tbuckley/cabot-search huggingface dataset:
National Estimates of Short- and Longer-Term Hospital Readmissions After Major Surgery Among Community-Living Older Adults
Authors: Yi Wang, Linda Leo-Summers, Brent Vander Wyk, Kendra Davis-Plourde, Thomas M. Gill, Robert D. Becher
Journal: JAMA Network Open (2024)

Importance Nationally representative estimates of hospital readmissions within 30 and 180 days after major surgery, including both fee-for-service and Medicare Advantage beneficiaries, are lacking. Objectives To provide population-based estimates of hospital readmission within 30 and 180 days after major surgery in community-living older US residents and examine whether these estimates differ according to key demographic, surgical, and geriatric characteristics. Design, Setting, and Participants A prospective longitudinal cohort study of National Health and Aging Trends Study data (calendar years 2011-2018), linked to records from the Centers for Medicare &amp;amp;amp; Medicaid Services (CMS). Data analysis was conducted from April to August 2023. Participants included community-living US residents of the contiguous US aged 65 years or older who had at least 1 major surgery from 2011 to 2018. Data analysis was conducted from April 10 to August 28, 2023. Main Outcomes and Measures Major operations and hospital readmissions within 30 and 180 days were identified through data linkages with CMS files that included both fee-for-service and Medicare Advantage beneficiaries. Data on frailty and dementia were obtained from the annual National Health and Aging Trends Study assessments. Results A total of 1780 major operations (representing 9 556 171 survey-weighted operations nationally) were identified from 1477 community-living participants; mean (SD) age was 79.5 (7.0) years, with 56% being female. The weighted rates of hospital readmission were 11.6% (95% CI, 9.8%-13.6%) for 30 days and 27.6% (95% CI, 24.7%-30.7%) for 180 days. The highest readmission rates within 180 days were observed among participants aged 90 years or older (36.8%; 95% CI, 28.3%-46.3%), those undergoing vascular surgery (45.8%; 95% CI, 37.7%-54.1%), and persons with frailty (36.9%; 95% CI, 30.8%-43.5%) or probable dementia (39.0%; 95% CI, 30.7%-48.1%). In age- and sex-adjusted models with death as a competing risk, the hazard ratios for hospital readmission within 180 days were 2.29 (95% CI, 1.70-3.09) for frailty and 1.58 (95% CI, 1.15-2.18) for probable dementia. Conclusions and Relevance In this nationally representative cohort study of community-living older US residents, the likelihood of hospital readmissions within 180 days after major surgery was increased among older persons who were frail or had probable dementia, highlighting the potential value of these geriatric conditions in identifying those at increased risk.
Therapeutic Hypothermia in Low-Risk Nonpumped Brain-Dead Kidney Donors
Authors: Madhukar S. Patel, Juan D. Salcedo-Betancourt, Christina Saunders, Kristine Broglio, Darren Malinoski, Claus U. Niemann
Journal: JAMA Network Open (2024)

