tbuckley/cabot-search huggingface dataset:
Antithrombin III Levels and Outcomes Among Patients With Trauma
Authors: David H. Farrell, Keeley M. McConnell, Jevgenia Zilberman-Rudenko, Brandon Behrens, Scott Mcloud, Mackenzie R. Cook, David Martin, John D. Yonge, Samantha J. Underwood, Diane E. Lape, Andrew Goodman, Martin A. Schreiber
Journal: JAMA Network Open (2024)

Importance Patients with trauma exhibit a complex balance of coagulopathy manifested by both bleeding and thrombosis. Antithrombin III is a plasma protein that functions as an important regulator of coagulation. Previous studies have found a high incidence of antithrombin III deficiency among patients with trauma. Objective To assess whether changes in antithrombin III activity are associated with thrombohemorrhagic complications among patients with trauma. Design, Setting, and Participants This cohort study was conducted from December 2, 2015, to March 24, 2017, at a level I trauma center. A total of 292 patients with trauma were followed up from their arrival through 6 days from admission. Data, including quantification of antithrombin III activity, were collected for these patients. Thromboprophylaxis strategy; hemorrhage, deep vein thrombosis (DVT), and pulmonary embolism screenings; and follow-up evaluations were conducted per institutional protocols. Data analyses were performed from September 28, 2023, to June 4, 2024. Main Outcomes and Measures The primary study outcome measurements were associations between antithrombin III levels and outcomes among patients with trauma, including ventilator-free days, hospital-free days, intensive care unit (ICU)–free days, hemorrhage, venous thromboembolic events, and mortality. Results The 292 patients had a mean (SD) age of 54.4 (19.0) years and included 211 men (72.2%). Patients with an antithrombin III deficiency had fewer mean (SD) ventilator-free days (27.8 [5.1] vs 29.6 [1.4]; P = .0003), hospital-free days (20.3 [8.2] vs 24.0 [5.7]; P = 1.37 × 10 −6 ), and ICU-free days (25.7 [4.9] vs 27.7 [2.3]; P = 9.38 × 10 −6 ) compared with patients without a deficiency. Antithrombin III deficiency was also associated with greater rates of progressive intracranial hemorrhage (21.1% [28 of 133] vs 6.3% [10 of 159]; P = .0003) and thrombocytopenia (24.8% [33 of 133] vs 5.0% [8 of 159]; P = 1.94 × 10 −6 ). Although antithrombin III deficiency was not significantly associated with DVT, patients who developed a DVT had a more precipitous decrease in antithrombin III levels that were significantly lower than patients who did not develop a DVT. Conclusions and Relevance In this cohort study of patients with trauma, antithrombin III deficiency was associated with greater injury severity, increased hemorrhage, and increased mortality, as well as fewer ventilator-free, hospital-free, and ICU-free days. Although this was an associative study, these data suggest that antithrombin III levels may be useful in the risk assessment of patients with trauma.
Resilience in the face of neurodivergence: A systematic scoping review of resilience and factors promoting positive outcomes
Authors: Melissa H Black, Johan Helander, Julie Segers, Cecilia Ingard, Jo Bervoets, Vincent Grimaldi de Puget, Sven Bölte
Journal: Clinical Psychology Review (2024)

Neurodivergent individuals, including a range of conditions impacting neurological function, are at an increased likelihood of poor life outcomes, such as in functional adaptation, mental health, and well-being. Yet, many live meaningful and fulfilling lives. Resilience may provide some explanation for the heterogeneity in outcomes observed in neurodivergent populations. We conducted a scoping review embedded in a neurodiversity-affirmative approach to provide an understanding of resilience in neurodivergent populations. A total of 176 articles were included in this review and were synthesized using a two-phased process. First, findings were synthesized narratively to examine how resilience has been conceptualized and explored in neurodivergent populations. Second, to identify the bio-psycho-social factors important for resilience in neurodivergent individuals, we converted concepts identified in articles to the nomenclature of the World Health Organizations' International Classification of Functioning, Disability and Health (ICF) using a standardized linking process. We find considerable variability in how resilience is conceptualized and measured in neurodivergent populations. We identified 83 unique ICF categories representing resilience factors, of which only 20 appeared in more than 5% of the articles. Identified ICF categories highlight the importance of support systems such as families and friends, community participation and acceptance, and individual capabilities for resilience.
International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents
Authors: Ruth T. Casey, Emile Hendriks, Cheri Deal, Steven G. Waguespack, Verena Wiegering, Antje Redlich, Scott Akker, Rathi Prasad, Martin Fassnacht, Roderick Clifton-Bligh, Laurence Amar, Stefan Bornstein, Letizia Canu, Evangelia Charmandari, Alexandra Chrisoulidou, Maria Currás Freixes, Ronald de Krijger, Luisa de Sanctis, Antonio Fojo, Amol J. Ghia, Angela Huebner, Vasilis Kosmoliaptsis, Michaela Kuhlen, Marco Raffaelli, Charlotte Lussey-Lepoutre, Stephen D. Marks, Naris Nilubol, Mirko Parasiliti-Caprino, Henri H.J.L.M. Timmers, Anna Lena Zietlow, Mercedes Robledo, Anne-Paule Gimenez-Roqueplo, Ashley B. Grossman, David Taïeb, Eamonn R. Maher, Jacques W. M. Lenders, Graeme Eisenhofer, Camilo Jimenez, Karel Pacak, Christina Pamporaki
Journal: Nature Reviews Endocrinology (2024)

