tbuckley/cabot-search huggingface dataset:
Performance Analysis of a Novel Hydrophilic-Coated Transradial Guiding Catheter
Authors: A.J.J. IJsselmuiden
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Aim: The transradial approach (TRA) has taken an upswing, however access-site complications still exist. The choice of potentially less traumatic materials may minimize these complications. This article describes the use of a hydrophilic-coated 6F guiding catheter for diagnostic and interventional procedures and upper extremity dysfunction following these procedures. Materials and Methods: This prospective observational study enrolled 217 patients who underwent elective transradial percutaneous coronary intervention (TR-PCI) for stable and unstable angina, or acute coronary syndrome between May 2014 and November 2016. All patients were treated using a 6F hydrophilic-coated guiding catheter (PRIMUM, PendraCare, Wellinq, the Netherlands). Catheter performance was assessed on a five-point scale ranging from very bad to very good. Procedure safety was assessed using the Major cardiac and cerebrovascular events (MACCE) criteria. Results: The average number of guiding catheters used was 1.2 per patient. Overall performance of the catheters was rated Average/Good. Procedural success, defined as TIMI grade 3 flow and successful stent deployment, with a residual diameter stenosis of &lt;25%, was 97.7%. MACCE occurred in 1.5% during the 6-months of follow-up. Conclusion: These data indicate that the use of a hydrophilic-coated guiding catheter to perform percutaneous coronary interventions is safe and effective, with high procedural success and low complication rates. In addition, the short and long-term MACCE outcomes of the PCI were favorable.
Abstract PS6-47: Breast cancer and COVID-19: Impact of active treatment on severe outcomes
Authors: Karine Tawagi, Jeff Burton, Michael Lunski, Diana Maslov, John Cole
Journal: Cancer Research (2021)

Abstract Background: Several reports have observed that cancer patients who recently underwent chemotherapy or surgery had a higher risk of severe events compared with patients without cancer. Limited data is available on outcomes in specific cancer types, as well as the impact of non-cytotoxic systemic treatment, such as targeted therapy and hormonal therapy on severe outcomes. We aim to identify whether active treatment impacts severe outcomes (rate of hospitalization, ICU admission, intubation, and death) in breast cancer patients. Methods: We conducted a multicenter study in the state of Louisiana, throughout the Ochsner Health System, in both tertiary and non-tertiary centers. Patients must carry a diagnosis of breast cancer, and have a completed SARS-CoV-2 test between March 1st and April 30th, 2020. Chi-squared and Fisher’s exact tests were performed to compare the proportion of patients experiencing severe outcomes between treatment groups. Results: As of April 30, 2020, a total of 70 patients with breast cancer who had a positive SARS-COV-2 test were identified. Median age 64.5, median BMI 30.8, 62.9% (n=44) black, 27.1% (n=19) current/former smokers, HTN (n=52) and DM2 (n=22) were the most common comorbidities, and 12.9% (n=9) of patients had stage IV disease. Of these patients, 58.6% (n=41) were on hormonal treatment, and another 12.9% (n=9) were receiving other forms of systemic therapy (cytotoxic chemotherapy or targeted therapy). In terms of severe outcomes, 32.9% (n=23) of patients required hospitalization, 8.6% (n=6) required ICU admission with 7.1% (n=5) patients requiring intubation, 11.4% (n=8) of patients died. There was not a statistical difference in rate of severe outcomes (rate of hospitalization, ICU admission, intubation, and death) among breast cancer patients receiving active treatment (chemotherapy, targeted therapy, or hormonal therapy) vs those receiving no active treatment. There was also no difference in terms of severe outcomes by race. Conclusion: With an ongoing global COVID-19 pandemic, it is important to identify how the treatment and management of cancer impacts COVID-19 outcomes. This small cohort does not identify active treatment as a risk factor for increased rate of severe outcomes in patients with breast cancer. Further analyses describing impact of specific hormonal and chemotherapy regimens on risk of hospitalization and death will be completed by time of presentation. Citation Format: Karine Tawagi, Jeff Burton, Michael Lunski, Diana Maslov, John Cole. Breast cancer and COVID-19: Impact of active treatment on severe outcomes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-47.
Abstract 10362: Chronic Therapy With Sacubitril/Valsartan Normalizes Myocardial Expression of Vascular Endothelial, Hepatocyte and Fibroblast Growth Factors in Dogs With Experimentally-Induced Cardiorenal Syndrome
Authors: Hani N Sabbah, Ramesh C Gupta, Vinita Singh-Gupta, Zhang Kefei
Journal: Circulation (2018)