Importance Delayed graft function in kidney-transplant recipients is associated with increased financial cost and patient burden. In donors with high Kidney Donor Profile Index whose kidneys are not pumped, therapeutic hypothermia has been shown to confer a protective benefit against delayed graft function. Objective To determine whether hypothermia is superior to normothermia in preventing delayed graft function in low-risk nonpumped kidney donors after brain death. Design, Setting, and Participants In a multicenter randomized clinical trial, brain-dead kidney donors deemed to be low risk and not requiring machine perfusion per Organ Procurement Organization protocol were prospectively randomized to hypothermia (34.0-35 °C) or normothermia (36.5-37.5 °C) between August 10, 2017, and May 21, 2020, across 4 Organ Procurement Organizations in the US (Arizona, Upper Midwest, Pacific Northwest, and Texas). The final analysis report is dated June 15, 2022, based on the data set received from the United Network for Organ Sharing on June 2, 2021. A total of 509 donors (normothermia: n = 245 and hypothermia: n = 236; 1017 kidneys) met inclusion criteria over the study period. Intervention Donor hypothermia (34.0-35.0 °C) or normothermia (36.5-37.5 °C). Main Outcomes and Measures The primary outcome was delayed graft function in the kidney recipients, defined as the need for dialysis within the first week following kidney transplant. The primary analysis follows the intent-to-treat principle. Results A total of 934 kidneys were transplanted from 481 donors, of which 474 were randomized to the normothermia group and 460 to the hypothermia group. Donor characteristics were similar between the groups, with overall mean (SD) donor age 34.2 (11.1) years, and the mean donor creatinine level at enrollment of 1.03 (0.53) mg/dL. There was a predominance of Standard Criteria Donors (98% in each treatment arm) with similar low mean (SD) Kidney Donor Profile Index (normothermia: 28.99 [20.46] vs hypothermia: 28.32 [21.9]). Cold ischemia time was similar in the normothermia and hypothermia groups (15.99 [7.9] vs 15.45 [7.63] hours). Delayed graft function developed in 87 of the recipients (18%) in the normothermia group vs 79 (17%) in the hypothermia group (adjusted odds ratio, 0.92; 95% CI, 0.64-1.33; P = .66). Conclusions and Relevance The findings of this study suggest that, in low-risk non-pumped kidneys from brain-dead kidney donors, therapeutic hypothermia compared with normothermia does not appear to prevent delayed graft function in kidney transplant recipients. Trial Registration ClinicalTrials.gov Identifier: NCT02525510
Novel Polygenic Risk Score and Established Clinical Risk Factors for Risk Estimation of Aortic Stenosis
Authors: Aeron M. Small, Giorgio E. M. Melloni, Frederick K. Kamanu, Brian A. Bergmark, Marc P. Bonaca, Michelle L. O’Donoghue, Robert P. Giugliano, Benjamin M. Scirica, Deepak Bhatt, Elliott M. Antman, Itamar Raz, Stephen D. Wiviott, Buu Truong, Peter W. F. Wilson, Kelly Cho, Christopher J. O’Donnell, Eugene Braunwald, Steve A. Lubitz, Patrick Ellinor, Gina M. Peloso, Christian T. Ruff, Marc S. Sabatine, Pradeep Natarajan, Nicholas A. Marston
Journal: JAMA Cardiology (2024)

Polygenic risk scores (PRSs) have proven to be as strong as or stronger than established clinical risk factors for many cardiovascular phenotypes. Whether this is true for aortic stenosis remains unknown.
Monocyte NLRP3 inflammasome and interleukin-1β activation modulated by alpha-1 antitrypsin therapy in deficient individuals
Authors: Debananda Gogoi, Howard Yu, Michelle Casey, Rory Baird, Azeez Yusuf, Luke Forde, Michael E O' Brien, Jesse R West, Tammy Flagg, Noel G McElvaney, Edward Eden, Christian Mueller, Mark L Brantly, Patrick Geraghty, Emer P Reeves
Journal: Thorax (2024)

Altered complement component 3 (C3) activation in patients with alpha-1 antitrypsin (AAT) deficiency (AATD) has been reported. To understand the potential impact on course of inflammation, the aim of this study was to investigate whether C3d, a cleavage-product of C3, triggers interleukin (IL)-1β secretion via activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. The objective was to explore the effect of AAT augmentation therapy in patients with AATD on the C3d/complement receptor 3 (CR3) signalling axis of monocytes and on circulating pro-inflammatory markers.
Multi‐omics analysis of disulfidptosis regulators and therapeutic potential reveals glycogen synthase 1 as a disulfidptosis triggering target for triple‐negative breast cancer
Authors: Jindong Xie, Xinpei Deng, Yi Xie, Hongbo Zhu, Peng Liu, Wei Deng, Li Ning, Yuhui Tang, Yuying Sun, Hailin Tang, Manbo Cai, Xiaoming Xie, Yutian Zou
Journal: MedComm (2024)

Disruption of disulfide homeostasis during biological processes can have fatal consequences. Excess disulfides induce cell death in a novel manner, termed as "disulfidptosis." However, the specific mechanism of disulfidptosis has not yet been elucidated. To determine the cancer types sensitive to disulfidptosis and outline the corresponding treatment strategies, we firstly investigated the crucial functions of disulfidptosis regulators pan-cancer at multi-omics levels. We found that different tumor types expressed dysregulated levels of disulfidptosis regulators, most of which had an impact on tumor prognosis. Moreover, we calculated the disulfidptosis activity score in tumors and validated it using multiple independent datasets. Additionally, we found that disulfidptosis activity was correlated with classic biological processes and pathways in various cancers. Disulfidptosis activity was also associated with tumor immune characteristics and could predict immunotherapy outcomes. Notably, the disulfidptosis regulator, glycogen synthase 1 (
Serious Brain Injuries Tied to Higher Brain Cancer Risk in US Veterans
Authors: Emily Harris
Journal: JAMA (2024)

