tbuckley/cabot-search huggingface dataset:
Abstract 15518: Impact of Menopause on Cardiovascular Risk Factors Among Women Without Cardiovascular Disease: Insights From the CARTaGENE Study
Authors: Catherine-Elisabeth Boutet, Maria Lopez Laporte, Ahmed Alturki, Jiayi Ni, Anh Thi Nguyen, Jean-Claude Tardif, Jean C Gregoire, Mark Sherman, Marie-Pierre Dube, Joao Pedro Ferreira, Nadia Giannetti, George Thanassoulis, Abhinav Sharma, Thao Huynh
Journal: Circulation (2020)

Background: The effect of menopausal status on the risk factors of cardiovascular (CV) disease is not well ascertained. We aimed to evaluate the impact of menopause on several traditional and non-traditional cardiovascular (CV) risk factors. Methods: The CARTaGENE study was a prospective cohort study with random sampling of individuals in Quebec, Canada. We completed a seven-year follow-up in 2016. For this analysis, we included only subjects without prior cardiovascular (CV) events (CVE) or CV interventions (CVI). We defined the primary endpoint as CVE which can be any of the following events: acute coronary syndromes, heart failure, strokes, CV deaths, and peripheral vascular events. The secondary endpoint was CVI which included coronary, carotid, or peripheral artery revascularization. We used Cox proportional hazard stepwise multivariate analyses to identify independent predictors of the primary endpoint separately in pre- and post-menopausal women. Results Of 9,529 women without prior CV disease, 57% were post-menopausal. The mean age was 47.4 years and 58.6 years for pre-menopausal and post-menopausal women, respectively. There were 793 CVEs and 83 CVIs with a median time to event of 6.6 years. Hypertension, active smoking, increased waist to hip ratio, and glycosylated hemoglobin were independent predictors of the primary endpoint in both pre- and post-menopausal women. Furthermore, advanced age, family history of myocardial infarction, prior cancer, increased gamma-glutamyl transferase, and hyperuricemia also predicted increased riks of the primary endpoint in post-menopausal women. Conclusion: Hypertension, active smoking, increased waist to hip ratio, and high glycosylated hemoglobin were associated with increased CV risk in pre-menopausal women. The impact of hypertension was markedly amplified in pre-menopausal women compared to postmenopausal women. Intensive blood pressure control should be considered in pre-menopausal women.
The evaluation and management of monoclonal gammopathy of renal significance and monoclonal gammopathy of neurological significance
Authors: Jorge J. Castillo, Natalie S. Callander, Muhamed Baljevic, Douglas W. Sborov, Shaji Kumar
Journal: American Journal of Hematology (2021)

Despite the benign nature of monoclonal gammopathy of undetermined significance (MGUS), mounting data are associating MGUS with the development of organ dysfunction, specifically monoclonal gammopathy of renal significance (MGRS) and monoclonal gammopathy of neurological significance (MGNS), which could be associated with substantial morbidity. Emerging evidence suggests that patients with MGRS and MGNS could benefit from treatments used for myeloma, Waldenström macroglobulinemia, or chronic lymphocytic leukemia, depending on the underlying pathology. However, the treatment of MGRS and MGNS is not standardized, and potentially effective therapies might not be reimbursed because these conditions do not formally meet the criteria for malignant processes. The present review aims at establishing standards for the evaluation and management of MGRS and MGNS, which can facilitate the diagnosis of and provide therapeutic options for treating practitioners and patients affected by these conditions. The careful design and execution of clinical trials for patients with MGRS and MGNS are positively encouraged.
Abstract 13144: Improvement of Left Ventricular Ejection Fraction and Mortality in the Surgical Treatment for Ischemic Heart Failure (STICH) Trial
Authors: Andrew Perry, Aldi T Kraja, Douglas L Mann, David L Brown
Journal: Circulation (2019)

