tbuckley/cabot-search huggingface dataset:
The efficacy and safety of targeting GM-CSF in arthritis
Authors: Vivian P Bykerk
Journal: The Lancet Rheumatology (2020)

The efficacy and safety of targeting GM-CSF in arthritisThree randomised controlled trials published in The Lancet Rheumatology evaluate the biology, clinical efficacy, and safety of otilimab, in patients with rheumatoid arthritis 1,2 and hand osteoarthritis. 3 Otilimab is a monoclonal anti body that binds to and blocks granulocytemacrophage colonystimulating factor (GMCSF) from connecting with its receptors that is being developed for treatment of rheumatoid arthritis.It is one of four GMCSF inhibitors undergoing clinical trials in humans; all are human ised monoclonal antibodies.Mavrilimumab targets the GMCSF α receptor; whereas otilimab, namilumab, and lenzilumab bind directly to GMCSF.Lenzilumab is being studied in asthma; whereas, the other three GMCSF inhibitors have shown efficacy in reducing disease activity and improving pain in patients with rheumatoid arthritis. 4 Targeting GMCSF is a novel therapeutic approach in rheu matoid arthritis, with all available therapies acting to reduce activity of haematopoietic cells. 5,6 By contrast, GMCSF mediates the differentiation of macrophages and granulocytes from myeloid cells and, in turn, dendritic cells.Myeloid cells promote cytokine produc tion, tissue damage, and upregulate chemokine (CC motif) ligand 17 (CCL17)-a mediator of peripheral nerve sensitisation thus far only seen in animal models. 4 These three proof ofconcept trials 1-3 are an exciting advance in the field.Christopher Buckley and colleagues 1 did a phase 2b dose finding study evaluating the clinical effects of five doses of otilimab (22•5 mg, 45 mg, 90 mg, 135 mg, or 180 mg) versus placebo.Patients with active rheumatoid arthritis and an inadequate response to at least 12 weeks of methotrexate (222 patients, 37 per group) received weekly subcutaneous injections for 5 weeks, which was reduced to every other week until week 50.Standardised otilimab dosing frequencies were used in all three trials.Patients who did not have the prespecified improve ments in disease activity at week 12 or 24 were transferred to otilimab 180 mg.The primary endpoint of Disease Activity Score28 for Rheumatoid Arthritis with Creactive protein (DAS28CRP) remission at week 24 was not achieved.However, this goal was unrealistic in the patient population assessed, given that the study was powered to detect a large 30% difference between otilimab and placebo.Patients were also assessed for a range of other clinical outcomes, including 20%, 50%, or 70% improvement in American College of Rheumatology
Author Correction: An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer’s disease
Authors: Raffaella Nativio, Yemin Lan, Greg Donahue, Simone Sidoli, Amit Berson, Ananth R. Srinivasan, Oksana Shcherbakova, Alexandre Amlie-Wolf, Ji Nie, Xiaolong Cui, Chuan He, Li-San Wang, Benjamin A. Garcia, John Q. Trojanowski, Nancy M. Bonini, Shelley L. Berger
Journal: Nature Genetics (2020)
Metastases from tracheal adenoid cystic carcinoma
Authors: Voon Shiong Ronnie Tan, Andrew Li, Ju Ee Seet, Pyng Lee
Journal: Thorax (2020)