Moderate or severe traumatic brain injuries (TBIs), along with penetrating TBIs, were linked with a higher risk of brain cancer among US veterans who served in the Afghanistan and Iraq wars, a cohort study of 1.9 million veterans found. The data came from medical records from 2004 to 2019.
Blind Spots, Shortcuts, and Automation Bias—Researchers Are Aiming to Improve AI Clinical Models
Authors: Jennifer Abbasi, Yulin Hswen
Journal: JAMA (2024)

This Medical News article is an interview with University of Michigan computer scientist Jenna Wiens, whose research interests lie at the intersection of AI and health care, and JAMA Editor in Chief Kirsten Bibbins-Domingo.
The importance of British Sign Language
Authors: Kirsten Abioye
Journal: BMJ (2024)

Kirsten Abioye describes the huge role that British Sign Language plays in her family and the impact of health professionals not having this skill Kirsten AbioyeMy son failed his newborn hearing screening, but further tests told us he was able to hear.Throughout the next two and a half years he was frustrated a lot of the time and relied heavily on routines.He had no speech and huge delays in understanding.Not long before he turned 3, an audit of our paediatric audiology department found many children had been misdiagnosed, and further testing found him to be profoundly deaf.We quickly started to learnBritish Sign Language (BSL), which has given our family the ability to have unabridged communication.We finally all speak the same language.
Limitations of Reporting Requirements under California’s Livestock Antimicrobial Restriction Law
Authors: Sebastian Quaade, Joan A. Casey, Keeve E. Nachman, Sara Y. Tartof, Daniel E. Ho
Journal: Environmental Health Perspectives (2024)

Antimicrobial use in livestock production is considered a key contributor to growing antimicrobial resistance in bacteria. In 2015, California became the first state to enact restrictions on routine antimicrobial use in livestock production via Senate Bill 27 (SB27). SB27 further required the California Department of Food and Agriculture (CDFA) to collect and disseminate data on antimicrobial use in livestock production.
Influence of co-mutational patterns in disease phenotype and clinical outcomes of chronic myelomonocytic leukemia
Authors: Guillermo Montalban-Bravo, Juan Jose Rodriguez-Sevilla, David Michael Swanson, Rashmi Kanagal-Shamanna, Danielle Hammond, Kelly Chien, Koji Sasaki, Elias Jabbour, Courtney DiNardo, Koichi Takahashi, Nicholas Short, Ghayas C. Issa, Naveen Pemmaraju, Tapan Kadia, Farhad Ravandi, Naval Daver, Gautam Borthakur, Sanam Loghavi, Sherry Pierce, Carlos Bueso-Ramos, Hagop Kantarjian, Guillermo Garcia-Manero
Journal: Leukemia (2024)
Issue Information
Authors: Daniel Solomon, Richard Bucala, New Haven, Mariana Kaplan, Peter Nigrovic, Boston Co, Karen Costenbader, David Felson, Richard Loeser, Chapel Hill, Amr Sawalha, Susan Boackle, Aileen Davis, Daniel Horton, New Brunswick, Bharat Kumar, Iowa City, Brandon Law, Michelle Ormseth, Suraj Rajasimhan, Kimberly Murphy, Maggie Parry, Georgia Production, Brian Robinson, Chris Reynolds, Georgia Austin, Audra Jenson, Marta Alarcón-Riquelme, Granada Basu, Edward Behrens, Bryce Binstadt, Nunzio Bottini, San Diego, John Carrino, New York, Andrew Cope, Adam Croft, Nicola Dalbeth, Brian Feldman, Richard Furie, Great Neck, J Kahlenberg, Ann Arbor, Benjamin Leder, Yvonne Lee, Katherine Liao, Bing Lu, Stephen Messier, Winston-Salem Rachel, E Miller, Janet Pope, Lisa Rider, Christopher Ritchlin, Rochester Robinson, Carla Scanzello, Georg Schett, Sakae Tanaka, Maria Trojanowska, Betty Tsao, Fredrick Wigley, Edith Williams, Ayaz Aghayev, Joshua Baker, Bonnie Bermas, Jamie Collins, Kristen Demoruelle, Denver Denton, Anisha Dua, John Fitzgerald, Angeles Henderson, Monique Hinchcliff, Hui-Chen Hsu, Mohit Kapoor, Seoyoung Kim, Vasileios Kyttaris, Carl Langefeld, Winston-Salem Dennis Mcgonagle, Julie Paik, Julie Zikherman, San Francisco, American College, O Rheumatology, Deborah Desir, Carol Langford, Anne Bass, William Harvey, Steven Echard
Journal: Arthritis & Rheumatology (2024)
Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis
Authors: Rachel L. Padget, Michael J. Zeitz, Grace A. Blair, Xiaobo Wu, Michael D. North, Mira T. Tanenbaum, Kari E. Stanley, Chelsea M. Phillips, D. Ryan King, Samy Lamouille, Robert G. Gourdie, Gregory S. Hoeker, Sharon A. Swanger, Steven Poelzing, James W. Smyth
Journal: Circulation Research (2024)

