tbuckley/cabot-search huggingface dataset:
Gastric Bypass Versus Sleeve Gastrectomy in Type 2 Diabetes: Effects on Hepatic Steatosis and Fibrosis
Authors: Kathrine Aglen Seeberg, Heidi Borgeraas, Dag Hofsø, Milada Cvancarova Småstuen, Nils Petter Kvan, John Olav Grimnes, Morten Lindberg, Farhat Fatima, Lars Thomas Seeberg, Rune Sandbu, Jøran Hjelmesæth, Jens Kristoffer Hertel
Journal: Annals of Internal Medicine (2021)

Weight loss improves fatty liver disease. No randomized trial has compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on liver fat content and fibrosis.To compare the 1-year effects of SG and RYGB on hepatic steatosis and fibrosis.Single-center, randomized, controlled trial (Oseberg [ObesitySurgery in Tønsberg]). (ClinicalTrials.gov: NCT01778738).Tertiary care obesity center in Norway.100 patients (65% female; mean age, 47.5 years; mean body mass index, 42 kg/m2) with type 2 diabetes mellitus (T2DM).From January 2013 to February 2018, patients were randomly assigned (1:1 ratio) to SG or RYGB.The primary outcome was remission of T2DM (previously published). Predefined secondary outcomes in the present study were hepatic steatosis and fibrosis assessed by magnetic resonance imaging (liver fat fraction), enhanced liver fibrosis (ELF) test, noninvasive indices, and liver enzymes.Liver fat fraction declined similarly after SG (-19.7% [95% CI, -22.5% to -16.9%]) and RYGB (-21.5% [CI, -24.3% to -18.6%]) from surgery to 1-year follow-up, and almost all patients (SG, 94%; RYGB, 100%) had no or low-grade steatosis at 1 year. The ELF score category remained stable in 77% of patients, but 18% experienced worsening of fibrosis at 1 year, with no substantial between-group difference.Single-center study, short follow-up time, and lack of power for secondary outcomes.With an almost complete clearance of liver fat 1 year after surgery, RYGB and SG were both highly effective in reducing hepatic steatosis. Bariatric surgery had less influence on degree of fibrosis in the short term, but assessment of long-term progression is warranted.Vestfold Hospital Trust and the South-Eastern Norway Regional Health Authority.
In This Issue
Journal: Blood Cancer Discovery (2022)

B-precursor acute lymphoblastic leukemia (B-ALL) relapse often involves the central nervous system (CNS).In this article, Vanner, Dobson, et al. characterize B-ALL subclones with differential CNS involvement in patient-derived xenografts.By comparing transcriptional profiles, the authors identify complement component C3 and stem cell, metabolic, and mRNA translation pathways enriched in subclones with preferential CNS residence regardless of mutational composition.These findings are validated by proteomics and by genetic or pharmacologic targeting of the candidate pathways.The protein translation inhibitor omacetaxine mepesuccinate strongly reduces CNS infiltration.
Polygenic Ara-C Response Score Identifies Pediatric Patients With Acute Myeloid Leukemia in Need of Chemotherapy Augmentation
Authors: Abdelrahman H. Elsayed, Xueyuan Cao, Amit K. Mitra, Huiyun Wu, Susana Raimondi, Christopher Cogle, Zeina Al-Mansour, Raul C. Ribeiro, Alan Gamis, Edward Anders Kolb, Richard Aplenc, Todd A. Alonzo, Soheil Meshinchi, Jeffrey Rubnitz, Stanley Pounds, Jatinder K. Lamba
Journal: Journal of Clinical Oncology (2022)

