tbuckley/cabot-search huggingface dataset:
Abstract 302: NeuroCardiac Comprehensive Care Clinic Seeks to Define and Detect Neurological, Psychiatric, and Functional Sequelae in Cardiac Arrest Survivors
Authors: Sachin Agarwal, Alex Presciutti, Deepti Anbarasan, Linda Golding, Marykay Pavol
Journal: Circulation (2018)

Introduction: Despite improved survivability, cardiac arrest (CA) survivors face significant “extracardiac” (i.e. functional, cognitive and psychosocial) sequelae. More so, survivors and their caregivers are seemingly unaware that they will be confronted with these issues post-discharge. As a response, we have created a multidisciplinary, follow-up clinic to provide comprehensive and well-coordinated care to CA survivors. The team includes a neurointensivist, neuropsychologist, neuropsychiatrist and a chaplain. Hypothesis: CA survivors attending a follow-up clinic will have improved outcomes compared to historical controls. Methods: Fisher’s exact and Wilcoxon Rank-sum tests were used to assess differences in 1-year outcomes between survivors who had at least one follow-up visit in the NeuroCardiac clinic (2/2017-1/2018), with historical controls (9/2015 - 1/2017) who had no clinic visits. Results: Clinic patients (n= 34; median visit per patient=2), were slightly younger (49 vs 57 years, p=0.03) than historic controls (n=47), but otherwise there were no significant differences in demographic, psychosocial or functional status at hospital discharge. At 1-year, clinic patients, compared to historic controls, had significantly greater independence on the Lawton Physical Self-Maintenance Scale (mean score 7.6 vs 8.9, p=0.03) and Instrumental Activities of Daily Living scale (4.9 vs 8.8, p =.01). In clinic patients, there was a trend towards return to work (38.2% vs 23.4%), having a less negative impact on their marital status (5.9% vs 21.3%) and reduced complaints of sleep issues (29% vs 52%). Clinic patients had lower rates of depression symptoms on the Center for Epidemiological Studies-Depression scale (9.8 vs 13.4), were less fearful about the possibility of arrest recurrence (23.5% vs 31.9%), had more positive recovery perceptions (55.9% vs 38.3%), and had higher self-reported overall health ratings on a 100-point scale (84.7 vs 75.4) at one year. Conclusions: We have taken an important step in early detection of extracardiac symptoms in a systematic manner after CA. This paradigm shift could potentially be utilized to develop and implement novel interventions responsible for improving clinical outcomes and quality of life.
Abstract 10116: Association Between Biomechanical Stresses of Atherosclerotic Carotid Plaques and Subsequent Ischaemic Cerebrovascular Events
Authors: Umar Sadat, Zhongzhao Teng, Jonathan H Gillard
Journal: Circulation (2010)

Background: High resolution magnetic resonance (MR) imaging has been successfuly used to assess morphology of carotid atherosclerotic plaques. It also provides excellent information about plaque ge...
Transparency and accountability in the negotiation of the US-Mexico-Canada trade agreement: the case of pharmaceuticals
Authors: Anna S Y Wong, Clarke B Cole, Jillian C Kohler
Journal: The Lancet Global Health (2021)