<h3>Background</h3> Tumorous heterogeneity is a hallmark of tumor evolution and cancer progression, being a longstanding challenge to targeted immunotherapy. Ex vivo armed T cells (EATs) using IgG-(L)-scFv bispecific antibodies (BsAbs) are potent tumor-specific cytotoxic effectors. To improve the anti-tumor efficacy of EATs against heterogeneous solid tumors, we explored multi-antigen targeting approaches. <h3>Methods</h3> Ex vivo expanded T cells were armed with BsAbs built on the IgG-(L)-scFv platform, where an anti-CD3 (huOKT3) scFv was attached to the carboxyl end of both light chains of a tumor specific IgG. Multispecificity was created by combining monospecific EATs, combining BsAbs on the same T cell, or combining specificities on the same antibody. Three multi-antigens targeting EAT strategies were tested: (1) pooled-EATs (EATs each with unique specificity administered simultaneously) or alternate-EATs (EATs each with unique specificity administered in an alternating schedule), (2) dual-EATs or multi-EATs (T cells simultaneously armed with ≥2 BsAbs), and (3) TriAb-EATs (T cells armed with BsAb specific for two targets besides CD3 (TriAb)). The properties and efficiencies of these three strategies were evaluated by flow cytometry, in vitro cytotoxicity, cytokine release assays, and in vivo studies performed in BALB-<i>Rag2</i><sup>-/-</sup>IL-2R-<i>γc</i>-KO (BRG) mice xenografted with cancer cell line (CDX) or patient-derived tumor (PDX). <h3>Results</h3> Multi-EATs retained target antigen specificity and anti-tumor potency. Cytokine release with multi-EATs in the presence of tumor cells was substantially less than when multiple BsAbs were mixed with unarmed T cells. When tested against CDXs or PDXs, dual-EATs or multi-EATs effectively suppressed tumor growth without clinical toxicities. Most importantly, dual-EATs or multi-EATs were highly efficient in preventing clonal escape while mono-EATs or TriAb- EATs were not as effective. <h3>Conclusions</h3> Multi-EATs have the potential to increase potency, reduce toxicity, and overcome tumor heterogeneity without excessive cytokine release. Arming T cells with multiple BsAbs deserves further exploration to prevent or to treat cancer resistance.
On-site Multiplex PCR for CSF diagnostics in an Acute Hospital versus Referral to Reference Laboratories: Assessing Economic Factors, Length of Stay and Antimicrobial Stewardship.
Authors: R Barry, C Dempsey, L Barry, C Hooton, A O’ Connor, C Reynolds, M Cremin, SF Felsenstein, R Cunney, J Dean, GD Corcoran
Journal: Journal of Infection (2020)
Epidemiology and risk factors for heat illness: 11 years of Heat Stress Monitoring Programme data from the FIVB Beach Volleyball World Tour
Authors: Sebastien Racinais, Marine Alhammoud, Nada Nasir, Roald Bahr
Journal: British Journal of Sports Medicine (2020)

Objectives To analyse 11 years of FIVB heat stress-monitoring data to determine the relative influence of the different environmental parameters in increasing the likelihood of a heat-related medical time-out (MTOheat). Methods A total of 8530 matches were recorded. The referee measured air temperature, black globe temperature, relative humidity and wet-bulb globe temperature (WBGT) before the matches, and registered the MTOheat. The absolute humidity was computed at posteriori. Results There were 20 MTOheat cases, but only 3 resulted in forfeiting the match. MTOheat incidence was not statistically impacted by sex (p=0.59). MTOheat cases were more prevalent during the games played in Asia during the 4th quarter of the year (p&lt;0.001). Two cases of MTOheat experienced diarrhoea or gastroenteritis during the 5 preceding days; both of them forfeited the match. A principal component analysis showed a specific environmental profile for the matches with MTOheat. They occurred at higher WBGT, temperatures and absolute humidity (p&lt;0.001), but with a lower relative humidity (p=0.027). Conclusions The current data showed that an increase in ambient or black globe temperature, but not relative humidity, increased the risk of a MTOheat; but that the absolute risk remained low in elite beach volleyball players. However, suffering or recovering from a recent illness may represent a risk factor for a MTOheat to lead to player forfeit.
Triggering interferon signaling in T cells with avadomide sensitizes CLL to anti-PD-L1/PD-1 immunotherapy
Authors: Nikolaos Ioannou, Patrick R. Hagner, Matt Stokes, Anita K. Gandhi, Benedetta Apollonio, Mariam Fanous, Despoina Papazoglou, Lesley-Ann Sutton, Richard Rosenquist, Rose-Marie Amini, Hsiling Chiu, Antonia Lopez-Girona, Preethi Janardhanan, Farrukh T. Awan, Jeffrey Jones, Neil E. Kay, Tait D. Shanafelt, Martin S. Tallman, Kostas Stamatopoulos, Piers E. M. Patten, Anna Vardi, Alan G. Ramsay
Journal: Blood (2020)
The Negative U Wave
Authors: James W. Salazar, Nora Goldschlager
Journal: JAMA Internal Medicine (2020)