Introduction: The failing left ventricular (LV) myocardium manifests a host of abnormalities that include down-regulation of multi-functional growth factors that regulate cellular growth, fibrosis ...
Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia
Authors: Daniele Caracciolo, Caterina Riillo, Andrea Ballerini, Giuseppe Gaipa, Ludovic Lhermitte, Marco Rossi, Cirino Botta, Eugénie Duroyon, Katia Grillone, Maria Eugenia Gallo Cantafio, Chiara Buracchi, Greta Alampi, Alessandro Gulino, Beatrice Belmonte, Francesco Conforti, Gaetanina Golino, Giada Juli, Emanuela Altomare, Nicoletta Polerà, Francesca Scionti, Mariamena Arbitrio, Michelangelo Iannone, Massimo Martino, Pierpaolo Correale, Gabriella Talarico, Andrea Ghelli Luserna di Rorà, Anna Ferrari, Daniela Concolino, Simona Sestito, Licia Pensabene, Antonio Giordano, Markus Hildinger, Maria Teresa Di Martino, Giovanni Martinelli, Claudio Tripodo, Vahid Asnafi, Andrea Biondi, Pierosandro Tagliaferri, Pierfrancesco Tassone
Journal: Journal for ImmunoTherapy of Cancer (2021)

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a poor cure rate for relapsed/resistant patients. Due to the lack of T-cell restricted targetable antigens, effective immune-therapeutics are not presently available and the treatment of chemo-refractory T-ALL is still an unmet clinical need. To develop novel immune-therapy for T-ALL, we generated an afucosylated monoclonal antibody (mAb) (ahuUMG1) and two different bispecific T-cell engagers (BTCEs) against UMG1, a unique CD43-epitope highly and selectively expressed by T-ALL cells from pediatric and adult patients.
Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer
Authors: Dristhi Ragoonanan, Sajad J. Khazal, Hisham Abdel-Azim, David McCall, Branko Cuglievan, Francesco Paolo Tambaro, Ali Haider Ahmad, Courtney M. Rowan, Cristina Gutierrez, Keri Schadler, Shulin Li, Matteo Di Nardo, Linda Chi, Alison M. Gulbis, Basirat Shoberu, Maria E. Mireles, Jennifer McArthur, Neena Kapoor, Jeffrey Miller, Julie C. Fitzgerald, Priti Tewari, Demetrios Petropoulos, Jonathan B. Gill, Christine N. Duncan, Leslie E. Lehmann, Sangeeta Hingorani, Joseph R. Angelo, Rita D. Swinford, Marie E. Steiner, Fiorela N. Hernandez Tejada, Paul L. Martin, Jeffery Auletta, Sung Won Choi, Rajinder Bajwa, Natalie Dailey Garnes, Partow Kebriaei, Katayoun Rezvani, William G. Wierda, Sattva S. Neelapu, Elizabeth J. Shpall, Selim Corbacioglu, Kris M. Mahadeo
Journal: Nature Reviews Clinical Oncology (2021)
Cleansing and separating: From modern agriculture and genocide to post-separation era
Authors: Michal Bilewicz, Aleksandra Bilewicz
Journal: Behavioral and Brain Sciences (2021)

Abstract We propose that the metaphor of cleansing was a by-product of modernization processes. Based on cultural and historical evidence, we claim that the activation of cleansing metaphor triggered positive associations in times when separation was a positively regarded element of human culture and agriculture, but it should not exert the same effect in times when separation became culturally anachronistic.
SARS-CoV-2 nsp12 attenuates type I interferon production by inhibiting IRF3 nuclear translocation
Authors: Wenjing Wang, Zhuo Zhou, Xia Xiao, Zhongqin Tian, Xiaojing Dong, Conghui Wang, Li Li, Lili Ren, Xiaobo Lei, Zichun Xiang, Jianwei Wang
Journal: Cellular and Molecular Immunology (2021)