BackgroundTransparency and accountability are essential components at all stages of the trade negotiation process. This study reports on the findings of an evaluation of the United States' public consultation process during the re-negotiation of the North American Free Trade Agreement (NAFTA)/United States-Mexico-Canada Agreement (USMCA) with respect to medicines and the pharmaceutical sector.MethodsA desk review was conducted to map the US negotiation rounds of the USMCA. Then, opportunities for the public to receive information and provide feedback about the proposed agreement provisions were identified. Finally, the written comments submitted by stakeholders during this public consultation process to the Federal Register (Regulations.gov) were queried and analysed using qualitative data analysis software NVivo for language related to pharmaceuticals and medicine.FindingsThe public consultation process occurred before the start of official negotiations. It was overseen by the Office of the US Trade Representative (USTR) and included both written comments and oral testimony about US negotiation objectives. There were no further official opportunities for the public to engage with the negotiation process. Of the 1458 comments publicly available through the Federal Register, 75 specifically discussed issues related to pharmaceuticals for human use. More than 50% of submissions received from members or affiliates of the pharmaceutical industry advocated for strengthened pharmaceutical intellectual property rights, greater regulatory data protection, or both. Nearly all submissions from non-industry groups indicated that access to, or the affordability of, medicines was a priority issue area in the renegotiated agreement. Most submissions that directly discussed transparency and accountability were authored by industry groups and emphasised the importance of predictability and transparency in the areas of pharmaceutical intellectual property, regulatory affairs, pricing, and reimbursement to facilitate greater innovation.InterpretationUSMCA increased regulatory data protection for innovator drugs, increased the period of regulatory exclusivity for biologics, and granted patent term restoration provisions for regulatory delays, undermining public access to medicines. Although industry comments only constitute 26% of the comments submitted during the US public consultation period related to pharmaceuticals, they reflect the dominant position adopted in the USMCA.FundingConnaught Fund Global Health Challenge Award.
Characterization of DLBCL with a PMBL gene expression signature
Authors: Gerben Duns, Elena Viganò, Daisuke Ennishi, Clementine Sarkozy, Stacy S. Hung, Elizabeth Chavez, Katsuyoshi Takata, Christopher Rushton, Aixiang Jiang, Susana Ben-Neriah, Bruce W. Woolcock, Graham W. Slack, Eric D. Hsi, Jeffrey W. Craig, Laura K. Hilton, Sohrab P. Shah, Pedro Farinha, Anja Mottok, Randy D. Gascoyne, Ryan D. Morin, Kerry J. Savage, David W. Scott, Christian Steidl
Journal: Blood (2021)
Long-term survival outcomes of cytoreductive nephrectomy combined with targeted therapy for metastatic renal cell carcinoma: A systematic review and individual patient data meta-analysis.
Authors: Stepan M. Esagian, Ioannis A. Ziogas, Dimitrios Kosmidis, Mohammad D. Hossain, Nizar M. Tannir, Pavlos Msaouel
Journal: Journal of Clinical Oncology (2021)

317 Background: The role of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy agents remains controversial. We used reconstructed individual patient data (IPD) to compare the long-term survival outcomes of CN combined with targeted therapy vs. targeted therapy alone for mRCC. Methods: We performed a systematic review of the literature using the MEDLINE, Scopus, and Cochrane Library databases (end-of-search date: July 21, 2020). We reconstructed the Kaplan-Meier curves and subsequently recuperated IPD for overall (OS), progression-free (PFS) and cancer-specific survival (CSS) from individual studies. We performed one-stage random-effects frequentist and Bayesian meta-analyses of OS, PFS, and CSS using parametric and non-parametric estimates. We also performed a subgroup analysis focusing on upfront CN and excluding patients with deferred CN. The risk of bias was assessed using the ROBINS-I and RoB2 tools. Results: Fifteen studies fulfilling our inclusion criteria were identified, including fourteen retrospective cohort studies and one randomized controlled trial. No studies were found to be at critical risk of bias. A total of 3,990 patients were included, with 2,234 in the CN group and 1,756 in the non-CN group. Our frequentist meta-analysis showed superior OS (HR = 0.58, 95% CI: 0.54-0.62, p&lt;0.0001) and CSS (HR = 0.63, 95% CI: 0.53-0.75, p &lt; 0.0001) in favor of CN. No clinically meaningful differences were observed in the PFS between the two groups (HR = 0.90, 95% CI: 0.80-1.02, p=0.09). The OS benefit was also observed in the upfront CN subgroup (HR = 0.70, 95% CI 0.63-0.78, p&lt;0.001). Similar results were obtained with non-parametric frequentist and Bayesian approaches (Table). Conclusions: The combination of CN and targeted therapy for mRCC is associated with superior long-term survival outcomes compared with targeted therapy alone. Careful patient selection based on prognostic factors is required to achieve optimal outcomes. [Table: see text]
COVID-19 disaster response: an emergency food and supply distribution programme in Bahía de Caráquez, Ecuador
Authors: Madison Searles, Andrew Jeffery, Yaa Takyiwaa, Breana Wonsey, David Cedeño, Christina Lupone, Avriel Diaz
Journal: The Lancet Global Health (2021)

