tbuckley/cabot-search huggingface dataset:
Managing the delivery of quality cancer care during the COVID-19 pandemic in a small community cancer clinic.
Authors: Kashyap B. Patel, Natasha Clinton
Journal: Journal of Clinical Oncology (2020)

45 Background: The global pandemic resulting from COVID-19 has resulted in over 400,000 deaths and nearly 7 million active cases at the time of writing this abstract (World Health Organization, 2020). This Public Health Emergency (PHE) represents an unprecedented challenge for oncologists and cancer patients alike. They are met with the challenge of providing uninterrupted care to cancer patients, a predicament that includes a balance between the use of immunosuppressive chemotherapy, it’s potential impact on contracting COVID-19 and the risk of cancer progression. Liang et al reported that cancer patients were not only at very high risk of contracting COVID -19, but also at a much higher risk of complications and death. Our medium sized oncology practice rapidly adapted to meet the challenge to continue to provide care. Methods: Employee and patient safety: Implement CDC recommendations in waiting room, infusion suites and supply of PPE. Categorize patients into priorities based on severity and need of treatment. Implement telehealth. Implement care in accordance to Cancer Patients Assessment and Treatment Priority Determination (top, intermediate and low priority)–Table. As a part of our initial strategy, we discussed the risk and balance of postponing chemotherapy or elective surgery for stable cancer patients during the first phase of closures. We also focused on more intensive surveillance in the older patient population or those with multiple high-risk comorbidities. For patients in complete remission on maintenance therapy, we balanced risk and benefit of stopping chemotherapy. In other patients, we considered the option of switching their chemotherapy regimen from IV to oral therapies, where clinically appropriate, to decrease the frequency of clinic visits and potential exposure. In cases where the option of non-immunosuppressive oral therapy is existed, we implemented the same. Results: Our clinic continues to provide uninterrupted care since the declaration of PHE. We saw a drop of 25% patient volume in March and 35% in April. However, with instant adaptation and implementation of CDC recommendations patient volume reached back to pre COVID 19 related emergency. None of our employees, their dependents nor any of our patients have contracted COVID-19 to date (according to DHEC feedback) at the time of writing. We had a total of 5082 patients visits (1261 chemo visits). Conclusions: By implementing the right steps and precautions, it is possible to provide continued care for and protect staff, physicians and patients. [Table: see text]
Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma
Authors: Jianjun Gao, Neema Navai, Omar Alhalabi, Arlene Siefker-Radtke, Matthew T. Campbell, Rebecca Slack Tidwell, Charles C. Guo, Ashish M. Kamat, Surena F. Matin, John C. Araujo, Amishi Y. Shah, Pavlos Msaouel, Paul Corn, Jianbo Wang, John N. Papadopoulos, Shalini S. Yadav, Jorge M. Blando, Fei Duan, Sreyashi Basu, Wenbin Liu, Yu Shen, Yuwei Zhang, Marc Daniel Macaluso, Ying Wang, Jianfeng Chen, Jianhua Zhang, Andrew Futreal, Colin Dinney, James P. Allison, Sangeeta Goswami, Padmanee Sharma
Journal: Nature Medicine (2020)
Use of patient-reported outcomes (PROs) to predict treatment outcomes in patients with advanced cancer.
Authors: Aparna Raj Parikh, Emily E. Van Seventer, Madeleine Fish, Kathryn Fosbenner, Katie Kanter, Amirkasra Mojtahed, Jill N. Allen, Lawrence Scott Blaszkowsky, Jeffrey William Clark, Jon S. Du Bois, Joseph Wang Franses, Bruce J. Giantonio, Lipika Goyal, Samuel J Klempner, Eric Roeland, David P. Ryan, Colin D. Weekes, Nora K. Horick, Ryan Bruce Corcoran, Ryan David Nipp
Journal: Journal of Clinical Oncology (2020)