Abstract SARS-CoV-2 is the pathogenic agent of COVID-19, which has evolved into a global pandemic. Compared with some other respiratory RNA viruses, SARS-CoV-2 is a poor inducer of type I interferon (IFN). Here, we report that SARS-CoV-2 nsp12, the viral RNA-dependent RNA polymerase (RdRp), suppresses host antiviral responses. SARS-CoV-2 nsp12 attenuated Sendai virus (SeV)- or poly(I:C)-induced IFN-β promoter activation in a dose-dependent manner. It also inhibited IFN promoter activation triggered by RIG-I, MDA5, MAVS, and IRF3 overexpression. Nsp12 did not impair IRF3 phosphorylation but suppressed the nuclear translocation of IRF3. Mutational analyses suggested that this suppression was not dependent on the polymerase activity of nsp12. Given these findings, our study reveals that SARS-CoV-2 RdRp can antagonize host antiviral innate immunity and thus provides insights into viral pathogenesis.
Sitagliptin (MK-0431), a Selective Dipeptidyl-Peptidase-IV (DPP-IV) Inhibitor, does not affect the Pharmacokinetics of Simvastatin in Humans. 2005; 79: P48
Authors: A Bergman, J Cote, A Maes, J Zhao, B Roadcap, L.-M. Sun, R Valesky, A Yang, Bart Keymeulen, J. Wagner, G Herman
Journal: Pharmacology & Therapeutics (2005)
Abstract PD12-11: Patient-reported outcomes from the Phase III IMpassion031 trial of neoadjuvant atezolizumab + chemotherapy in early triple-negative breast cancer
Authors: Elizabeth Mittendorf, Nadia Harbeck, Hong (Amy) Zhang, Shigehira Saji, Kyung Hae Jung, Sheetal Patel, Shilpen Patel, Anh Nguyen Duc, Mario Liste-Hermoso, Stephen Y Chui, Carlos H Barrios
Journal: Cancer Research (2021)

Abstract Background: In the IMpassion031 study (NCT03197935) of patients (N = 333) with invasive stage II or III early triple-negative breast cancer (eTNBC), neoadjuvant treatment with atezolizumab vs placebo, each combined with nab-paclitaxel followed by doxorubicin + cyclophosphamide, significantly improved pathologic complete response in the intent-to-treat population. Patient-reported outcomes (PROs) were collected to document patient perspectives on overall treatment burden and clinical benefit of atezolizumab + chemotherapy for neoadjuvant treatment of eTNBC. Methods: Patients received either atezolizumab 840 mg or placebo every 2 weeks (q2w) with nab-paclitaxel 125 mg/m2 every week for 12 weeks followed by atezolizumab 840 mg or placebo q2w with doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 q2w for 4 cycles. After surgery, patients in the atezolizumab arm were unblinded and continued to receive atezolizumab 1200 mg every 3 weeks for 11 doses, while patients in the control arm did not receive any study treatment. Patients completed the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) and single-item GP5 from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline and day 1 of each cycle of neoadjuvant and adjuvant treatment, at end of treatment and during follow-up every 3 months during year 1, every 6 months during years 2-3, and then annually. Mean and mean change from baseline scores (with changes ≥ 10 considered clinically meaningful) in function (role and physical) and global health status/health-related quality of life (GHS/HRQoL) were predefined secondary endpoints. Mean and mean change from baseline scores in disease and treatment-related symptoms, as well as an assessment of overall side-effect bother, were exploratory endpoints. Expected results: The PROs will be compared between the atezolizumab and placebo arms to assess overall treatment burden and the effect of adding atezolizumab to neoadjuvant chemotherapy for the treatment of eTNBC. Citation Format: Elizabeth Mittendorf, Nadia Harbeck, Hong (Amy) Zhang, Shigehira Saji, Kyung Hae Jung, Sheetal Patel, Shilpen Patel, Anh Nguyen Duc, Mario Liste-Hermoso, Stephen Y Chui, Carlos H Barrios. Patient-reported outcomes from the Phase III IMpassion031 trial of neoadjuvant atezolizumab + chemotherapy in early triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-11.
Temporal Trends in Prognosis of Patients with Acute Coronary Syndrome Complicated by Ventricular Tachyarrhythmia
Authors: Ella Yahud
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Objectives: To evaluate clinical characteristics and prognosis of patients presented with ventricular tachyarrhythmia (VTA) during the course of acute coronary syndrome (ACS) and to analyze it according to period of presentation. Background: VTA is an infrequent yet serious complication of ACS. There is limited data regarding the incidence and prognostic implications of VTA in the last decade as compared with the previous decade. Methods: We evaluated clinical characteristics, major adverse cardiovascular events, short and long- term mortality of patients hospitalized with ACS who were enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS) during the years 2000-2016. Patients were classified into three groups: no VTA, early VTA (≤48h of onset) and late VTA (&gt;48h of onset). Data were analyzed according to decades of presentation (current decade vs. previous decade). Results: The study population comprised 15,200 patients. VTA occurred in 487 (3.2%) of patients. Early VTA presented in 373/487 (77%) patients and late VTA in 114/487 (23%) patients. VTA’s, occurring in ACS patients were associated with increased risk of in-hospital, 30-days, 1-year and 5-year mortality rates during both early and late periods in compared with no VTA. Moreover, late VTA was associated with the highest mortality rate with up to 65% in 5-year follow up (p&lt;0.001). Nevertheless, late VTA was associated with lower mortality rate in the current decade (2008-2016) compared with last decade (2000-2006). Conclusions: Any VTA following ACS was associated with high short and long-term mortality rate. Howevr, over the past decade there has been a significant improvement in survival rates, especially in patients with late VTA. This may be attributed to early and invasive reperfusion therapy, implantable cardioverter defibrillator implantation and better medical treatment.
Reply to: Axel Heidenreich. Still Unanswered: The Role of Extended Pelvic Lymphadenectomy in Improving Oncological Outcomes in Prostate Cancer. Eur Urol 2021;79:605–6
Authors: Jean F.P. Lestingi, Giuliano B. Guglielmetti, Quoc-Dien Trinh, Rafael F. Coelho, Jose Pontes, Diogo A. Bastos, Mauricio D. Cordeiro, Alvaro S. Sarkis, Sheila F. Faraj, Anuar I. Mitre, Miguel Srougi, William C. Nahas
Journal: European Urology (2021)
Lewis Wolpert: developmental biologist who raised the public profile of mental illness
Authors: John Illman
Journal: BMJ (2021)