Introduction: Improvement in left ventricular ejection fraction (LVEF) is well-documented in patients with nonischemic cardiomyopathy. However, less is known about the frequency and predictors of L...
Enhanced thrombin/PAR1 activity promotes G-CSF- and AMD3100-induced mobilization of hematopoietic stem and progenitor cells via NO upregulation
Authors: Neta Nevo, Lizeth-Alejandra Ordonez-Moreno, Shiri Gur-Cohen, Francesca Avemaria, Suditi Bhattacharya, Eman Khatib-Massalha, Mayla Bertagna, Montaser Haddad, Priyasmita Chakrabarti, Wolfram Ruf, Tsvee Lapidot, Orit Kollet
Journal: Leukemia (2021)
A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary centre in Israel
Authors: Elad Goldberg, Haim Ben Zvi, Liron Sheena, Summer Sofer, Ilan Krause, Ella H. Sklan, Amir Shlomai
Journal: Clinical Microbiology and Infection (2021)

ObjectivesThe effectiveness of remdesivir, a Food and Drug Administration-approved drug for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been repeatedly questioned during the current coronavirus disease 2019 (COVID-19) pandemic. Most of the recently reported studies were randomized controlled multicentre clinical trials. Our goal was to test the efficiency of remdesivir in reducing nasopharyngeal viral load and hospitalization length in a real-life setting in patients admitted to a large tertiary centre in Israel.MethodsA total of 142 COVID-19 patients found to have at least three reported SARS-CoV-2 quantitative RT-PCR tests during hospitalization were selected for this study. Of these, 29 patients received remdesivir, while the remaining non-treated 113 patients served as controls.ResultsAmong the tested parameters, the control and remdesivir groups differed significantly only in the intubation rates. Remdesivir treatment did not significantly affect nasopharyngeal viral load, as determined by comparing the differences between the first and last cycle threshold values of the SARS-CoV-2 quantitative RT-PCR tests performed during hospitalization (cycle threshold 7.07 ± 6.85 vs. 7.08 ± 7.27, p 0.977 in the control and treated groups, respectively). Remdesivir treatment shortened hospitalization length by less than a day compared with non-treated controls and by 3.1 days when non-intubated patients from both groups were compared. These differences, however, were not statistically significant, possibly because of the small size of the remdesivir group.DiscussionRemdesivir was not associated with nasopharyngeal viral load changes, but our study had a significant disease severity baseline imbalance and was not powered to detect viral load or clinical differences.
Abstract 131: Elevated Serum MPEG-1 Protein is Associated With Reduced Survival and Poor Neurological Recovery in Resuscitated Out-Of-Hospital Sudden Cardiac Arrest
Authors: Sharma Kattel, Hardik Bhatt, Shirley Xu, Saraswati Pokharel, Umesh C Sharma
Journal: Circulation (2019)

Background: For decades, bio-markers involved in inflammation and stress response were implicated in patients who were successfully resuscitated from out of hospital cardiac arrest (sR-OHCA). Here we report that increased serum levels of Macrophage-expressed gene 1 (MPEG1), an evolutionary conserved protein with membrane attack complex domain, is associated with increased mortality and poor neurological outcomes after sR-OHCA. Objectives: To examine the association between circulating MPEG-1 protein measured within the first 6-hours of sR-OHCA, and inpatient survival and neurological outcomes. Methods: We prospectively enrolled 144 sR-OHCA patients from 4 different tertiary care centers. We measured MPEG-1 protein, and other conventional clinical bio-markers including troponin-I and CK-MB in the sera obtained within the first 6-hours of resuscitation. The clinical covariates during hospitalization (till the time death or discharge) were obtained via medical record review. We compared MPEG-1 protein, troponin-I, and CK-MB between survivors vs . non-survivors, and neurological outcomes dichotomized as poor or good according to cerebral performance score (CPS). Results: At the end of the hospital stay, 47% of the patients had poor neurological status based on the CPS score of ≥ 4. Within these patients, 95% had inhospital mortality. The mean serum MPEG-1 levels were significantly higher in patients with poor neurological status, compared to the ones with good neurological recovery (ng/ml, 15.17 ± 48.04 vs 1.15 ± 6.73, p=0.017). There were no differences in other conventionally measured bio-markers, such as peak troponin , CK-MB or left ventricular ejection fraction. Elevated MPEG-1 of more than 8.8 ng/ml had significantly higher odds of predicting poor neurological outcome (OR: 8.37, 95% CI: 1.79-39.14, p=0.006). Conclusions: This study reports a novel macrophage-expressed circulating bio-marker strongly associated with reduced survival and poor neurological outcomes in sR-OHCA. These data can guide clinicians to prognosticate survival and neurological outcomes in sR-OHCA, and also form the basis for future therapeutic approaches.
Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots
Authors: Jacqui Wise
Journal: BMJ (2021)

Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots Jacqui WiseDenmark has temporarily suspended use of the Oxford-AstraZeneca covid-19 vaccine as a precautionary move after reports of blood clots and one death.However, the European Medicines Agency (EMA) and the UK's regulatory body have said that there is no indication that vaccination is linked to thromboembolic events.Eight other countries-Norway, Iceland, Austria, Estonia, Lithuania, Luxembourg, Italy, and Latvia-have also suspended use of AstraZeneca's vaccine.The decisions are a further setback for Europe's vaccination campaign, which has struggled to pick up speed, partly because of delays in delivering the AstraZeneca vaccine.
Gender and Disparity in First Authorship in Cardiology Randomized Clinical Trials
Authors: Roxana Mehran, Ashish Kumar, Agam Bansal, Mariam Shariff, Martha Gulati, Ankur Kalra
Journal: JAMA Network Open (2021)

The current dialogue in cardiovascular medicine is evolving to confer women with equal representation. According to the American College of Cardiology, women represent only 12% of the workforce in cardiology.1 Furthermore, only 9% of the interventional cardiology workforce are women. These numbers extrapolate into academia as well. Although a recent study reported a significant increase in the trend toward female first and senior authors in the cardiology peer-reviewed literature over the past 2 decades, the percentage has remained markedly low.2 This disparity was further substantiated by another study3 that highlighted the underrepresentation of women as first authors in heart failure randomized clinical trials (RCTs). The current literature lacks evidence on female first authors in cardiology RCTs over the past several years. The present study evaluated the annual proportions and overall trend of female first authors in cardiology RCTs from 2011 to 2020.
Integrative Genomic Analysis of Gemcitabine Resistance in Pancreatic Cancer by Patient-derived Xenograft Models
Authors: Gang Yang, Wenfang Guan, Zhe Cao, Wenbo Guo, Guangbing Xiong, Fangyu Zhao, Mengyu Feng, Jiangdong Qiu, Yueze Liu, Michael Q. Zhang, Lei You, Taiping Zhang, Yupei Zhao, Jin Gu
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Gemcitabine is most commonly used for pancreatic cancer. However, the molecular features and mechanisms of the frequently occurring resistance remain unclear. This work aims at exploring the molecular features of gemcitabine resistance and identifying candidate biomarkers and combinatorial targets for the treatment. Experimental Design: In this study, we established 66 patient-derived xenografts (PDXs) on the basis of clinical pancreatic cancer specimens and treated them with gemcitabine. We generated multiomics data (including whole-exome sequencing, RNA sequencing, miRNA sequencing, and DNA methylation array) of 15 drug-sensitive and 13 -resistant PDXs before and after the gemcitabine treatment. We performed integrative computational analysis to identify the molecular networks related to gemcitabine intrinsic and acquired resistance. Then, short hairpin RNA–based high-content screening was implemented to validate the function of the deregulated genes. Results: The comprehensive multiomics analysis and functional experiment revealed that MRPS5 and GSPT1 had strong effects on cell proliferation, and CD55 and DHTKD1 contributed to gemcitabine resistance in pancreatic cancer cells. Moreover, we found miR-135a-5p was significantly associated with the prognosis of patients with pancreatic cancer and could be a candidate biomarker to predict gemcitabine response. Comparing the molecular features before and after the treatment, we found that PI3K-Akt, p53, and hypoxia-inducible factor-1 pathways were significantly altered in multiple patients, providing candidate target pathways for reducing the acquired resistance. Conclusions: This integrative genomic study systematically investigated the predictive markers and molecular mechanisms of chemoresistance in pancreatic cancer and provides potential therapy targets for overcoming gemcitabine resistance.
Health data poverty: an assailable barrier to equitable digital health care
Authors: Hussein Ibrahim, Xiaoxuan Liu, Nevine Zariffa, Andrew D Morris, Alastair K Denniston
Journal: The Lancet Digital Health (2021)

