tbuckley/cabot-search huggingface dataset:
Abstract 13086: Left Atrial Function in Adult With Normally Functioning Bicuspid Aortic Valves
Authors: Mingxing XIE, Deng Wenhui, Wang Jing
Journal: Circulation (2020)

Background: Bicuspid aortic valve is a complicated and heterogeneous disease that has aroused great interest in recent years. Traditionally the greatest attention during a routine echocardiography is paid to the function of the ventricles and aortopathy, much less is known about dysfunction the left atrium. The objective of this study was to characterize left atrial strain (LAS) and functions by two-dimensional speckle tracking echocardiography in adult BAV with normally functioning, and interrogate the risk factors. Methods: This is a prospective cohort study of 52 patients (age 40.23±11.29 years) and 33 healthy volunteers (aged 39.12±12.74 years) were recruited. All subjects included in both groups were in sinus rhythm and no clinical history of cardiovascular diseases. We mainly assessed left atrial reservoir, pump, and conduit function using 2D STE, then determined relationships among indices of segmental aortic stiffening, BAV cusp fusion pattern, LV diastolic function indices and LA deformation. Results: Without adjustment, the indices of LA functions in patients with BAV were significantly decreased compared with controls (LAS 49.41 ± 11.14 vs 59.48 ± 9.53, p&lt;0.001, LAEF 71.56 ± 6.57 vs 76.36 ± 5.72, p=0.001; LAS-passive 29.43 ± 9.42 vs 36.67 ± 9.60, p=0.001, LAEF-passive 43.72 ± 10.78 vs 49.58 ± 6.80, p=0.003). However, after adjustment on age, gender, systolic blood pressure, diastolic blood pressure, BSA ,only the LAS was lowering (p&lt;0.001). With or without adjustment, the ascending aorta of patients with BAV were still stiffer at each segment compared with controls. As parameters of LV diastolic functions, the E/e’ ratio (p=0.01) and e’ value (p=0.01) were significantly altered. The LA volume were increased in BAV patients (59.33 ± 19.12 vs 46.10 ± 9.73). In patients with BAV, LA functions, LV functions and segmental aortic stiffness were not influenced by the Sivere valve types. In multiple regression analysis, the stiffness at the sinus of Valsalva were independently correlated with LAS (adjust R 2 = 0.82, β = -0.33, p&lt;0.001). Conclusion: Left atrial dysfunction is common in adult BAV with normally functioning. LA dysfunction is associated with stiffness index at the sinus of Valsalva, and is independent of LV function.
Anticoagulation at the End of Life
Authors: Anna L. Parks, Kenneth E. Covinsky
Journal: JAMA Internal Medicine (2021)

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Sex-Based Dimorphism of Anticancer Immune Response and Molecular Mechanisms of Immune Evasion
Authors: Fabio Conforti, Laura Pala, Eleonora Pagan, Vincenzo Bagnardi, Tommaso De Pas, Paola Queirolo, Elisabetta Pennacchioli, Chiara Catania, Emilia Cocorocchio, Pier Francesco Ferrucci, Maristella Saponara, Gianmarco Orsolini, Paola Zagami, Eleonora Nicoló, Filippo De Marinis, Giampaolo Tortora, Emilio Bria, Saverio Minucci, Hadine Joffe, Paolo Veronesi, Jennifer Wargo, Rachel Rosenthal, Charles Swanton, Alberto Mantovani, Richard D. Gelber, Giuseppe Viale, Aron Goldhirsch, Giuseppe Giaccone
Journal: Clinical Cancer Research (2021)