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Sarcopenia and blood myokine levels as prognostic biomarkers in patients with liver cirrhosis or hepatocellular carcinoma
Authors: Sooyeon Oh, Jooho Lee
Journal: Clinical and Molecular Hepatology (2020)

See the Original "The association of the serum levels of myostatin, follistatin, and interleukin-6 with sarcopenia, and their impacts on survival in patients with hepatocellular carcinoma" on page 492.
Abstract PO-032: Patient-centered communication: Collaborative learning and communication strategies for patients and health care providers in the new normal of COVID-19
Authors: Martha Raymond, Margaret-Ann Simonetta
Journal: Clinical Cancer Research (2020)

Abstract Background: Data from the National Cancer Institute’s Surveillance, Epidemiology &amp; End Results (SEER) program estimate that in 2020 over 1.8 million new cancer diagnoses will occur. SEER data also indicate that over 15.5 million patients/survivors are currently living with a cancer diagnosis in the United States. Amid COVID-19, transitioning care beyond the clinic to minimize exposure for patients and health care providers is essential. Now more than ever, new and evolving ways to communicate openly and effectively are crucial for patients and their health care team. Methods: In March-May, 2020, the Raymond Foundation hosted nationwide virtual focus groups and town halls for cancer patients, survivors, and caregivers to gain a better understanding of how COVID-19 is affecting their cancer care, communication with their health care team, and shared decision-making. Primary goals included reaching patients in rural, urban, and community oncology settings to gain perspective from diverse populations. Results: 489 patients, survivors, and caregivers (54% female, 46% male) provided the following insights: 89% reported communication with their health care team had deteriorated since the pandemic; 94% indicated the need for increased communication with their health care team; 42% had a general knowledge of telehealth while 58% had little to no knowledge; 98% indicated they would like to learn more about telehealth options and would try this advanced class of service if offered by their health care team; 64% reported they were not able to accurately communicate treatment adverse effects leading to increased suffering; and 96% reported increased isolation and fear of the unknown care landscape. Conclusion: Cancer patients realize the importance of patient-centered communication to facilitate a personalized dialogue to actively participate in their care. Empowering patients with the skills they require to comprehensively perceive telemedicine, virtual care, and remote monitoring will help minimize patient risk and provide an opportunity for patients to engage with their health care team throughout the care continuum. Implementing strategies to skillfully serve patients via telemedicine and teleconferencing may be the new normal as we virtually revive the classic house call. Citation Format: Martha Raymond, Margaret-Ann Simonetta. Patient-centered communication: Collaborative learning and communication strategies for patients and health care providers in the new normal of COVID-19 [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-032.
Cross-Linking Assisted Infection Reduction: One-year Follow-up of a Randomized Clinical Trial Evaluating Cross-Linking for Fungal Keratitis
Authors: N. Venkatesh Prajna, Naveen Radhakrishnan, Prajna Lalitha, Ariana Austin, Zijun Liu, Jeremy D. Keenan, Travis C. Porco, Tom M. Lietman, Jennifer Rose-Nussbaumer
Journal: Ophthalmology (2020)
Patient-reported outcomes in routine oncology care: Perceptions, execution, and barriers.
Authors: Ajeet Gajra, Yolaine Jeune-Smith, Ting-Chun Yeh, Stephanie Fortier, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2020)