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork. Teams should ideally include adult and paediatric endocrinologists, oncologists, cardiologists, surgeons, geneticists, pathologists, radiologists, clinical psychologists and nuclear medicine physicians. Provision of an international Consensus Statement should improve care and outcomes for children and adolescents with these tumours.
European Respiratory Society guidelines for the Diagnosis and Management of Pulmonary Alveolar Proteinosis
Authors: Cormac McCarthy, Francesco Bonella, Marissa O'Callaghan, Clairelyne Dupin, Tiago Alfaro, Markus Fally, Raphael Borie, Ilaria Campo, Vincent Cottin, Aurelie Fabre, Matthias Griese, Alice Hadchouel, Stephane Jouneau, Maria Kokosi, Effrosyni Manali, Helmut Prosch, Bruce C. Trapnell, Marcel Veltkamp, Tisha Wang, Ingrid Toews, Alexander G. Mathioudakis, Elisabeth Bendstrup
Journal: European Respiratory Journal (2024)

Background Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxaemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage (BAL), evaluation of antibodies against granulocyte–macrophage colony-stimulating factor (GM-CSF), genetic testing and, eventually, lung biopsy. The management options are focused on removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis and lung transplantation. The presented diagnostic and management guidelines aim to provide guidance to physicians managing patients with PAP. Methods A European Respiratory Society Task Force composed of clinicians, methodologists and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of evidence and strength of recommendations. The Task Force formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions and two narrative questions to develop specific evidence-based recommendations. Results The Task Force developed recommendations for the five PICO questions. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis and lung transplantation. Also, the Task Force made recommendations regarding the use of GM-CSF antibody testing, diagnostic BAL and biopsy based on the narrative questions. In addition to the recommendations, the Task Force provided information on the hierarchy of diagnostic interventions and therapy. Conclusions The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas the diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited.
LPG 18:0 is a general biomarker of asthma and inhibits the differentiation and function of regulatory T cells
Authors: Abudureyimujiang Aili, Yuqing Wang, Ying Shang, Lijiao Zhang, Huan Liu, Zemin Li, Lixiang Xue, Yahong Chen, Yongchang Sun, Xu Zhang, Rong Jin, Chun Chang
Journal: European Respiratory Journal (2024)