We previously demonstrated that sex influences response to immune checkpoint inhibitors. In this article, we investigate sex-based differences in the molecular mechanisms of anticancer immune response and immune evasion in patients with NSCLC.We analyzed (i) transcriptome data of 2,575 early-stage NSCLCs from seven different datasets; (ii) 327 tumor samples extensively characterized at the molecular level from the TRACERx lung study; (iii) two independent cohorts of 329 and 391 patients, respectively, with advanced NSCLC treated with anti-PD-1/anti-PD-L1 drugs.As compared with men, the tumor microenvironment (TME) of women was significantly enriched for a number of innate and adaptive immune cell types, including specific T-cell subpopulations. NSCLCs of men and women exploited different mechanisms of immune evasion. The TME of females was characterized by significantly greater T-cell dysfunction status, higher expression of inhibitory immune checkpoint molecules, and higher abundance of immune-suppressive cells, including cancer-associated fibroblasts, MDSCs, and regulatory T cells. In contrast, the TME of males was significantly enriched for a T-cell-excluded phenotype. We reported data supporting impaired neoantigens presentation to immune system in tumors of men, as molecular mechanism explaining the findings observed. Finally, in line with our results, we showed significant sex-based differences in the association between TMB and outcome of patients with advanced NSCLC treated with anti-PD-1/PD-L1 drugs.We demonstrated meaningful sex-based differences of anticancer immune response and immune evasion mechanisms, that may be exploited to improve immunotherapy efficacy for both women and men.
Abstract 15272: Estimating Life Expectancy of Systolic Blood Pressure Intervention Trial Participants Using Pooled Epidemiologic Cohort Data
Authors: Brandon Bellows, Yiyi Zhang, Zugui Zhang, Donald M Lloyd-jones, Adam P Bress, Jordan B King, Paul Kolm, WILLIAM CUSHMAN, Karen Johnson, Leonardo Tamariz, Elizabeth Oelsner, Steven Shea, Anne B Newman, Diane G Ives, David Couper, Andrew E Moran, William S Weintraub
Journal: Circulation (2020)

Introduction: Intensive systolic blood pressure (SBP) treatment (&lt;120 mm Hg) in the Systolic Blood Pressure Intervention Trial (SPRINT) improved overall survival compared to standard treatment (&lt;140 mm Hg). Economic analyses of SPRINT require extrapolation of treatment effects beyond the trial data. Methods: We projected life expectancy after SPRINT using six US cohort studies in the National Heart, Lung, and Blood Institute Pooled Cohorts Study (NHLBI-PCS). We included SPRINT-eligible NHLBI-PCS participants as those aged &gt;=50 years with SBP 130-180 mm Hg and increased cardiovascular disease (CVD) risk without diabetes or history of stroke. We used propensity scores to weight NHLBI-PCS participants to resemble SPRINT participants. In SPRINT participants, we estimated in-trial survival (&lt;4 years) using a time-based flexible parametric survival model (FPSM). In SPRINT-eligible NHLBI-PCS participants, we estimated post-trial survival (&gt;=4 years) using an age-based FPSM and applied the formula to SPRINT participants to predict post-trial survival. We combined in- and post-trial survival to project overall life expectancy for each SPRINT participant and compared it to commonly used Gompertz methods. Results: We included 8,584 SPRINT and 10,610 SPRINT-eligible NHLBI-PCS participants. After propensity weighting, mean (SD) age was 67.9 (9.4) and 68.7 (8.8) years, 35.5% and 38.3% were female in SPRINT and NHLBI-PCS, respectively. Predicted in-trial survival was similar to that observed in SPRINT with both FPSM and Gompertz models (Figure). Assuming constant treatment effects, projected mean life expectancy using the NHLBI-PCS method was 21.1 (7.4) years with intensive and 19.3 (7.2) years with standard treatment; compared to 11.2 (2.3) and 10.5 (2.2) years, respectively, using the Gompertz method. Conclusions: Combining SPRINT and NHLBI-PCS observed data may offer a more realistic estimate of life expectancy than by parametrically extrapolating SPRINT data.
Abstract 17253: The Late Sodium Current Contributes to Electromechanical Defects Occurring With Aging
Authors: Daniel O Cervantes, Emanuele Pizzo, Martina Comelli, Aaron Plosker, Bridget Faltas, Eleonora Cianflone, Peter J Mohler, Thomas J Hund, Jason T Jacobson, Marcello Rota
Journal: Circulation (2020)