162 Background: There has been an increased emphasis on patient-reported outcomes (PROs) in recent oncology trials, and the benefits of incorporating PRO assessments during routine care have been established. The aim of the present study was to assess the perceptions, adoption and barriers to implementation of PROs in community practices during routine care. Methods: A live meeting in September 2019 surveyed US-based community oncology health care providers (HCPs), including medical oncologists/hematologists and advanced practice providers (APPs; defined as nurse practitioners and physician assistants) regarding their perceptions of PROs and their adoption of PROs during routine patient care. Participants completed both a web-based premeeting survey and live queries captured via audience response system. Data were summarized using descriptive statistics. Results: 71 HCPs (51 medical oncologists/hematologists and 20 APPs) participated. HCPs described their practices as: urban 50%, suburban 37%, and rural 13%. Over 80% reported having collected PRO data from their patients. Over 90% indicated that PROs are important to guide their treatment of patients, irrespective of the data sources (clinical studies or in real-world). Commonly collected PRO data included disease symptoms (66%), activities of daily living (62%), physical function (61%) and adverse events (59%). The NCCN Distress Thermometer (41%) was reported as the most common PRO instrument used during routine oncology care (Table). Despite understanding the importance of implementing PROs, 54% indicated that more resources (software and incentive systems) are needed, and 53% said that discussing PRO results with each patient is critical to facilitate the collection and utilization of PRO data. 84% were unaware of results of a seminal study which demonstrated that PROs improve quality of life and survival (Basch et al 2016, 2017). Conclusions: Most of the community oncology providers surveyed collected PRO data and acknowledged its value. However, more resources are needed to increase collection and use of PROs during routine care. Education directed towards community oncology providers is needed to highlight the value that PROs can add in cancer care. [Table: see text]
Reducing burdens of site feasibility assessments for conducting clinical trials.
Authors: Dax Kurbegov, Patricia A. Hurley, David Michael Waterhouse, Grzegorz S. Nowakowski, Edward S. Kim
Journal: Journal of Clinical Oncology (2020)

300 Background: Current methods to assess site feasibility for industry-funded clinical trials are onerous and delay patient access to novel treatment options and high-quality clinical trials. Industry sponsors and contract research organizations (CROs) often probe for unnecessary and/or duplicative information. These burdens prolong trial start-up times and are a barrier to site participation in oncology trials. The American Society of Clinical Oncology (ASCO) Research Community Forum convened a task force to identify ways to improve the site feasibility assessment process. Methods: Data were collected in 3 steps: 1) survey to assess site burdens, 2) collation of sample feasibility questionnaires (FQs), and 3) stakeholder meeting to discuss potential solutions. The task force then developed recommendations for process improvements and obtained stakeholder feedback through a survey. Results: 113 oncology practices (66 community, 47 academic) reported completing a median 5 FQs and 2 pre-study site visits (PSSVs) per month. FQs took a median 2 hours to complete whereas PSSVs took a median 4 hours to complete. Most considered FQ (81%) and PSSV (91%) content redundant to information previously provided, and FQs similar between different sponsors (86%). The median time from first contact to first patient enrolled was 6 months. The 40 respondents to the stakeholder survey represented 19 academic- and 9 community-based sites, 8 industry sponsors, and 4 CROs. Most preferred a model with a short FQ plus a PSSV when there was not a prior relationship. If there was a prior relationship, either a PSSV or teleconference was preferred. All stakeholders identified time savings, expedited start-up, fewer staff resources, and cost savings as the greatest benefits. The greatest barriers to adoption were buy-in from sponsors and CROs, and insufficient information about site capabilities. Conclusions: Site feasibility assessments for industry-sponsored trials are important to ensure patient safety and access to high quality clinical trials. However, current methods are inefficient and time and resource intensive. This initiative provided insights about challenges for sites and the viability of a fundamental change to site feasibility assessments. ASCO recommendations are forthcoming on improving processes, standardizing and minimizing questions, and using portals that are effective across all trials and clinical research scenarios.
Using MammaPrint to reduce the needfor chemotherapy in early breast cancer during theCOVID-19 pandemic
Authors: E. M. Murray, E. J. Myburgh, E. Lujinovic, L. Mittempergher, D. J. Robertson, J. J. De Jager, M. J. Kotze
Journal: Clinical Cancer Research (2020)