Background The diagnosis, severity assessment, and development of therapeutic strategies for asthma are crucial aspects of disease management. Since biomarkers are reliable tools in disease management, we aimed to identify and explore asthma-associated biomarkers and investigate their mechanisms. Methods Lipidomics was used to profile serum glycerophospholipids in asthmatic patients and controls. The absolute concentration of lysophosphatidylglycerol (LPG) 18:0 was quantified in various asthma subtypes. Mouse asthma models were used to confirm its potential as a biomarker and investigate its mechanisms in vivo. The effects of LPG 18:0 on CD4 + T-cell differentiation, proliferation and apoptosis were assessed in vitro by flow cytometry, while mitochondrial dysfunction was evaluated through mitochondrial membrane potential, reactive oxygen species and ATP production measurements. The intracellular mechanism of LPG 18:0 in regulatory T-cells (Tregs) was investigated using small-molecule inhibitors. Results The serum glycerophospholipid profile varied between asthmatic patients and control group, with LPG 18:0 levels being notably higher in asthmatic patients, correlating with asthma severity and control level. In vivo and in vitro studies revealed that LPG 18:0 impaired naïve CD4 + T-cell differentiation into Tregs and compromised their suppressive function. Further investigation demonstrated that LPG 18:0 treatment reduced the FOXP3 protein level via SIRT1-mediated deacetylation during Treg differentiation. Conclusions This study identifies that serum levels of LPG 18:0 are generally elevated in asthmatics and serve as a biomarker for asthma. LPG 18:0 impairs Treg function via the NAD + /SIRT1/FOXP3 pathway. Our research reveals the potential of LPG 18:0 as a biomarker for asthma, elucidating its role in asthma diagnosis and treatment.
Airway derived emphysema-specific alveolar type II cells exhibit impaired regenerative potential in COPD
Authors: Yan Hu, Qianjiang Hu, Meshal Ansari, Kent Riemondy, Ricardo Pineda, John Sembrat, Adriana S. Leme, Kenny Ngo, Olivia Morgenthaler, Kellie Ha, Bifeng Gao, William J. Janssen, Maria C. Basil, Corrine R. Kliment, Edward Morrisey, Mareike Lehmann, Christopher M. Evans, Herbert B. Schiller, Melanie Königshoff
Journal: European Respiratory Journal (2024)

Emphysema, the progressive destruction of gas exchange surfaces in the lungs, is a hallmark of COPD that is presently incurable. This therapeutic gap is largely due to a poor understanding of potential drivers of impaired tissue regeneration, such as abnormal lung epithelial progenitor cells, including alveolar type II (ATII) and airway club cells. We discovered an emphysema-specific subpopulation of ATII cells located in enlarged distal alveolar sacs, termed asATII cells. Single-cell RNA sequencing and in situ localisation revealed that asATII cells co-express the alveolar marker surfactant protein C and the club cell marker secretaglobin-3A2 (SCGB3A2). A similar ATII subpopulation derived from club cells was also identified in mouse COPD models using lineage labelling. Human and mouse ATII subpopulations formed 80–90% fewer alveolar organoids than healthy controls, indicating reduced progenitor function. Targeting asATII cells or their progenitor club cells could reveal novel COPD treatment strategies.
<i>Notes from the Field:</i> Universal Newborn Screening and Surveillance for Congenital Cytomegalovirus — Minnesota, 2023–2024
Authors: Tory Kaye, Elizabeth M. Dufort, Sondra D. Rosendahl, Jenna Hullerman Umar, Amanda Pavan, Karissa Tricas, Lexie Barber, Carrie Wolf, Ruth Lynfield
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Congenital cytomegalovirus (cCMV) is the most frequent infectious cause of birth defects and the most frequent nongenetic cause of permanent hearing loss in U.S. children; cCMV affects approximately 0.5% of U.S. births.Among infants with cCMV infection, approximately 10% have clinical findings at birth (1).Early identification of cCMV infection could improve outcomes through the use of antiviral therapy when indicated, and audiology and developmental screenings (1).A recent Minnesota study found average dried blood spot sensitivity of 75% for detection of cCMV infection (2).In February 2023, Minnesota became the first U.S. state to implement universal newborn screening for cCMV.To evaluate performance and feasibility of newborn screening and to describe the epidemiology of cCMV, statewide surveillance was initiated.This report describes the first year of these activities. Investigation and Outcomes Minnesota Department of Health Newborn Screening RecommendationsUnless parents opt out, all Minnesota-born infants are screened for the presence of cytomegalovirus (CMV) using a qualitative real-time polymerase chain reaction (PCR) assay performed on a dried blood spot at the Minnesota Department of Health.*Infants whose assay detects CMV are recommended to have diagnostic PCR testing, performed on urine, within the first 21 days of life.For infants with diagnosed cCMV, recommended evaluations include complete blood count, liver function testing, neuroimaging, and audiologic and ophthalmologic assessments.In addition, infants with evidence of CMV infection † within the first 90 days of life are voluntarily reported to the Minnesota Department of Health by clinicians or through electronic laboratory reporting.The Minnesota Department of Health newborn screening program follows all identified infants with cCMV to ensure linkage to care and to evaluate long-term outcomes.* https://www.health.state.mn.us/people/newbornscreening/program/ newbornscreeningpanel.pdf† Evidence of CMV infection includes CMV-positive culture, antigen, or nucleic acid amplification testing, from any specimen source.
Pioneering Research Driving Progress toward a Cure for Interstitial Lung Disease (ILD): Introduction to the <i>AJRCCM</i> Special Issue on ILD (Part 2)
Authors: Anna J. Podolanczuk, Toby M. Maher, Wonder P. Drake, Patricia J. Sime, Oliver Eickelberg, Dawn L. DeMeo, Luca Richeldi
Journal: American Journal of Respiratory and Critical Care Medicine (2024)
An Interdisciplinary Consensus Approach to Pulmonary Hypertension in Developmental Lung Disorders
Authors: Nidhy P. Varghese, Eric D. Austin, Csaba Galambos, Mary P. Mullen, Delphine Yung, R. Paul Guillerman, Sara O. Vargas, Catherine M. Avitabile, Corey A. Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O. Jackson, Jill Ann Jarrell, Roberta L. Keller, Usha S. Krishnan, Kalyani R. Patel, Jennifer Pogoriler, Elise C. Whalen, Kathryn A. Wikenheiser-Brokamp, Natalie M. Villafranco, Rachel K. Hopper, J. Usha Raj, Steven H. Abman
Journal: European Respiratory Journal (2024)