To establish the contribution of the late sodium current (I NaL ) on cardiovascular defects occurring with aging, mice with phosphomimetic mutation of Na + channel Nav1.5 at Ser571 (S571E), which causes I NaL enhancement in cardiomyocytes (I NaL gain-of-function), and mice with ablation of the Nav1.5 Ser571 (S571A), preventing CaMKII-mediated I NaL increase under stress condition (I NaL loss-of-function) were studied together with C57Bl/6 mice (wild-type, WT). Male mice at 2-6 (~4 m), 10-16 (~12 m), 17-20 (~18 m), and 20-27 (~24 m) months of age underwent electrocardiographic and echocardiographic evaluation. In WT mice, the QT interval duration of the ECG in the anesthetized state was similar at ~4 and ~12 months (56±5 ms and 58±5 ms, respectively) and was prolonged at ~18 and ~24 months (66±4 ms and 67±3 ms, respectively). In S571E mice, QT interval at ~4 months was prolonged with respect to WT animals (67±4 ms) and remained protracted at ~12, ~18, and ~24 months (65±3 ms, 68±6 ms, and 69±5 ms). S571A animals at ~4 months presented intermediate QT interval duration with respect to the other two strains (61±3 ms), and remained unchanged at ~12, ~18, and ~24 months (63±4 ms, 62±4 ms, and 64±4 ms). Ejection fraction was not altered with age and was comparable for the three mouse groups. In contrast, by transmitral flow Doppler echocardiography diastolic function, quantified here by the isovolumic relaxation time, was normal in WT mice at ~4 (17.4±1.6 ms) and ~12 months (16.8±1.6 ms) and became depressed at ~18 (21.5±2.5 ms) and ~24 months (21.4±1.7 ms). Defective diastolic function was apparent in S571E mice at ~4 months (19.7±2.9 ms) and persisted at ~12, ~18, and ~24 months (19.1±1.7 ms, 21.0±1.9 ms, and 22.1±2.2 ms, respectively). Interestingly, S571A mice at ~4 months had normal diastolic function (16.2±2.2 ms) and minor alterations were observed at ~12, ~18, and ~24 months (17.1±1.5 ms, 18.4±1.6 ms, and 19.3±3.3 ms, respectively). Overall, collected results suggest that I NaL enhancement in S571E mice is associated with premature appearance of prolonged electrical recovery and defective diastolic function, with respect to aging WT animals. In contrast, S571A mice, with inability to increase I NaL , are protected from electromechanical defects occurring with aging.
Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer
Authors: Peter S. Hall, Daniel Swinson, David A. Cairns, Justin S. Waters, Russell Petty, Christine Allmark, Sharon Ruddock, Stephen Falk, Jonathan Wadsley, Rajarshi Roy, Tania Tillett, Jonathan Nicoll, Sebastian Cummins, Joseph Mano, Simon Grumett, Zuzana Stokes, Konstantinos-Velios Kamposioras, Anirban Chatterjee, Angel Garcia, Tom Waddell, Kamalnayan Guptal, Nick Maisey, Mohammed Khan, Jo Dent, Simon Lord, Ann Crossley, Eszter Katona, Helen Marshall, Heike I. Grabsch, Galina Velikova, Pei Loo Ow, Catherine Handforth, Helen Howard, Matthew T. Seymour, Eleanor James, Sue Cheeseman, Tom Roques, Nick Reed, Charles Candish, David Fyfe, Kim Last, Richard Ellis, Lesley Samuel, Rebecca Herbertson, Louise Medley, Kinnari Patel, David Sherriff, Angus Robinson, Pavel Bezecny, Dunca Wilkins, Adam McGeoch, Daniel Propper, Olwyn Williams, Serena Hilman, Sherif Raouf, Claire Hobbs, Jo Parkinson, Nick Wadd, W Saku, Victori Kunene, Colin Askill, Arshad Jamil, Emma Cattell, Lauren Gorf, Vallipuram Vigneswaran, Erica Beaumont, Syed Zubair, Elin Jones, Nicholas Reed, Alaaeldin Shablak, George Bozas, Sheela Rao, Michael Bennet, Joanne Askey, Gareth Griffiths, Sally Clive, Vanessa Potter, Jean Gall, Chris Twelves, Matt Sydes, Juan Valle, Jo Webster, Marc Jones, Fiona Collinson, Julia Brown, Louise Brook
Journal: JAMA Oncology (2021)

Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap.
Bifunctional Therapeutic Peptide Assembled Nanoparticles Exerting Improved Activities of Tumor Vessel Normalization and Immune Checkpoint Inhibition
Authors: Mohammad Taleb, Mona Atabakhshi‐Kashi, Yazhou Wang, Hamideh Rezvani Alanagh, Zeinab Farhadi Sabet, Fenfen Li, Keman Cheng, Chen Li, Yingqiu Qi, Guangjun Nie, Zhao Ying
Journal: Advanced Healthcare Materials (2021)