Photo credit: Shutterstock

The developmental biologist Lewis Wolpert was a polymath with forthright views on everything from depression and religion to old age and philosophy. His highly acclaimed and much reprinted book Malignant Sadness (1999), and the BBC2 series A Living Hell (1999), encouraged other celebrated people who were similarly afflicted to “come out” and raise the public profile of mental illness. Disarmingly frank and honest, Wolpert wrote and spoke about his exploration of depression and his experience of it.

His candour even went so far as to tell how his wife, the Australian writer Jill Neville, reacted to his suicidal feelings. Fearing for his career if the truth came out, she told friends and colleagues that he had been exhausted by a minor heart condition. Wolpert had no such fears. After being complimented for being “brave” in speaking out, he realised how much stigma was still associated with depression. But, he recalled, “It was quite easy for me to write about because I had a secure academic position and nothing to lose.”

There was, he said, no explicable reason why he should have suffered so. He was a UCL professor, healthy, and happily married. But he became suicidal and spent …
HIF2α is a direct regulator of neutrophil motility
Authors: Sundary Sormendi, Mathieu Deygas, Anupam Sinha, Mathilde Bernard, Anja Krüger, Ioannis Kourtzelis, Gregoire Le Lay, Pablo J. Sáez, Michael Gerlach, Kristin Franke, Ana Meneses, Martin Kräter, Alessandra Palladini, Jochen Guck, Ünal Coskun, Triantafyllos Chavakis, Pablo Vargas, Ben Wielockx
Journal: Blood (2021)
Flu vaccination: Lansley reforms caused London to fall behind in uptake, report finds
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The Health and Social Care Act 2012 led to London falling behind in flu vaccination rates, a report has concluded.