186 Background: PROs assessing quality of life (QOL) and physical symptoms often correlate with clinical outcomes in patients (pts) with cancer. Yet, data are lacking about the use of PROs to predict treatment response. We evaluated associations of baseline PROs with treatment response, healthcare use, and survival among pts with advanced gastrointestinal cancer. Methods: We prospectively enrolled pts with metastatic gastrointestinal cancer prior to initiating chemotherapy at Massachusetts General Hospital. At baseline (start of treatment), pts reported their QOL (Functional Assessment of Cancer Therapy General [FACT-G], subscales assess QOL across 4 domains: functional, physical, emotional, social well-being) and symptom burden (Edmonton Symptom Assessment System [ESAS]). Higher scores on FACT-G indicate better QOL, while higher scores on ESAS represent a greater symptom burden. We used regression models to examine associations of baseline PRO scores with treatment response (clinical benefit [CB] or progressive disease [PD] at the time of first scan based on clinical documentation), healthcare use (unplanned hospital admissions), and survival. Results: From 5/2019-3/2020, we enrolled 112 of 131 (85.5% enrollment) consecutive pts (median age = 62.8, 61.6% male, 45.5% pancreatobiliary cancer). For treatment response, 64.3% had CB and 35.7% had PD. Higher ESAS-physical (B = 1.04, p = .027) and lower FACT-G functional (B = 0.92, p = .038) scores at baseline were significant predictors of PD. On the specific ESAS items, pts who experienced PD were more likely to report moderate/severe poor well-being (57.9% vs 29.7%; p = .001), pain (44.7% vs 25.0%; p &lt; .050), drowsiness (42.1% vs 20.3%; p = .024), and diarrhea (23.7% vs 4.7%; p = .008) at baseline. Lower FACT-G total (HR = 0.96, p = .003), FACT-G physical (HR = 0.89, p &lt; .001), FACT-G functional (HR = 0.87, p &lt; .001), and higher ESAS-physical (HR = 1.03, p = .028) scores at baseline were significantly associated with greater risk of hospital admission. Lower FACT-G total (HR = 0.96, p = .009), FACT-G emotional (HR = 0.87, p = .014), as well as higher ESAS-total (HR = 1.03, p = .018) and ESAS-physical (HR = 1.03, p = .040) scores at baseline were significantly associated with greater risk of death. Conclusions: We found that baseline PROs predict treatment response in pts with advanced cancer, namely physical symptoms and functional QOL, in addition to healthcare use and survival outcomes. These findings further support the use of PROs to predict important clinical outcomes, including the novel finding of treatment response.
Cholangioscopy findings in IgG4-related sclerosing cholangitis
Authors: Augusto Villaverde, Fernando Ignacio Giménez, Dante Manazzoni, Juan E. Pizzala, Victor H. Abecia, Manuel Alejandro Mahler, Mariano M. Marcolongo
Journal: Endoscopy (2020)

We present three cases of IgG4-related sclerosing cholangitis in association with autoimmune pancreatitis. The patients were all men and were aged 69, 71, and 75; their clinical presentations were with obstructive jaundice and considerable weight loss.
Hybrid gelatin/oxidized chondroitin sulfate hydrogels incorporating bioactive glass nanoparticles with enhanced mechanical properties, mineralization, and osteogenic differentiation
Authors: Lei Zhou, Lei Fan, Feng-Miao Zhang, Yuhe Jiang, Min Cai, Cong Dai, Yi-An Luo, Ling-Jie Tu, Zheng-Nan Zhou, Xiao-Jun Li, Cheng-Yun Ning, Kai Zheng, Aldo R. Boccaccini, Guo-Xin Tan
Journal: Bioactive Materials (2020)

Biopolymer based hydrogels are characteristic of their biocompatibility and capability of mimicking extracellular matrix structure to support cellular behavior. However, these hydrogels suffer from low mechanical properties, uncontrolled degradation, and insufficient osteogenic activity, which limits their applications in bone regeneration. In this study, we developed hybrid gelatin (Gel)/oxidized chondroitin sulfate (OCS) hydrogels that incorporated mesoporous bioactive glass nanoparticles (MBGNs) as bioactive fillers for bone regeneration. Gel-OCS hydrogels could be self-crosslinked in situ under physiological conditions in the presence of borax. The incorporation of MBGNs enhanced the crosslinking and accelerated the gelation. The gelation time decreased with increasing the concentration of MBGNs added. Incorporation of MBGNs in the hydrogels significantly improved the mechanical properties in terms of enhanced storage modulus and compressive strength. The injectability of the hydrogels was not significantly affected by the MBGN incorporation. Also, the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro and rat cranial defect restoration in vivo were significantly promoted by the hydrogels in the presence of MBGNs. The hybrid Gel-OCS/MBGN hydrogels show promising potential as injectable biomaterials or scaffolds for bone regeneration/repair applications given their tunable degradation and gelation behavior as well as favorable mechanical behavior and osteogenic activities.
IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8
Authors: Alba Sánchez-Fernández, Stephanie Zandee, Jesús Amo-Aparicio, Marc Charabati, Alexandre Prat, Cecilia Garlanda, Elan Z. Eisenmesser, Charles A. Dinarello, Rubèn López-Vales
Journal: Theranostics (2020)