It is increasingly recognised that diverse genetic respiratory disorders present as severe pulmonary hypertension (PH) in the neonate and young infant, but many controversies and uncertainties persist regarding optimal strategies for diagnosis and management to maximise long-term outcomes. To better define the nature of PH in the setting of developmental lung disease (DEVLD), in addition to the common diagnoses of bronchopulmonary dysplasia and congenital diaphragmatic hernia, we established a multidisciplinary group of expert clinicians from stakeholder paediatric specialties to highlight current challenges and recommendations for clinical approaches, as well as counselling and support of families. In this review, we characterise clinical features of infants with DEVLD/DEVLD-PH and identify decision-making challenges including genetic evaluations, the role of lung biopsies, the use of imaging modalities and treatment approaches. The importance of working with team members from multiple disciplines, enhancing communication and providing sufficient counselling services for families is emphasised to create an interdisciplinary consensus.
<i>QuickStats:</i> Age-Adjusted Drug Overdose Death* Rates,† by State — United States, 2022
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Not significantly different from the U.S. rate Significantly lower than the U.S. rate Significantly higher than the U.S. rate Abbreviation: DC = District of Columbia.* Drug overdose deaths were identified using International Classification of Diseases, Tenth Revision underlying cause-of-death codes X40-X44, X60-X64, X85, and Y10-Y14
Association between a Recalled Positive Airway Pressure (PAP) Device and Incident Cancer: A Population-Based Study
Authors: Tetyana Kendzerska, Sachin R. Pendharkar, Robert Talarico, Kenneth Blades, Constance Mackenzie, Andrea S. Gershon, Najib Ayas, Marta Kaminska, Mark Fenton, Kerry A. McBrien, Steven Hawken, Diana Ratycz, Vadym Lishchenko, Robert L. Owens, Marcus Povitz
Journal: European Respiratory Journal (2024)

Background The real-world consequences of a Philips Respironics recall for positive airway pressure (PAP) devices distributed between 2009 and 2021 are unknown. Methods We conducted a retrospective population-based study using health administrative databases (Ontario, Canada) on all new adult PAP users identified through the provincial funding system, free of cancer at baseline, who initiated (claimed) PAP treatment between 2012 and 2018. Everyone was followed from the PAP claim date to the earliest of incident cancer diagnosis, death or end of follow-up (March 2022). We used inverse probability of treatment weighting to balance baseline characteristics between individuals on recalled devices and those on devices from other manufacturers. Weighted hazard ratios of incident cancer were compared between groups. Results Of 231 692 individuals identified, 58 204 (25.1%) claimed recalled devices and 173 488 (74.9%) claimed devices from other manufacturers. A meaningful baseline difference between groups (standardised difference ≥0.10) was noted only by location-relevant covariates; other variables were mostly equally distributed (standardised differences ≤0.06). Over a median (interquartile range) follow-up of 6.3 (4.9–8.0) years, 11 166 (4.8%) developed cancer: unadjusted rates per 10 000 person-years of 78.8 (95% CI 76.0–81.7) in the recall group versus 74.0 (95% CI 72.4–75.6) in others (p=0.0034). Propensity score weighting achieved excellent balance in baseline characteristics between groups (standardised differences ≤0.07). On a weighted sample, there was no statistical difference in the hazard of incident cancer between groups: cause-specific hazard ratio (recalled versus others) 0.97 (95% CI 0.89–1.06). Conclusion In our real-world population study, compared to other manufacturers and adjusting for confounders, recalled Philips Respironics PAP devices do not appear to be independently associated with developing cancer.
Exacerbation history and blood eosinophil count prior to diagnosis of COPD and risk of subsequent exacerbations
Authors: David M.G. Halpin, Heath Healey, Derek Skinner, Victoria Carter, Rachel Pullen, David Price
Journal: European Respiratory Journal (2024)