The centralisation of vaccine coordination that stemmed from Andrew Lansley’s reforms disproportionately affected London, said the report from the Royal Society for Public Health.1

The reforms led to just one person being accountable for flu vaccination across the whole of London, covering 2.2 million eligible patients and 2186 general practices. After the 2012 act the ratio of patients to each individual immunisation lead increased by 36 times in London, compared with seven times in …
Integrating genome-wide CRISPR immune screen with multi-omic clinical data reveals distinct classes of tumor intrinsic immune regulators
Authors: Jiakai Hou, Yunfei Wang, Leilei Shi, Yuan Chen, Chunyu Xu, Arash Saeedi, Ke Pan, Ritu Bohat, Nicholas A. Egan, Jodi A. McKenzie, Rina M. Mbofung, Leila J. Williams, Zhenhuang Yang, Ming Sun, Xiaofang Liang, Jordi Rodon Ahnert, Navin Varadarajan, Cassian Yee, Yiwen Chen, Patrick Hwu, Weiyi Peng
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Despite approval of immunotherapy for a wide range of cancers, the majority of patients fail to respond to immunotherapy or relapse following initial response. These failures may be attributed to immunosuppressive mechanisms co-opted by tumor cells. However, it is challenging to use conventional methods to systematically evaluate the potential of tumor intrinsic factors to act as immune regulators in patients with cancer. Methods To identify immunosuppressive mechanisms in non-responders to cancer immunotherapy in an unbiased manner, we performed genome-wide CRISPR immune screens and integrated our results with multi-omics clinical data to evaluate the role of tumor intrinsic factors in regulating two rate-limiting steps of cancer immunotherapy, namely, T cell tumor infiltration and T cell-mediated tumor killing. Results Our studies revealed two distinct types of immune resistance regulators and demonstrated their potential as therapeutic targets to improve the efficacy of immunotherapy. Among them, PRMT1 and RIPK1 were identified as a dual immune resistance regulator and a cytotoxicity resistance regulator, respectively. Although the magnitude varied between different types of immunotherapy, genetically targeting PRMT1 and RIPK1 sensitized tumors to T-cell killing and anti-PD-1/OX40 treatment. Interestingly, a RIPK1-specific inhibitor enhanced the antitumor activity of T cell-based and anti-OX40 therapy, despite limited impact on T cell tumor infiltration. Conclusions Collectively, the data provide a rich resource of novel targets for rational immuno-oncology combinations.
G9a Inhibition Enhances Checkpoint Inhibitor Blockade Response in Melanoma
Authors: Gregory M. Kelly, Fares Al-Ejeh, Robert McCuaig, Francesco Casciello, Nabilah Ahmad Kamal, Blake Ferguson, Antonia L. Pritchard, Sayed Ali, Ines P. Silva, James S. Wilmott, Georgina V. Long, Richard A. Scolyer, Sudha Rao, Nicholas K. Hayward, Frank Gannon, Jason S. Lee
Journal: Clinical Cancer Research (2021)

Abstract Purpose: G9a histone methyltransferase exerts oncogenic effects in several tumor types and its inhibition promotes anticancer effects. However, the impact on checkpoint inhibitor blockade response and the utility of G9a or its target genes as a biomarker is poorly studied. We aimed to examine whether G9a inhibition can augment the efficacy of checkpoint inhibitor blockade and whether LC3B, a G9a target gene, can predict treatment response. Experimental Design: Clinical potential of LC3B as a biomarker of checkpoint inhibitor blockade was assessed using patient samples including tumor biopsies and circulating tumor cells from liquid biopsies. Efficacy of G9a inhibition to enhance checkpoint inhibitor blockade was examined using a mouse model. Results: Patients with melanoma who responded to checkpoint inhibitor blockade were associated with not only a higher level of tumor LC3B but also a higher proportion of cells expressing LC3B. A higher expression of MAP1LC3B or LC3B protein was associated with longer survival and lower incidence of acquired resistance to checkpoint inhibitor blockade, suggesting LC3B as a potential predictive biomarker. We demonstrate that G9a histone methyltransferase inhibition is able to not only robustly induce LC3B level to augment the efficacy of checkpoint inhibitor blockade, but also induces melanoma cell death. Conclusions: Checkpoint inhibitor blockade response is limited to a subset of the patient population. These results have implications for the development of LC3B as a predictive biomarker of checkpoint inhibitor blockade to guide patient selection, as well as G9a inhibition as a strategy to extend the proportion of patients responding to immunotherapy.