Background: Interleukin 37 (IL-37), a member of IL-1 family, broadly suppresses inflammation in many pathological conditions by acting as a dual-function cytokine in that IL-37 signals via the extracellular receptor complex IL1-R5/IL-1R8, but it can also translocate to the nucleus. However, whether IL-37 exerts beneficial actions in neuroinflammatory diseases, such as multiple sclerosis, remains to be elucidated. Thus, the goals of the present study were to evaluate the therapeutic effects of IL-37 in a mouse model of multiple sclerosis, and if so, whether this is mediated via the extracellular receptor complex IL-1R5/IL-1R8. Methods: We used a murine model of MS, the experimental autoimmune encephalomyelitis (EAE). We induced EAE in three different single and double transgenic mice (hIL-37tg, IL-1R8 KO, hIL-37tg-IL-1R8 KO) and wild type littermates. We also induced EAE in C57Bl/6 mice and treated them with various forms of recombinant human IL-37 protein. Functional and histological techniques were used to assess locomotor deficits and demyelination. Luminex and flow cytometry analysis were done to assess the protein levels of pro-inflammatory cytokines and different immune cell populations, respectively. qPCRs were done to assess the expression of IL-37, IL-1R5 and IL-1R8 in the spinal cord of EAE, and in blood peripheral mononuclear cells and brain tissue samples of MS patients. Results: We demonstrate that IL-37 reduces inflammation and protects against neurological deficits and myelin loss in EAE mice by acting via IL1-R5/IL1-R8. We also reveal that administration of recombinant human IL-37 exerts therapeutic actions in EAE mice. We finally show that IL-37 transcripts are not up-regulated in peripheral blood mononuclear cells and in brain lesions of MS patients, despite the IL-1R5/IL-1R8 receptor complex is expressed. Conclusions: This study presents novel data indicating that IL-37 exerts therapeutic effects in EAE by acting through the extracellular receptor complex IL-1R5/IL-1R8, and that this protective physiological mechanism is defective in MS individuals. IL-37 may therefore represent a novel therapeutic avenue for the treatment of MS with great promising potential.
Clinical landscape of oncolytic virus research in 2020
Authors: Nicholas Macedo, David M Miller, Rizwan Haq, Howard L Kaufman
Journal: Journal for ImmunoTherapy of Cancer (2020)

Oncolytic viruses (OVs) are a new class of cancer therapeutics. This review was undertaken to provide insight into the current landscape of OV clinical trials. A PubMed search identified 119 papers from 2000 to 2020 with 97 studies reporting data on 3233 patients. The viruses used, presence of genetic modifications and/or transgene expression, cancer types targeted, inclusion of combination strategies and safety profile were reported. In addition, information on viral bioshedding across the studies, including which tissues or body fluids were evaluated and how virus was detected (eg, PCR, plaque assay or both), is also reported. Finally, the number of studies evaluating antiviral and antitumor humoral and cellular immune responses were noted. We found that adenovirus (n=30) is the most common OV in clinical trials with approximately two-thirds (n=63) using modified or recombinant viral backbones and granulocyte-macrophage colony-stimulating factor (n=24) was the most common transgene. The most common tumors targeted were melanoma (n=1000) and gastrointestinal (GI; n=577) cancers with most using monotherapy OVs given by intratumoral (n=1482) or intravenous (n=1347) delivery. The most common combination included chemotherapy (n=36). Overall, OV treatment-related adverse events were low-grade constitutional and local injection site reactions. Viral shedding was frequently measured although many studies restricted this to blood and tumor tissue and used PCR only. While most studies did report antiviral antibody titers (n=63), only a minority of studies reported viral-specific T cell responses (n=10). Tumor immunity was reported in 48 studies and largely relied on general measures of immune activation (eg, tumor biopsy immunohistochemistry (n=25) and serum cytokine measurement (n=19)) with few evaluating tumor-specific immune responses (n=7). Objective responses were reported in 292 (9%) patients and disease control was achieved in 681 (21.1%) patients, although standard reporting criteria were only used in 53% of the trials. Completed clinical trials not reported in the peer-reviewed literature were not included in this review potentially underestimating the impact of OV treatment. These data provide insight into the current profile of OV clinical trials reporting and identifies potential gaps where further studies are needed to better define the role of OVs, alone and in combination, for patients with cancer.
Covid-19: Experts advise cautious optimism for neutralising antibodies after early results
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Macrocycles are important drug leads with many advantages including the ability to target flat and featureless binding sites as well as act as molecular chameleons and thereby reach intracellular targets.However, due to their complex structures and inherent flexibility, macrocycles are difficult to study structurally and there are limited structural data available.Herein, we use the cryo-EM method MicroED to determine the novel atomic structures of several macrocycles which have previously resisted structural determination.We show that structures of similar complexity can now be obtained rapidly from nanograms of material, and that different conformations of flexible compounds can be derived from the same experiment.These results will have impact on contemporary drug discovery as well as natural product exploration.
A rare case of a biloma mimicking a submucosal tumor arising from the lower esophagus
Authors: Wen Liu, Sheng Wang, Jintao Guo, Xiang Liu, Nan Ge, Guoxin Wang, Siyu Sun
Journal: Endoscopy (2020)