PURPOSE To establish a patient-specific polygenic score derived from cytarabine (ara-C) pathway pharmacogenomic evaluation to personalize acute myeloid leukemia (AML) treatment. MATERIALS AND METHODS Single nucleotide polymorphisms (SNPs) in the ara-C-pathway genes were analyzed with outcome in patients from the multicenter-AML02 trial (N = 166). Multi-SNP predictor modeling was used to develop 10-SNP Ara-C_SNP score (ACS10) using top SNPs predictive of minimal residual disease and event-free survival (EFS) from the AML02-cohort and four SNPs previously associated with ara-C triphosphate levels in the AML97 trial. ACS10 was evaluated for association with outcomes in each clinical trial arms: the standard low-dose ara-C (LDAC, n = 91) and augmented high-dose ara-C (HDAC, n = 75) arms of AML02 and the standard Ara-C, daunorubicin and etoposide (ADE) (n = 465) and the augmented ADE + gemtuzumab ozogamicin (GO; n = 466) arms of AAML0531 trial. RESULTS In the standard LDAC-arm of AML02 cohort, the low-ACS10 score group (≤ 0) had significantly worse EFS (ACS10 low v high hazard ratio [HR] = 2.81; 95% CI, 1.45 to 5.43; P = .002) and overall survival (OS; HR = 2.98; 95% CI, 1.32 to 6.75; P = .009) compared with the high-ACS10 group (score &gt; 0). These results were validated in the standard-ADE arm of AAML0531, with poor outcome in the low-ASC10 group compared with the high-ACS10 group (EFS: HR = 1.35, 95% CI, 1.04 to 1.75, P = .026; OS: HR = 1.64, 95% CI, 1.2 to 2.22, P = .002). Within the augmented arms (AML02-HDAC and AAML0531-ADE + GO), EFS and OS did not differ between low- and high-ACS10 score groups. In both cohorts, patients with low-ACS10 consistently showed a 10-percentage point improvement in 5-year EFS with augmented therapy (AML02-HDAC or AAML0531-ADE + GO arms) than with standard therapy (AML02-LDAC or AAML0531-ADE arms). CONCLUSION Patients with low-ACS10 score experienced significantly poor outcome when treated on standard regimen. Augmentation with either high-dose ara-C or GO addition improved outcome in low-ACS10 group. A polygenic ACS10 score can identify patients with unfavorable pharmacogenetic characteristics and offers a potential for an elective augmented therapy option.
Melanocortin 4 receptor stimulation prevents antidepressant-associated weight gain in mice caused by long-term fluoxetine exposure
Authors: María José Ortuño, Marc Schneeberger, Anoj Ilanges, François Marchildon, Kyle Pellegrino, Jeffrey M. Friedman, Patricia Ducy
Journal: Journal of Clinical Investigation (2021)

Contrasting with the predicted anorexigenic effect of increasing brain serotonin signaling, long-term use of selective serotonin reuptake inhibitor (SSRI) antidepressants correlates with body weight (BW) gain. This adverse outcome increases the risk of transitioning to obesity and interferes with treatment compliance. Here, we show that orally administered fluoxetine (Flx), a widely prescribed SSRI, increased BW by enhancing food intake in healthy mice at 2 different time points and through 2 distinct mechanisms. Within hours, Flx decreased the activity of a subset of brainstem serotonergic neurons by triggering autoinhibitory signaling through 5-hydroxytryptamine receptor 1a (Htr1a). Following a longer treatment period, Flx blunted 5-hydroxytryptamine receptor 2c (Htr2c) expression and signaling, decreased the phosphorylation of cAMP response element-binding protein (CREB) and STAT3, and dampened the production of pro-opiomelanocortin (POMC, the precursor of α-melanocyte stimulating hormone [α-MSH]) in hypothalamic neurons, thereby increasing food intake. Accordingly, exogenous stimulation of the melanocortin 4 receptor (Mc4r) by cotreating mice with Flx and lipocalin 2, an anorexigenic hormone signaling through this receptor, normalized feeding and BW. Flx and other SSRIs also inhibited CREB and STAT3 phosphorylation in a human neuronal cell line, suggesting that these noncanonical effects could also occur in individuals treated long term with SSRIs. By defining the molecular basis of long-term SSRI-associated weight gain, we propose a therapeutic strategy to counter this effect.
Lenalidomide and the Expanding Toolkit to Manage Kaposi Sarcoma
Authors: David H. Henry, Robert G. Maki
Journal: Clinical Cancer Research (2022)