Abstract The effectiveness of cancer immunotherapy is impaired by the dysfunctional vasculature of tumors. Created hypoxia zones and limited delivery of cytotoxic immune cells help to have immune resistance in tumor tissue. Structural and functional normalization of abnormal tumor vasculature provide vessels for more perfusion efficiency and drug delivery that result in alleviating the hypoxia in the tumor site and increasing infiltration of antitumor T cells. Taking advantage of peptide amphiphiles, herein, a novel peptide amphiphile nanoparticle composed of an antiangiogenic peptide (FSEC) and an immune checkpoint blocking peptide ( D PPA) is designed and characterized. FSEC peptide is known to be involved in vessel normalization of tumors in vivo. D PPA is an inhibitory peptide of the PD‐1/PD‐L1 immune checkpoint pathway. The peptide amphiphile nanoparticle sets out to test whether simultaneous modulation of tumor vasculature and immune systems in the tumor microenvironment has a synergistic effect on tumor suppression. Increased intratumoral infiltration of immune cells following vascular normalization, and simultaneously blocking the immune checkpoint function of PD‐L1 reactivates effective immune responses to the tumors. In summary, the current study provides a new perspective on the regulation of tumor vessel normalization and immunotherapy based on functional peptide nanoparticles as nanomedicine for improved therapeutic purposes.
Abstract 15232: Lifetime Risk of Nontraumatic Lower-extremity Amputation: The Atherosclerosis Risk in Communities Study
Authors: Ning Ding, Yejin Mok, Yingying Sang, Maya Salameh, Weihong Tang, Elizabeth Selvin, Kenneth R Butler, Gerardo M HEISS, Kunihiro Matsushita
Journal: Circulation (2020)

Introduction: Nontraumatic lower-extremity amputation is a serious clinical outcome. Major risk factors include peripheral artery disease and diabetic neuropathy. Although incidence rates of amputation have been reported, no lifetime risk estimates are available. Hypothesis: The lifetime risk of amputation is higher in men, blacks, and those of low socioeconomic status (SES). Methods: In 15,744 ARIC participants aged 45-64 at baseline (1987-89), we estimated the lifetime risk of amputation through age 80 by race-sex and race-SES using Fine and Gray’s proportional subhazards model accounting for the competing risk of death. This method is optimal for time-fixed exposures and thus our primary exposures are sex and race. SES included education, annual family income, and the Area Deprivation Index linked to census tract geocoding. Non-traumatic amputation was identified from hospitalization ICD codes (e.g., 84.1, Z89.4) and related operation codes. Results: There were 253 non-traumatic amputations during a median follow up of 29 years. Lifetime risk of amputation at age 80 was highest in black men (4.6%), followed by black women (2.8%), white men (1.1%) and white women (0.7%) ( Figure ). Blacks of low SES showed the highest lifetime risk (4.5%). Blacks with high SES had a higher lifetime risk of amputation than whites with low SES. The pattern was consistent when we investigated each of education (≤ vs. &gt; high school), income (&lt; vs. ≥$25,000) and Area Deprivation Index (&lt; vs. ≥ race-specific median), separately. Conclusions: In this population-based cohort 5% of black men and 3% of black women experienced a non-traumatic amputation during their lifetime, while only 1% of white men and women had a hospitalization for amputation. The lifetime risk was higher among those with lower SES in both race groups. Future public health and primary care efforts should emphasize risk factor management (e.g., diabetes and smoking) among racial minority groups and those with low SES.
혈소판 감소증을 보이는 간경변증 환자에서 간질환의 중증도에 따른 혈청 thrombopoietin의 의의
Authors: 연종은(Jong Eun Yeon), 공휘(Whee Kong), 김지훈(Ji Hoon Kim), 서연석(Yeon Suk Suh), 박상훈(Sang Hoon Park), 권오상(Oh Sang Kwon), 변관수(Kwan Soo Byun), 이창홍(Chang Hong Lee)
Journal: Clinical and Molecular Hepatology (1999)