Data-driven digital health technologies have the power to transform health care. If these tools could be sustainably delivered at scale, they might have the potential to provide everyone, everywhere, with equitable access to expert-level care, narrowing the global health and wellbeing gap. Conversely, it is highly possible that these transformative technologies could exacerbate existing health-care inequalities instead. In this Viewpoint, we describe the problem of health data poverty: the inability for individuals, groups, or populations to benefit from a discovery or innovation due to a scarcity of data that are adequately representative. We assert that health data poverty is a threat to global health that could prevent the benefits of data-driven digital health technologies from being more widely realised and might even lead to them causing harm. We argue that the time to act is now to avoid creating a digital health divide that exacerbates existing health-care inequalities and to ensure that no one is left behind in the digital era.
The serum metabolome of COVID-19 patients is distinctive and predictive
Authors: Ding Shi, Ren Yan, Longxian Lv, Huiyong Jiang, Yingfeng Lu, Jifang Sheng, Jiaojiao Xie, Wenrui Wu, Jiafeng Xia, Kaijin Xu, Silan Gu, Yanfei Chen, Chenjie Huang, Jing Guo, Yiling Du, Lanjuan Li
Journal: Metabolism (2021)

Metabolism is critical for sustaining life, immunity and infection, but its role in COVID-19 is not fully understood.Seventy-nine COVID-19 patients, 78 healthy controls (HCs) and 30 COVID-19-like patients were recruited in a prospective cohort study. Samples were collected from COVID-19 patients with mild or severe symptoms on admission, patients who progressed from mild to severe symptoms, and patients who were followed from hospital admission to discharge. The metabolome was assayed using gas chromatography-mass spectrometry.Serum butyric acid, 2-hydroxybutyric acid, l-glutamic acid, l-phenylalanine, l-serine, l-lactic acid, and cholesterol were enriched in COVID-19 and COVID-19-like patients versus HCs. Notably, d-fructose and succinic acid were enriched, and citric acid and 2-palmitoyl-glycerol were depleted in COVID-19 patients compared to COVID-19-like patients and HCs, and these four metabolites were not differentially distributed in non-COVID-19 groups. COVID-19 patients had enriched 4-deoxythreonic acid and depleted 1,5-anhydroglucitol compared to HCs and enriched oxalic acid and depleted phosphoric acid compared to COVID-19-like patients. A combination of d-fructose, citric acid and 2-palmitoyl-glycerol distinguished COVID-19 patients from HCs and COVID-19-like patients, with an area under the curve (AUC) > 0.92 after validation. The combination of 2-hydroxy-3-methylbutyric acid, 3-hydroxybutyric acid, cholesterol, succinic acid, L-ornithine, oleic acid and palmitelaidic acid predicted patients who progressed from mild to severe COVID-19, with an AUC of 0.969. After discharge, nearly one-third of metabolites were recovered in COVID-19 patients.The serum metabolome of COVID-19 patients is distinctive and has important value in investigating pathogenesis, determining a diagnosis, predicting severe cases, and improving treatment.
Clinical and prognostic significance of small paroxysmal nocturnal hemoglobinuria clones in myelodysplastic syndrome and aplastic anemia
Authors: Bruno Fattizzo, Robin Ireland, Alan Dunlop, Deborah Yallop, Shireen Kassam, Joanna Large, Shreyans Gandhi, Petra Muus, Charles Manogaran, Katy Sanchez, Dario Consonni, Wilma Barcellini, Ghulam J. Mufti, Judith C. W. Marsh, Austin G. Kulasekararaj
Journal: Leukemia (2021)

Abstract In this large single-centre study, we report high prevalence (25%) of, small (&lt;10%) and very small (&lt;1%), paroxysmal nocturnal hemoglobinuria (PNH) clones by high-sensitive cytometry among 3085 patients tested. Given PNH association with bone marrow failures, we analyzed 869 myelodysplastic syndromes (MDS) and 531 aplastic anemia (AA) within the cohort. PNH clones were more frequent and larger in AA vs. MDS ( p = 0.04). PNH clone, irrespective of size, was a good predictor of response to immunosuppressive therapy (IST) and to stem cell transplant (HSCT) (in MDS: 84% if PNH+ vs. 44.7% if PNH−, p = 0.01 for IST, and 71% if PNH+ vs. 56.6% if PNH− for HSCT; in AA: 78 vs. 50% for IST, p &lt; 0.0001, and 97 vs. 77%, p = 0.01 for HSCT). PNH positivity had a favorable impact on disease progression (0.6% vs. 4.9% IPSS-progression in MDS, p &lt; 0.005; and 2.1 vs. 6.9% progression to MDS in AA, p = 0.01), leukemic evolution (6.8 vs. 12.7%, p = 0.01 in MDS), and overall survival [73% (95% CI 68–77) vs. 51% (48–54), p &lt; 0.0001], with a relative HR for mortality of 2.37 (95% CI 1.8–3.1; p &lt; 0.0001) in PNH negative cases, both in univariate and multivariable analysis. Our data suggest systematic PNH testing in AA/MDS, as it might allow better prediction/prognostication and consequent clinical/laboratory follow-up timing.
A pilot study of preoperative nivolumab in high-risk nonmetastatic renal cell carcinoma.
Authors: Maria Isabel Carlo, Kyrollis Attalla, Sujata Patil, Samuel J. Murray, Ying-Bei Chen, Ritesh Kotecha, Jeremy C. Durack, Robert J. Motzer, A. Ari Hakimi, Martin H Voss
Journal: Journal of Clinical Oncology (2021)