Summary Lenalidomide recently was shown to have clinical activity in patients with human immunodeficiency virus—associated Kaposi sarcoma. Immunomodulatory imine drugs thus provide another tool in the treatment of this challenging neoplasm. See related article by Reid et al., p. 2646
Reply to Kalverda <i>et al.</i>: Endobronchial Optical Coherence Tomography: Shining New Light on Diagnosing Usual Interstitial Pneumonitis?
Authors: Sreyankar Nandy, Rebecca A. Raphaely, Ashok Muniappan, Angela Shih, Benjamin W. Roop, Amita Sharma, Colleen M. Keyes, Thomas V. Colby, Hugh G. Auchincloss, Henning A. Gaissert, Michael Lanuti, Christopher R. Morse, Harald C. Ott, John C. Wain, Cameron D. Wright, Maria L. Garcia-Moliner, Maxwell L. Smith, Paul A. VanderLaan, Sarita R. Berigei, Mari Mino-Kenudson, Nora K. Horick, Lloyd L. Liang, Diane L. Davies, Margit V. Szabari, Peter Caravan, Benjamin D. Medoff, Andrew M. Tager, Melissa J. Suter, Lida P. Hariri
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
COVID-19 Vaccine in Patients with Exacerbation of Idiopathic Pulmonary Fibrosis
Authors: Giacomo Sgalla, Tonia Magrì, Marialessia Lerede, Alessia Comes, Luca Richeldi
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

can be drawn from our clinical observations, we anticipate that this important topic will be further explored in future longitudinal, prospective studies.In conclusion, our observations suggest that COVID-19 vaccination may act as a potential trigger of AE-IPF, warranting a close monitoring strategy of IPF patients after vaccination to early detect worsening of symptoms or oxygen desaturation, requiring immediate clinical referral.While COVID-19 vaccination remains strongly advised in the general IPF population, further evidence is required to clarify whether a clinical phenotype of IPF could be at higher risk of acute exacerbation following vaccine administration.
Treatment Trials in Young Patients with Chronic Obstructive Pulmonary Disease and Pre–Chronic Obstructive Pulmonary Disease Patients: Time to Move Forward
Authors: Fernando J. Martinez, Alvar Agusti, Bartolome R. Celli, MeiLan K. Han, James P. Allinson, Surya P. Bhatt, Peter Calverley, Sanjay H. Chotirmall, Badrul Chowdhury, Patrick Darken, Carla A. Da Silva, Gavin Donaldson, Paul Dorinsky, Mark Dransfield, Rosa Faner, David M. Halpin, Paul Jones, Jerry A. Krishnan, Nicholas Locantore, Fernando D. Martinez, Hana Mullerova, David Price, Klaus F. Rabe, Colin Reisner, Dave Singh, Jørgen Vestbo, Claus F. Vogelmeier, Robert A. Wise, Ruth Tal-Singer, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene-environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: "young" individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider "young" patients with COPD those patients in the age range of 20-50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in
Eosinophils protect pressure overload- and β-adrenoreceptor agonist-induced cardiac hypertrophy
Authors: Chongzhe Yang, Jie Li, Zhiyong Deng, Songyuan Luo, Jing Liu, Wenqian Fang, Feng Liu, Tianxiao Liu, Xian Zhang, Yuanyuan Zhang, Zhaojie Meng, Shuya Zhang, Jianfang Luo, Conglin Liu, Dafeng Yang, Lijun Liu, Galina K Sukhova, Anastasiia Sadybekov, Vsevolod Katritch, Peter Libby, Jing Wang, Junli Guo, Guo-Ping Shi
Journal: Cardiovascular Research (2022)

Abstract Aims Blood eosinophil (EOS) counts and EOS cationic protein (ECP) levels associate positively with major cardiovascular disease (CVD) risk factors and prevalence. This study investigates the role of EOS in cardiac hypertrophy. Methods and results A retrospective cross-section study of 644 consecutive inpatients with hypertension examined the association between blood EOS counts and cardiac hypertrophy. Pressure overload- and β-adrenoreceptor agonist isoproterenol-induced cardiac hypertrophy was produced in EOS-deficient ΔdblGATA mice. This study revealed positive correlations between blood EOS counts and left ventricular (LV) mass and mass index in humans. ΔdblGATA mice showed exacerbated cardiac hypertrophy and dysfunction, with increased LV wall thickness, reduced LV internal diameter, and increased myocardial cell size, death, and fibrosis. Repopulation of EOS from wild-type (WT) mice, but not those from IL4-deficient mice ameliorated cardiac hypertrophy and cardiac dysfunctions. In ΔdblGATA and WT mice, administration of ECP mEar1 improved cardiac hypertrophy and function. Mechanistic studies demonstrated that EOS expression of IL4, IL13, and mEar1 was essential to control mouse cardiomyocyte hypertrophy and death and cardiac fibroblast TGF-β signalling and fibrotic protein synthesis. The use of human cardiac cells yielded the same results. Human ECP, EOS-derived neurotoxin, human EOS, or murine recombinant mEar1 reduced human cardiomyocyte death and hypertrophy and human cardiac fibroblast TGF-β signalling. Conclusion Although blood EOS counts correlated positively with LV mass or LV mass index in humans, this study established a cardioprotective role for EOS IL4 and cationic proteins in cardiac hypertrophy and tested a therapeutic possibility of ECPs in this human CVD.
Baltimore Wins Lasker–Koshland Award
Journal: Cancer Discovery (2021)