Background/Aims: Thrombopoietin (TPO) is an important cytokine for megakaryocyte maturation and platelet production. Because the main site of its production is liver, the failing liver may have a role in thrombocytopenia in chronic liver disease. The aims of this study were to determine the serum TPO levels in cirrhotic patients with thrombocytopenia and clarify the relation between the serum TPO levels and liver function impairment. Method: Cirrhotic paitents with thrombocytopenia (LC, n=57, Child class A/B/C; 20/13/24), chronic hepatitis patients (CH, n=24), oncologic patients with thrombocytopenia induced by chemotherapy (HO, n=7), acute viral hepatitis patients (AVH, n=5) and healthy controls (HC, n=5) were enrolled. Serum TPO was measured by an ELISA method. Results: Although the mean platelets counts of LC (69±32, ×103/ul: mean±SD) were lower than those of HC (229±29, ×103/ul), serum TPO levels in LC (108±63 pg/ml: mean±SD) were not significantly different from HC (122±24 pg/ml). In HO, serum TPO was significantly higher than LC (623±746 vs 108±63 pg/ml, p<0.05) inspite of comparable platelets counts. In LC, serum TPO level was not significantly different among Child class groups. It was not correlated with serum ALT, serum albumin levels, prothrombin time, serum bile acid, Child class, Child score and partial thromboplastin time, but weakly correlated with serum total bilirubin (p=0.038, r=0.288) and platelet counts (p=0.041, r=0.287). Conclusions: Although impaired hepatic production of TPO seems to be the main cause of low serum TPO levels in thrombocytopenic cirrhotic patients, there was no correlation between serum TPO level and the severity of liver dysfunction. The role of other factors such as megakaryocyte mass in bone marrow, portal hypertension and hypersplenism may be necessary to explain the putative mechanism between TPO and platelet numbers in liver cirrhosis with thrombocytopenia. (Korean J Hepatol 1999;5:208－216)
Abstract 17039: Angiotensin Converting Enzyme Inhibitors/ Angiotensin Receptor Blockers Decrease Short-Term Mortality in Myocardial Injury After Noncardiac Surgery
Authors: Hanumantha R Jogu, Parag A Chevli, Tareq Islam, Abhishek Dutta, Padageshwar Sunkara, Geeth Sandeep Nadella, Harsh Barot, Luqman-Arafath Thazhathuveetil-Kunhahamed, Chi-Cheng Huang
Journal: Circulation (2020)

Introduction: Myocardial injury after noncardiac surgery (MINS) is strongly associated with 30-day mortality, and no guidelines exist to address management in this group. We hypothesized that Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blocker (ACEI/ARB) reduces short-term mortality in MINS patients. Methods: We used data from the Wake-Up T2MI registry, which is a single-center, retrospective cohort of adults with elevated troponin (cTn) I (&gt;0.04 ng/dL) during hospitalization without acute coronary syndrome in a 2-year period. Kaplan-Meier curve and a multivariate-adjusted Cox-proportional hazard models were performed to assess all-cause mortality at 30-days and 90-days among patients with and without ACEI/ARBs upon discharge. Results: A total of 457 MINS patients were included in the final analysis. There were no significant differences in baseline characteristics and peak cTn among patients stratified by ACEI/ARB status. Prevalence of mortality was significantly lower at 30-days (1.4% vs 6.3%, p = 0.025) and non-significantly lower at 90-days (7.9% vs. 12%, p = 0.188) in patients who were discharged on ACEI/ARBs compared to non-ACEI/ARBs. Patients with ACEI/ARBs upon discharge showed a statistically significant survival benefit at 30-days (log-rank p = 0.023) but not at 90-days (log-rank p = 0.150) (Figure 1). In a multivariate-adjusted model, ACEI/ARBs had a HR of 0.172 (CI: 0.037 - 0.823; p = 0.027) at 30 days and HR of 0.497 (CI: 0.240 - 1.030; p = 0.060) at 90 days (Figure 2). Conclusion: In conclusion, ACEI/ARBs on discharge were associated with decreased short-term mortality in MINS patients. Further studies are needed to validate our results.
Human and preclinical studies of the host–gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health
Authors: François Brial, Julien Chilloux, Trine Nielsen, Sara Vieira-Silva, Gwen Falony, Petros Andrikopoulos, Michael Olanipekun, Lesley Hoyles, Fatima Djouadi, Ana L Neves, Andrea Rodriguez-Martinez, Ghiwa Ishac Mouawad, Nicolas Pons, Sofia Forslund, Emmanuelle Le-chatelier, Aurélie Le Lay, Jeremy Nicholson, Torben Hansen, Tuulia Hyötyläinen, Karine Clément, Matej Oresic, Peer Bork, Stanislav Dusko Ehrlich, Jeroen Raes, Oluf Borbye Pedersen, Dominique Gauguier, Marc-Emmanuel Dumas
Journal: Gut (2021)

Objective Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health. Design In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1 H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes. Results In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion. Conclusion Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.
Long COVID and the brain network of Proust's madeleine: targeting the olfactory pathway
Authors: Eric Guedj, Françoise Lazarini, Silvia Morbelli, Mathieu Ceccaldi, Charlotte Hautefort, Aurélie Kas, Thomas Radulesco, Dominique Salmon-Ceron, Carole Eldin
Journal: Clinical Microbiology and Infection (2021)