Introduction: With the recent worldwide outbreak of COVID-19, it became clear that certain comorbidities areassociated with an increased risk of complications and death  Several publications have reported an increased rateof ICU admission and mortality in cancer patients  This has led to guidelines advising more conservativeapproaches to cancer therapy, including chemotherapy  In the absence of prospective, disease-specific outcomedata, there is a risk of overestimating the risk of COVID-19 and thus increasing cancer-specific mortality or ofunderestimating  MammaPrint has been validated for selecting clinically high-risk breast cancer patients in whomchemotherapy can be avoided safely  Methods: We evaluated the current published literature related to the potential risk of breast cancer andchemotherapy in association with COVID-19  We estimated the potential risk of severe events in COVID-19 breastcancer patients receiving adjuvant chemotherapy to assess whether MammaPrint could help us further in makingchemotherapy decisions specific to an infectious epidemic risk  Results: The risk of COVID-19 morbidity and mortality in patients receiving chemotherapy could be greater than 1 5to 2 times higher than usual  However, other associated conditions frequently found in the breast cancer populationseem to still play a significant role in a worse outcome  We found no data to quantify the effect of chemotherapy ordata allowing us to adapt the MammaPrint Score to risk in an infectious epidemic  Conclusion: Adjuvant chemotherapy carries a potential risk for morbidity and mortality  Data from the currentliterature do not show the magnitude of the added risk for breast cancer patients on adjuvant chemotherapy inassociation with SARS Cov-2 infection  By using MammaPrint in hormone receptor-positive patients with up to threenodes in whom chemotherapy is considered, the treatment-related risk can be limited, allowing safe de-escalation oftherapy without increased cancer-specific mortality  We plan to pursue the statistical question of how the level of riskat any of the sites on the spectrum relates to distant metastasis-free survival so that mortality risks can be betterestimated during an infection
Real-world utilization of quality-of-life data: Perspectives from community oncology providers.
Authors: Bruce A. Feinberg, Jonathan Kish, Yolaine Jeune-Smith, Ting-Chun Yeh, Stephanie Fortier, Ajeet Gajra
Journal: Journal of Clinical Oncology (2020)

286 Background: Quality of life (QoL) is commonly assessed in oncology clinical trials. However, it is unclear if oncology healthcare providers (HCPs) perceive value in these metrics or if they impact clinical practice. We sought to assess the real-world utilization of QoL data and barriers to its adoption among US community oncology providers. Methods: Medical oncologists/hematologists, and advanced practice providers (APPs) participated in a survey to assess their perceptions and the utility of QoL data for routine practice during a live meeting in September 2019. Responses were captured via a web-based premeeting survey and an audience response system during the live meeting. Participant characteristics and responses were summarized using descriptive statistics. Results: A total of 71 HCPs (51 physicians and 20 APPs) participated. Regarding perceptions of QoL in oncology, 50% of physicians and 32% of APPs reported aligning with the sentence “It is important to have QoL, but efficacy is obviously the most critical endpoint.” HCPs reported that QoL may outweigh overall survival (OS) in certain clinical scenarios, such as in end-of-life (81%), frail patients (67%), or metastatic tumors (62%). When selecting between two agents with similar efficacy, safety was the most important factor (78%), followed by QoL (40%). 64% of physicians utilized aggregate QoL data from registrational trials or real-world studies to keep informed about QoL of different treatments, while 69% of APPs relied on their personal or practice experiences. 85% of physicians and 84% of APPs responded that it is important to perform formal QoL assessments during routine patient visits. 88% of HCPs expected that QoL/patient-reported outcomes (PRO) collection will increase their workload. Patient burden (58%) and provider resources (43%) were other barriers for QoL/PRO collection. HCPs were largely split regarding their understanding of QoL versus PRO, with 34% reporting that PRO was a subset of QoL and 28% reporting that QoL was a subset of PRO. Conclusions: Efficacy and safety are prioritized as clinical endpoints among oncology HCPs; however, there are certain clinical scenarios where QoL may provide more impactful data for HCPs in managing patients. Barriers remain to successful collection of QoL, and there is a need for further education among HCPs regarding PROs and QoL.