The Albert and Mary Lasker Foundation has bestowed its prestigious Lasker-Koshland Award for Special Achievement in Medical Science upon David Baltimore, PhD, president emeritus and distinguished professor of biology at the California Institute of Technology (Caltech) in Pasadena, and 1975 Nobel Laureate in Physiology or Medicine, calling him "one of the premier biomedical scientists of the last five decades."
Outcomes Associated With Peripheral Artery Disease in Myocardial Infarction With Cardiogenic Shock
Authors: Nino Mihatov, Ramya C. Mosarla, Ajay J. Kirtane, Sahil A. Parikh, Kenneth Rosenfield, Siyan Chen, Yang Song, Robert W. Yeh, Eric A. Secemsky
Journal: Journal of the American College of Cardiology (2022)
Decreased Fatty Acid Oxidation and Altered Lactate Production during Exercise in Patients with Post-acute COVID-19 Syndrome
Authors: Esther de Boer, Irina Petrache, Nir M. Goldstein, J. Tod Olin, Rebecca C. Keith, Brian Modena, Michael P. Mohning, Zulma X. Yunt, Inigo San-Millán, Jeffrey J. Swigris
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial
Authors: Bo Xu, Shengxian Tu, Lei Song, Zening Jin, Bo Yu, Guosheng Fu, Yujie Zhou, Jian’an Wang, Yundai Chen, Jun Pu, Lianglong Chen, Xinkai Qu, Junqing Yang, Xuebo Liu, Lijun Guo, Chengxing Shen, Yaojun Zhang, Qi Zhang, Hongwei Pan, Xiaogang Fu, Jian Liu, Yanyan Zhao, Javier Escaned, Yang Wang, William F Fearon, Kefei Dou, Ajay J Kirtane, Yongjian Wu, Patrick W Serruys, Weixian Yang, William Wijns, Changdong Guan, Martin B Leon, Shubin Qiao, Gregg W Stone
Journal: The Lancet (2021)
Abstract EP55: Qualitative Evaluation Of Older Adult Participants Of A Community Outreach Telehealth Program For Covid Education And Health Promotion (Coach)
Authors: Michelle C Yang, Cam Clayton, Devin Harris, Chelsea Pelletier, Julia Schmidt, Jill G Zwicker, Brodie Sakakibara
Journal: Circulation (2022)

Background: Chronic diseases are prevalent in Canada’s aging population (≥65 years). Positive health behaviours (e.g., physical activity, healthy diet) are critical for the management of chronic diseases (e.g., stroke, heart disease). However, novel coronavirus (COVID-19) prevention strategies of quarantining, social isolation, and physical distancing may compromise one's ability to manage health and engage in daily activities, possibly increasing risk of adverse health events. The Community Outreach teleheAlth program for Covid education and Health promotion (COACH) program has demonstrated an increase in health promoting behaviours, but little is known about participants’ experiences in participating in the program. The program entailed six telehealth sessions over two months that focused on health coaching, behaviour change, and COVID education. The objectives of this study were to describe: (1) chronic disease prevention and management strategies of older adults (≥65 years of age) during COVID-19; and (2) participants’ experience in COACH sessions delivered by medical students at the University of British Columbia. Methods: Twenty-four COACH participants participated in semi-structured interviews that were conducted through Zoom videoconferencing. Interview questions focused on how participants managed their own health before and during COVID-19. Qualitative description was the guiding methodological framework. Interviews were transcribed verbatim and analyzed thematically. Findings: Participants’ mean age was 73.4 years (58% female) with 75% reporting two or more chronic conditions (e.g., stroke, heart disease, coronary artery disease, diabetes, heart attack). Three themes described participants’ prevention and management strategies, including: i) having a purpose for optimizing health; ii) using internal self-control strategies; and iii) leveraging external support strategies. COACH further supported participants during COVID-19, as represented through coach interactions as well as knowledge and skill development. Conclusion: Findings suggest that older adults engage in internal self-control strategies and external support means to manage current chronic conditions and promote health and well-being. Health professional program students have a potential role in health promotion and in assuming the role of coach in telehealth promotion programs for older adults.
Determination of Brain Death
Authors: Gabriel M Danovitch, Francis L Delmonico
Journal: New England Journal of Medicine (2022)