BackgroundThe COVID-19 pandemic has further challenged the world's most vulnerable populations' access to adequate food. The UN World Food Program estimates that COVID-19 will increase worldwide food insecurity from 135 million to 265 million people by 2021. In March, 2020, Walking Palms Global Health (WPGH) initiated their More than Food Emergency Relief Program in Bahía de Caráquez, Ecuador, working with local government to deliver food and supplies to at-risk households. We aim to assess how WPGH's response affected households early in the 2020 pandemic.MethodsBetween March and July, 2020, rations were delivered to 225 families in rural, urban, and peri-urban communities within the city of Bahia de Caráquez located in the province of Manabí on Ecuador's west coast. These specific communities face frequent piped water disruptions, power outages, and mosquito-transmitted diseases such as dengue are endemic. In June, 2020, WPGH administered evaluations in the urban and rural communities, which included the World Food Program Food Confidence Score to address food consumption, food accessibility stress, and presence of chronic diseases.FindingsEvaluations were conducted in 21 of 45 urban households (47%) and 45 of 50 rural households (90%). Overall, 66 households (69%) completed surveys and 29 (31%) opted out. The association between household income before COVID-19 and food insecurity was significant (p=0·04). Before the first programme delivery, 59 participants (92%) worried that their household would experience food insecurity and most often felt nervous or stressed about possible food insecurity (n=55 [85%]). Insufficient access to food led to 55 respondents (85%) skipping meals. Food confidence scores remained stable over the pandemic's most challenging period (Food confidence score=37·68% before deliveries and 38·11% during deliveries). Respondents (n=61 [95%]) reported that boxes allowed them to prepare enjoyable and culturally appropriate meals. The most common combination of meals cooked with box items was rice and beans, stews, corviche, empanadas, and plantains with 98% of participants finding every box item useful. There was no relation between food insecurity and number of children (p=0·26) or number of people in households (p=1·00). There was no significant association between chronic disease and pre-COVID-19 household income (p=0·24) or respondents' food security (p=0·82).InterpretationIn communities that had high food insecurity before the pandemic, WPGH's response allowed households to maintain overall food consumption throughout the most challenging lockdown period. WPGH is currently working to innovatively and sustainably increase food security in the communities where they work. Limitations include programme administration relying on donor participation for financial support.FundingNone.
Reply to: Kow CS et al. Are severe asthma patients at higher risk of developing severe outcomes from COVID‐19?
Authors: Enrico Heffler, Aikaterini Detoraki, Marco Contoli, Alberto Papi, Giovanni Paoletti, Giacomo Malipiero, Luisa Brussino, Claudia Crimi, Daniela Morrone, Marianna Padovani, Giuseppe Guida, Alberto Giovanni Gerli, Stefano Centanni, Gianenrico Senna, Pierluigi Paggiaro, Francesco Blasi, Giorgio Walter Canonica
Journal: Allergy (2021)

Enrico Heffler reports participation to advisory boards and personal fees from AstraZeneca, Sanofi, GSK, Novartis, Circassia, Nestlè Purina, Boheringer Ingelheim and Valeas, outside the submitted work. Marco Contoli reports grants from Chiesi, and University of Ferrara—Italy, and personal fees from Chiesi, AstraZeneca, Boehringer Ingelheim, Alk-Abello, GlaxoSmithKline, Novartis and Zambon, outside the submitted work. Alberto Papi reports grants, grants, personal fees and non-financial support from AstraZeneca and Menarini; grants, personal fees, non-financial support and other from Boehringer Ingelheim, Chiesi Farmaceutici and TEVA; personal fees, non-financial support and other from GlaxoSmithKline, Mundipharma, Zambon, Novartis and Sanofi/Regeneron; personal fees from Roche and Edmond Pharma; and grants from Fondazione Maugeri and Fondazione Chiesi, outside the submitted work. Claudia Crimi reports personal fees from Menarini. Stefano Centanni reports personal fees from GlaxoSmithKline, Novartis, Menarini SpA, and Guidotti-Malesci, and grants and personal fees from Chiesi SpA, AstraZeneca, Valeas and Boehringer Ingelheim, outside the submitted work. Pierluigi Paggiaro reports grants and personal fees from AstraZeneca, Chiesi, Novartis and Sanofi, and personal fees from GlaxoSmithKline, Guidotti, and Mundipharma, outside the submitted work. Francesco Blasi reports grants and personal fees from AstraZeneca, Chiesi, GSK, Pfizer and Insmed; grants from Bayer; and personal fees from Guidotti, Grifols, Menarini, Mundipharma, Novartis and Zambon, outside the submitted work. Giorgio Walter Canonica reports grants as well as lecture or advisory board fees from: A. Menarini, Alk-Abello, Allergy Therapeutics, AstraZeneca, Boehringer-Ingelheim, Chiesi Farmaceutici, Genentech, Guidotti-Malesci, GlaxoSmithKline, Hal Allergy, Mylan, Merck, Mundipharma, Novartis, Regeneron, Sanofi-Aventis, Sanofi-Genzyme, Stallergenes Greer, UCB pharma, Uriach Pharma, Valeas and Vibro Pharma. Giovanni Paoletti, Aikaterini Detoraki, Giacomo Malipiero, Luisa Brussino, Daniela Morrone, Marianna Padovani, Giuseppe Guida, Alberto Giovanni Gerli and Gianenrico Senna do not have any conflict of interest to report.
Correspondence on ‘Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry’
Authors: Ben Mulhearn
Journal: Annals of the Rheumatic Diseases (2021)

