding variant prioritization methods in predicting regulatory variants under different circumstances. The unique features of RegVar make it an excellent framework for assessing the regulatory impact of any variant on its putative target genes in a variety of tissues. RegVar is available as a web server at https://regvar.omic.tech/.
Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease
Authors: Eric Jonasch, Frede Donskov, Othon Iliopoulos, W. Kimryn Rathmell, Vivek K. Narayan, Benjamin L. Maughan, Stephane Oudard, Tobias Else, Jodi K. Maranchie, Sarah J. Welsh, Sanjay  Thamake, Eric K. Park, Rodolfo F. Perini, W. Marston Linehan, Ramaprasad Srinivasan
Journal: New England Journal of Medicine (2021)

Patients with von Hippel–Lindau (VHL) disease have a high incidence of renal cell carcinoma owing to VHL gene inactivation and constitutive activation of the transcription factor hypoxia-inducible factor 2α (HIF-2α).