In existence for more than three years, ATAC has promoted the education of the lay public and medical professionals, established a transplant "hot line", and raised substantial funds, all for the sole purpose of promoting and facilitating organ and tissue transplantation.Very recently, the California Department of Health and Welfare, through administrative channels, authorized Medi-Cal benefits for heart transplant recipients.Heart transplants no longer carry the "experimental" label with them.
Abstract P163: Gut Microbiome And Stages Of Diabetes In Middle-aged Adults: CARDIA Microbiome Study
Authors: Yi-Han Hu, Katie Meyer, Anju Lulla, Osorio Meirelles, Lenore J Launer
Journal: Circulation (2022)

Background: Animal and human studies suggest the gut microbiome may be linked to insulin resistance and to diabetes. Results from population-based studies are limited and different stages of diabetes in relation to the gut microbiome have not been investigated. Objective: Examine cross-sectional associations of insulin resistance (IR), duration of diabetes, and 4 stages of diabetes (normoglycemic, prediabetes, and diabetes with (+) and without (-) anti-diabetic medication) with gut microbiome community composition in the Coronary Artery Risk Development in Young Adults (CARDIA). Method: The analysis is based on 605 Black and White participants who attended CARDIA’s Year 30 follow-up examination (2015-2016; aged 48-60 years). Using previously described methods, DNA from stool samples was sequenced using 16S rRNA method. We included 3 genus-level gut microbiome composition measures: alpha-diversity (Shannon index and richness), beta-diversity (Bray-Curtis dissimilarity matrix, PERMANOVA test), and taxonomy. For the analysis, the HOMA-IR levels at Years 25 and 30 were averaged; and diabetes duration was calculated as the sum of years starting at the Year 2 exam. Multivariable-adjusted regressions were used to assess associations of diabetes-related exposures with microbial features, adjusting for socio-demographics, clinical measures, health behaviors, and medication use. Genus-specific analysis was adjusted for multiple comparisons using a false discovery rate (FDR), with significance set to q-value &lt;0.1. Results: Among 605 participants, 20% had prediabetes, and 15% had diabetes (9% on anti-diabetic medication treatment) at Year 30. Compared to those without diabetes, richness and Shannon index were inversely associated with diabetes duration and diabetes with treatment but not with HOMA-IR or prediabetes. PERMANOVA tests were significant for all diabetes-related exposures (p-values&lt;0.05). After multivariable and FDR adjustment, 3 genera (all negative associations) were associated with HOMA-IR, 22 genera (2 positive associations) with diabetes duration, and 4 genera (1 positive association) with diabetes+. No genera were associated with prediabetes. There was reduced abundance of several butyrate producers in participants with higher HOMA-IR (ex., Lachnospiraceae_UGG.004 and Veillonella ), longer diabetes duration (ex., Agathobacter and Ruminococcus ), or diabetes+ (ex., Agathobacter and Romboutsia) . Conclusion: This study indicates significant associations of the gut microbiota composition with glycemic control and insulin resistance, which can contribute to our understanding of diabetes pathophysiology and its prevention and management. Certain butyrate-producing bacteria may play a beneficial role in glucose metabolism and insulin regulation. Future studies with longer-term follow-ups are warranted to explore the relevant mechanisms.
High-Flow Nasal Cannula Failure Odds Is Largely Independent of Duration of Use in COVID-19
Authors: Hayley B. Gershengorn, Ivan Pavlov, Yonatan Perez, Elsa Tavernier, Miguel Ibarra-Estrada, David Vines, Bairbre McNicholas, Oriol Roca, Stephan Ehrmann, John G. Laffey, Jie Li
Journal: American Journal of Respiratory and Critical Care Medicine (2022)