I read with great interest the recent work from the COVID-19 European League Against Rheumatism registry authored by Strangfeld et al and the COVID-19 Global Rheumatology Alliance1 describing the risk factors for COVID-19 mortality in patients with rheumatic diseases.

It should perhaps not be surprising that high disease activity in rheumatic diseases is associated with mortality from COVID-19. In rheumatoid arthritis, high disease activity has been shown to be an independent risk factor for severe infection, with a 30% increase in relative risk for every 0.5-unit increase in the 28-joint Disease Activity Score (DAS28).2 The same authors found no association between either biologic or glucocorticoid use and severe infections. The linear relationship between serious infection …
Interleukin-6 produced by enteric neurons regulates the number and phenotype of microbe-responsive regulatory T cells in the gut
Authors: Yiqing Yan, Deepshika Ramanan, Milena Rozenberg, Kelly McGovern, Daniella Rastelli, Brinda Vijaykumar, Omar Yaghi, Tiphaine Voisin, Munir Mosaheb, Isaac Chiu, Shalev Itzkovitz, Meenakshi Rao, Diane Mathis, Christophe Benoist
Journal: Immunity (2021)
Enhanced brain delivery and therapeutic activity of trastuzumab after blood-brain barrier opening by NEO100 in mouse models of brain-metastatic breast cancer
Authors: Weijun Wang, Haiping He, Nagore I Marín-Ramos, Shan Zeng, Steven D Swenson, Hee-Yeon Cho, Jie Fu, Paul M Beringer, Josh Neman, Ligang Chen, Axel H Schönthal, Thomas C Chen
Journal: Neuro-Oncology (2021)

Abstract Background The antitumor efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapies, such as humanized monoclonal antibody trastuzumab (Herceptin®, Roche), in patients with breast-to-brain cancer metastasis is hindered by the low permeability of the blood-brain barrier (BBB). NEO100 is a high-purity version of the natural monoterpene perillyl alcohol, produced under current good manufacturing practice (cGMP) regulations, that was shown previously to reversibly open the BBB in rodent models. Here we investigated whether NEO100 could enable brain entry of trastuzumab to achieve greater therapeutic activity. Methods An in vitro BBB, consisting of human astrocytes and brain endothelial cells, was used to determine trastuzumab penetration in the presence or absence of NEO100. For in vivo studies, we administered intravenous (IV) trastuzumab or the trastuzumab-drug conjugate ado-trastuzumab emtansine (T-DM1; Kadcyla®, Roche), to mouse models harboring intracranial HER2+ breast cancer, with or without BBB opening via IA NEO100. Brain and tumor tissues were examined for the presence of trastuzumab and infiltration of immune cells. Therapeutic impact was evaluated based on overall survival. Results NEO100 greatly increased trastuzumab penetration across an in vitro BBB. In vivo, IA NEO100-mediated BBB opening resulted in brain tumor-selective accumulation of trastuzumab, without detectable presence in normal brain tissue, along with increased presence of immune cell populations. IV delivery of trastuzumab or T-DM1 achieved significantly greater overall survival of tumor-bearing mice when combined with IA NEO100. Conclusion IA NEO100 facilitates brain tumor entry of trastuzumab and T-DM1 and significantly enhances their therapeutic efficacy, along with increased antibody-dependent immune cell recruitment.
Family history and pathogenic/likely pathogenic germline variants in prostate cancer patients.
Authors: Rachel Sabol, Elisa Marie Ledet, Ellen Jaeger, Marcus W. Moses, Brian E. Lewis, Jodi Lyn Layton, Pedro C. Barata, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2021)