323 Background: Immunotherapy improves survival in patients with advanced renal cell carcinoma (RCC), but has no established role for perioperative use in patients with localized RCC. Neoadjuvant immunotherapy is a promising strategy in several cancers, and may leverage the primary tumor as antigen source. Methods: We conducted a single institution pilot study of neoadjuvant nivolumab in patients with RCC undergoing nephrectomy with curative intent. Patients were eligible if their risk of metastatic recurrence within the first 12 years was &gt;20% by an established nomogram. After confirmatory biopsy and renal MRI, patients were treated with standard dose nivolumab every 2 weeks for 4 treatments, with a follow-up renal MRI prior to nephrectomy. The primary end points of the study were safety and feasibility defined as being able to complete 3/4 treatments without surgical delay. We evaluated adverse events by CTCAE, surgical safety by Clavien-Dindo classification, and tumor radiographic response by RECIST 1.1. Results: Eighteen (11 men, 7 women; median age 60) were enrolled. All patients had clear cell RCC, median tumor size at baseline was 8.8cm (range 6.4-14.2cm). Median predicted 12-year probability of recurrence was 45% (range 25-71%). All received at least 1 dose of nivolumab; 16/18 patients completed all 4 doses. 17/18 (94%) patients completed at least 3 doses. No patient had notable delay in the timing of their nephrectomy. 4 patients had surgical complications per Clavien-Dindo classification, including 2 with grade 3a chylous ascites after lymphadenectomy. Two patients had nivolumab discontinued for immune-related adverse events, including grade 3 transaminitis and grade 2 arthralgias; a third patient developed grade 4 colitis 4 months after completing nivolumab. All patients had stable disease as the best response prior to surgery. Recurrence-free survival at 2 years was 0.74 (95%CI 0.45-0.90). We analyzed an additional 21 patients with metastatic RCC (20 ccRCC, 1 epithelioid AML) who subsequently had nephrectomy after standard immunotherapy. 15 patients had received ipilimumab+nivolumab, 6 received single-agent PD-1 or PD-L1 inhibitors. 3 (14%) patients achieved a near or complete pathologic response, including a patient with epithelioid AML. Analysis of radiologic and pathologic biomarkers of response are ongoing and will be presented at conference. Conclusions: In this pilot study, there were no new safety signals or delays in surgery with preoperative nivolumab. Neoadjuvant immunotherapy shows preliminary evidence of safety, feasibility and efficacy; biomarker studies may help identify individuals who may have a higher likelihood of response. Clinical trial information: NCT02595918 .
Serum Monocyte-Chemoattractant Protein–1 Could Be an Indicator of Coronary Artery Calcium Score
Authors: Imdat Eroglu, Burcu Çelik Eroglu
Journal: JAMA Cardiology (2021)

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Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease
Authors: Laxminath Tumburu, Shohini Ghosh-Choudhary, Fayaz T. Seifuddin, Emilia A. Barbu, Simon Yang, Maliha M. Ahmad, Lauren H. W. Wilkins, Ilker Tunc, Ishwarya Sivakumar, James S. Nichols, Pradeep K. Dagur, Shutong Yang, Luis E. F. Almeida, Zenaide M. N. Quezado, Christian A. Combs, Eric Lindberg, Christopher K. E. Bleck, Jun Zhu, Arun S. Shet, Jay H. Chung, Mehdi Pirooznia, Swee Lay Thein
Journal: Blood (2021)