BACKGROUND: Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and a resulting lack of mechanistic understanding. Myocarditis is a major cause of sudden cardiac death in young adults, where current knowledge in the field is dominated by later disease phases and pathological immune responses. However, little is known regarding how infection can acutely induce an arrhythmogenic substrate before significant immune responses. Adenovirus is a leading cause of myocarditis, but due to species specificity, models of infection are lacking, and it is not understood how adenoviral infection may underlie sudden cardiac arrest. Mouse adenovirus type-3 was previously reported as cardiotropic, yet it has not been utilized to understand the mechanisms of cardiac infection and pathology. METHODS: We have developed mouse adenovirus type-3 infection as a model to investigate acute cardiac infection and molecular alterations to the infected heart before an appreciable immune response or gross cardiomyopathy. RESULTS: Optical mapping of infected hearts exposes decreases in conduction velocity concomitant with increased Cx43 Ser368 phosphorylation, a residue known to regulate gap junction function. Hearts from animals harboring a phospho-null mutation at Cx43 Ser368 are protected against mouse adenovirus type-3–induced conduction velocity slowing. Additional to gap junction alterations, patch clamping of mouse adenovirus type-3–infected adult mouse ventricular cardiomyocytes reveals prolonged action potential duration as a result of decreased I K1 and I Ks current density. Turning to human systems, we find human adenovirus type-5 increases phosphorylation of Cx43 Ser368 and disrupts synchrony in human induced pluripotent stem cell-derived cardiomyocytes, indicating common mechanisms with our mouse whole heart and adult cardiomyocyte data. CONCLUSIONS: Together, these findings demonstrate that adenoviral infection creates an arrhythmogenic substrate through direct targeting of gap junction and ion channel function in the heart. Such alterations are known to precipitate arrhythmias and likely contribute to sudden cardiac death in acutely infected patients.
Apoptosis, a useful marker in the management of hot‐phase cardiomyopathy?
Authors: Giulia Bassetto, Marco Merlo, Matteo Dal Ferro, Martina Setti, Alessia Paldino, Chiara Collesi, Rebecca Artioli, Francesco Loffredo, Saverio D'Elia, Paolo Golino, Enrico Fabris, Rossana Bussani, Marco Metra, Giuseppe Limongelli, Gianfranco Sinagra
Journal: European Journal of Heart Failure (2024)
Intersectional perspectives of parents of transgender children in Aotearoa (New Zealand)
Authors: Julia de Bres, Ia Morrison-Young
Journal: International Journal of Transgender Health (2024)

This article explores the intersectional perspectives of parents of transgender children in Aotearoa (New Zealand). The substantial body of research on parent experiences in this area has largely focused on parents who are white North American middle-class cisgender women. We seek to extend this research by taking an intersectional approach and examining the perspectives of a group of participants of different genders, sexual orientations, and cultural backgrounds.
Eplontersen: First Approval
Authors: Tina Nie
Journal: Drugs (2024)

Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide directed to TTR, which is being developed by Ionis Pharmaceuticals and AstraZeneca for the treatment of TTR-mediated amyloidosis (ATTR). Eplontersen, which is targeted to the liver by a ligand containing three N-acetyl galactosamine residues, binds to wild-type and variant TTR mRNA, thus reducing the levels of circulating TTR protein and amyloid deposition. Subcutaneous eplontersen reduced serum TTR levels, inhibited neuropathy progression and improved health-related quality of life in patients with polyneuropathy of hereditary ATTR (ATTRv-PN; v for variant) in a phase III trial. Based on these results, eplontersen was approved in the USA for the treatment of ATTRv-PN on 21 December 2023 and is currently undergoing regulatory review for a similar indication in the EU, the UK, Switzerland and Canada. Eplontersen is also undergoing phase III development for ATTR cardiomyopathy. This article summarizes the milestones in the development of eplontersen leading to this first approval for ATTRv-PN.
Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy
Authors: Xiaoxiao Liu, Baolei Li, Shuyun Wang, Erge Zhang, Megan Schultz, Marlin Touma, Andre Monteiro Da Rocha, Sylvia M. Evans, Anne Eichmann, Todd Herron, Ruizhen Chen, Dingding Xiong, Alexander Jaworski, Stephen Weiss, Ming-Sing Si
Journal: Circulation Research (2024)