143 Background: Recent literature highlights the importance of germline genetic testing in prostate cancer (PCa) patients. Surprisingly, a literature review indicates that family history records are incomplete in published studies. Methods: Prospective and complete family history data were gathered from 496 men in a single institution with a personal history of PCa who underwent germline genetic testing using a panel of at least 79 genes (Invitae testing) from 2016-2020. Comprehensive FH were obtained in all PCa patients in this database and analysis of prevalent FH was assessed at the time of sample collection. Age, race, metastastes at any time, and Gleason score were also ascertained. MUTYH heterozygotes were not considered pathogenic. Results: Pathogenic/likely pathogenic variants (PV/LPVs) were not associated with age at diagnosis, race, or presence of metastasis. Men with Gleason scores 8-10 at time of diagnosis were more likely to have PV/LPV ( P= 0.004). One or more first degree relatives (FDR) with any cancer with was not predictive for germline PV/LPVs for men with PCa ( P= 0.96). Analysis of patients with one or more FDR with breast, prostate, ovarian, or pancreatic cancer revealed that only FDR with breast cancer ( P = 0.028) or ovarian cancer ( P = 0.015) was predictive for PV/LPVs. Though one or more FDR with prostate cancer did not predict a PV/LPV in the overall panel, further analysis indicate that a history of a FDR with PCa was predictive for PV/LPV in a DNA damage repair (DDR) gene ( P= 0.044). Conclusions: In men with a personal history of PCa, germline PV/LPVs were associated with a FDR with breast or ovarian cancer. A FDR with PCa was predictive for PV/LPV in DDR genes. These data emphasize the contribution of FH to germline genetic testing results in a cohort with complete ascertainment of cancer in first degree relatives.
Outcomes and prognostic factors in metastatic renal cell carcinoma patients with brain metastases.
Authors: İzzet Dogan, Ayca Iribas, Nail Paksoy, Meltem Ekenel, Sezai Vatansever, Mert Basaran
Journal: Journal of Clinical Oncology (2021)

289 Background: The study aimed to evaluate the outcomes and prognostic factors in patients with brain metastatic renal cell carcinoma (bmRCC). Methods: The data of 322 patients with renal cell carcinoma, between 2012 and 2020, were retrospectively reviewed. The clinicopathological features and treatments of the patients with bmRCC were recorded. Overall survival (OS) and prognostic factors were evaluated with Kaplan-Meier analysis and Cox-regression analysis. Results: Forty (12.4%) of the patients had bmRCC. The median follow-up period was 7.3 months (range, 0.2-55.5). The male/female ratio was 2.3, and the median age at diagnosis was 62 years (range, 25-84). Seventeen (42.5%) of the patients were de-novo metastatic, and nine (22.5%) of the patients had brain metastases at presentation. The most common extracranial metastatic sites of the disease were lung (72.5%), bone (47.5%), lymph node (27.5%), and liver (12.5%). Twenty-four (60%) patients previously had received various therapies (tyrosine kinase inhibitor, checkpoint inhibitors, or palliative radiotherapy). After brain metastases developed, 92% of the patients received brain radiotherapy (whole-brain radiotherapy or stereotactic radiosurgery), and twenty-five (62.5%) patients received different therapies. Nine patient received sunitinib, nine patient pazopanib, five patient nivolumab, and two patient axitinib. A total of 32 (80%) patients died during the study period. The median OS was 8.8 months (range, 2.9-14.6) for all patients with bmRCC. Six months- and one-years overall survival ratios were 60% and 40%, respectively. In univariate analysis, the number of brain metastasis (p = 0.352), the localization of brain metastasis (p = 0.790), the longest size of brain metastasis (p = 0.454), the number of extracranial metastatic sites (p = 0.812), de-novo metastatic disease (p = 0.177), primary tumor localization (left or right) (p = 0.903), and tumor grade (p = 0.093) were not statistically significant factors on OS. However, age (p = 0.02), a history of nephrectomy (p &lt; 0.001), receiving brain radiotherapy (p = 0.005), and type of treatment (p = 0.044) was statistically significant. Only, the effect of brain radiotherapy on OS (p = 0.011) was confirmed in multivariate analysis. Conclusions: The prognostic data of patients with bmRCC is limited. In this study, we observed that the prognosis of patients with bmRCC was poor. Despite a small number of patients, we detected that the effect of tyrosine kinase inhibitors and nivolumab was comparable, and receiving brain radiotherapy was a prognostic factor for OS.