Background Prior exacerbation history is used to guide initial maintenance therapy in COPD; however, the recommendations were derived from patients already diagnosed and treated. Methods We assessed the rates of moderate ( i.e. treated with antibiotics and/or systemic corticosteroids) and severe ( i.e. hospitalised) exacerbations in the year following diagnosis in patients newly diagnosed with COPD according to their prior history of exacerbations, blood eosinophil count (BEC) and whether maintenance therapy was started. Data were extracted from the Optimum Patient Care Research Database. Results 73 189 patients were included. 61.9% had no exacerbations prior to diagnosis, 21.5% had 1 moderate, 16.5% had ≥2 moderate and 0.3% had ≥1 severe. 50% were started on maintenance therapy. In patients not started on maintenance therapy the rates of moderate exacerbations in the year after diagnosis in patients with no, 1 moderate, ≥2 moderate and ≥1 severe prior exacerbations were 0.34 (95% CI 0.33–0.35), 0.59 (95% CI 0.56–0.61), 1.18 (95% CI 1.14–1.23) and 1.21 (95% CI 0.73–1.69), respectively. Similar results were seen in patients started on maintenance therapy. BEC did not add significantly to the prediction of future exacerbation risk. Conclusions A single moderate exacerbation in the year prior to diagnosis increases the risk of subsequent exacerbations, and more frequent or severe exacerbations prior to diagnosis are associated with a higher risk.
Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions
Authors: Lung-Yi Mak, Ken Liu, Sakkarin Chirapongsathorn, Kuo Chao Yew, Nobuharu Tamaki, Ruveena Bhavani Rajaram, Mara Teresa Panlilio, Rashid Lui, Hye Won Lee, Jimmy Che-To Lai, Anand V. Kulkarni, Madhumita Premkumar, Cosmas Rinaldi Adithya Lesmana, Yao Chun Hsu, Daniel Q. Huang
Journal: Nature Reviews Gastroenterology & Hepatology (2024)
Exploring new frontiers in type 1 diabetes through advanced mass-spectrometry-based molecular measurements
Authors: Soumyadeep Sarkar, Xueyun Zheng, Geremy C Clair, Yu Mi Kwon, Youngki You, Adam C Swensen, Bobbie-Jo M Webb-Robertson, Ernesto S Nakayasu, Wei-Jun Qian, Thomas O Metz
Journal: Trends in Molecular Medicine (2024)
A subset of dopamine receptor-expressing neurons in the nucleus accumbens controls feeding and energy homeostasis
Authors: Yiqiong Liu, Ying Wang, Zheng-dong Zhao, Guoguang Xie, Chao Zhang, Renchao Chen, Yi Zhang
Journal: Nature Metabolism (2024)

Abstract Orchestrating complex behaviors, such as approaching and consuming food, is critical for survival. In addition to hypothalamus neuronal circuits, the nucleus accumbens (NAc) also controls appetite and satiety. However, specific neuronal subtypes of the NAc that are involved and how the humoral and neuronal signals coordinate to regulate feeding remain incompletely understood. Here we decipher the spatial diversity of neuron subtypes of the NAc shell (NAcSh) and define a dopamine receptor D1-expressing and Serpinb2- expressing subtype controlling food consumption in male mice. Chemogenetics and optogenetics-mediated regulation of Serpinb2 + neurons bidirectionally regulate food seeking and consumption specifically. Circuitry stimulation reveals that the NAcSh Serpinb2 →LH LepR projection controls refeeding and can overcome leptin-mediated feeding suppression. Furthermore, NAcSh Serpinb2 + neuron ablation reduces food intake and upregulates energy expenditure, resulting in reduced bodyweight gain. Our study reveals a neural circuit consisting of a molecularly distinct neuronal subtype that bidirectionally regulates energy homeostasis, providing a potential therapeutic target for eating disorders.