Recently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression in the cardiovascular system after birth, SLIT3's relevance to cardiovascular function in the postnatal state remains unknown. As such, the objectives of this study were to determine the postnatal myocardial sources of SLIT3 and to evaluate its functional role in regulating the cardiac response to pressure overload stress. We performed in vitro studies on cardiomyocytes and myocardial tissue samples from patients and performed in vivo investigation with SLIT3 and ROBO1 (roundabout homolog 1) mutant mice undergoing transverse aortic constriction to establish the role of SLIT3-ROBO1 in adverse cardiac remodeling. We first found that SLIT3 transcription was increased in myocardial tissue obtained from patients with congenital heart defects that caused ventricular pressure overload. Immunostaining of hearts from WT (wild-type) and reporter mice revealed that SLIT3 is secreted by cardiac stromal cells, namely fibroblasts and vascular mural cells, within the heart. Conditioned media from cardiac fibroblasts and vascular mural cells both stimulated cardiomyocyte hypertrophy in vitro, an effect that was partially inhibited by an anti-SLIT3 antibody. Also, the N-terminal, but not the C-terminal, fragment of SLIT3 and the forced overexpression of SLIT3 stimulated cardiomyocyte hypertrophy and the transcription of hypertrophy-related genes. We next determined that ROBO1 was the most highly expressed roundabout receptor in cardiomyocytes and that ROBO1 mediated SLIT3's hypertrophic effects in vitro. In vivo, Tcf21+ fibroblast and Tbx18+ vascular mural cell-specific knockout of SLIT3 in mice resulted in decreased left ventricular hypertrophy and cardiac fibrosis after transverse aortic constriction. Furthermore, α-MHC+ cardiomyocyte-specific deletion of ROBO1 also preserved left ventricular function and abrogated hypertrophy, but not fibrosis, after transverse aortic constriction. Collectively, these results indicate a novel role for the SLIT3-ROBO1-signaling axis in regulating postnatal cardiomyocyte hypertrophy induced by pressure overload.
Age barriers in allogeneic hematopoietic cell transplantation: Raising the silver curtain
Authors: Pashna N. Munshi, Shannon R. McCurdy
Journal: American Journal of Hematology (2024)

Allogeneic hematopoietic cell transplantation (HCT) is no longer exclusively for the young. With an aging population, development of non-intensive remission-inducing strategies for hematologic malignancies, and novel graft-versus-host disease-prevention platforms, an older population of patients is pursuing HCT. The evolving population of HCT recipients requires an overhaul in the way we risk-stratify and optimize patients prior to HCT. Here, we review the history and current state of HCT for older adults and propose an assessment and intervention flow to bridge the gaps in today's clinical guidelines.
Hand2 Immunohistochemistry in the Diagnosis of Paragangliomas and Other Neuroendocrine Neoplasms
Authors: Jiri Soukup, Monika Manethova, Vaclav Stejskal, Marie Novakova, Jaroslava Duskova, Helena Hornychova, Maria Hacova, Iva Staniczkova-Zambo, Tomas Zelinka, Mikulas Kosak, Tomas Cesak, David Netuka, Ales Ryska, Filip Gabalec
Journal: Endocrine Pathology (2024)
Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis
Authors: Jiaorong Qu, Le Wang, Yufei Li, Xiaojiaoyang Li
Journal: Clinical and Molecular Hepatology (2024)

Liver sinusoidal endothelial cells (LSECs) are liver-specific endothelial cells with the highest permeability than other mammalian endothelial cells, characterized by the presence of fenestrae on their surface, the absence of diaphragms and the lack of basement membrane. Located at the interface between blood and other liver cell types, LSECs mediate the exchange of substances between the blood and the Disse space, playing a crucial role in maintaining substance circulation and homeostasis of multicellular communication. As the initial responders to chronic liver injury, the abnormal LSEC activation not only changes their own physicochemical properties but also interrupts their communication with hepatic stellate cells and hepatocytes, which collectively aggravates the process of liver fibrosis. In this review, we have comprehensively updated the various pathways by which LSECs were involved in the initiation and aggravation of liver fibrosis, including but not limited to cellular phenotypic change, the induction of capillarization, decreased permeability and regulation of intercellular communications. Additionally, the intervention effects and latest regulatory mechanisms of anti-fibrotic drugs involved in each aspect have been summarized and discussed systematically. As we studied deeper into unraveling the intricate role of LSECs in the pathophysiology of liver fibrosis, we unveil a promising horizon that pave the way for enhanced patient outcomes.