A 57-year-old woman presented with intermittent abdominal pain of 5 months’ duration. Physical examination and laboratory tests were normal. Esophagogastroduodenoscopy showed a submucosal tumor (SMT) originating from the lower esophagus ([Fig. 1]). Endoscopic ultrasound (EUS) demonstrated a hypoechoic, homogeneous tumor (27 mm × 21 mm) with a regular margin arising from the muscularis propria ([Fig. 2]). Submucosal tunneling endoscopic resection (STER) was performed. After the tumor was revealed, an injection needle was used to pierce the tumor to prevent additional injury to the aorta: a golden-yellow liquid flowed out. A 10-mL sample of this liquid was taken for testing, and total bilirubin was found to be 146.3 µmol/L. An esophageal biloma was suspected. To avoid infection due to rupture of the biloma, we stopped the procedure. After hemostasis with hot biopsy forceps in the tunnel, several clips were used to close the mucosal defect ([Video 1]).
Antibiotic susceptibility reporting and association with antibiotic prescribing: a cohort study
Authors: Bradley J. Langford, Nick Daneman, Christina Diong, Alex Marchand-Austin, Kwaku Adomako, Arezou Saedi, Kevin L. Schwartz, Jennie Johnstone, Derek R. MacFadden, Larissa M. Matukas, Samir N. Patel, Gary Garber, Kevin A. Brown
Journal: Clinical Microbiology and Infection (2020)
Managing liver cirrhotic complications: Overview of esophageal and gastric varices
Authors: Cosmas Rinaldi Adithya Lesmana, Monica Raharjo, Rino A. Gani
Journal: Clinical and Molecular Hepatology (2020)

Managing liver cirrhosis in clinical practice is still a challenging problem as its progression is associated with serious complications, such as variceal bleeding that may increase mortality. Portal hypertension (PH) is the main key for the development of liver cirrhosis complications. Portal pressure above 10 mmHg, termed as clinically significant portal hypertension, is associated with formation of varices; meanwhile, portal pressure above 12 mmHg is associated with variceal bleeding. Hepatic vein pressure gradient measurement and esophagogastroduodenoscopy remain the gold standard for assessing portal pressure and detecting varices. Recently, non-invasive methods have been studied for evaluation of portal pressure and varices detection in liver cirrhotic patients. Various guidelines have been published for clinicians’ guidance in the management of esophagogastric varices which aims to prevent development of varices, acute variceal bleeding, and variceal rebleeding. This writing provides a comprehensive review on development of PH and varices in liver cirrhosis patients and its management based on current international guidelines and real experience in Indonesia.
Barriers to telehealth: The patient perspective.
Authors: Charles Douglas Bodine, Devika Govind Das, Karice Haywood, Morgan Khan
Journal: Journal of Clinical Oncology (2020)

266 Background: During the COVID-19 pandemic, the need for telehealth has come to the forefront of healthcare. In the right clinical context, telehealth is an easy and effective way for providers to deliver high quality care, while also taking away barriers to care access such as clinic inconvenience, distance traveled, financial toxicity, etc. An abundance of data exists regarding the benefits and potential of telehealth, but most data is from the perspective of the provider. Unfortunately, there is little information regarding the patient’s perspective and satisfaction; and even less regarding accessibility issues in terms of technology and cultural perception of telehealth. We postulate that there is a need for individualized grass root level understanding of the population being served to make sure telehealth adoption is sustained and equitable. We are studying this using a rapid cycle improvement project using a Plan Do Study Act format (PDSA), with a cohort of veterans in a medical oncology clinic in Birmingham, AL. Methods: We spoke with a pilot cohort of 67 patients in the medical oncology clinic at the VA Medical Center in Birmingham, AL. Surveys were done on all patients prior to their initial telehealth visit. Patients first agreed to participate, and then answered a 6-question survey regarding their perception of telehealth, their willingness to participate, and their perceived barriers to participation. We then identified barriers to intervene upon, with the plan to engage senior VA Leadership for the same. Results: 67 medical oncology patients in the Birmingham VA between May 1 and May 31, 2020, agreed to participate in a survey prior to their first telehealth appointment. We found that of the 67 patients surveyed, only 48 (71.6%) had a video capable phone and only 41 (61.2%) had high-speed internet or data to support that call. Interestingly 25 patients (37%) did not feel they could access the video on their own phone. While this presented one barrier to telehealth, we also found that 11 patients (16.4%) would not want to participate in telehealth even if they had a video capable device. Conclusions: This data, while not exhaustive, clearly captures some unique barriers to telehealth that may not have been previously studied or understood. Hearing the voice of the patient is critical in developing culturally competent forms of telehealth delivery. We will use this data to implement interventions that not only provide access of technology for our patients but will also make sure to specifically address the cultural/socioeconomic barriers to this form of healthcare distribution and how to overcome those barriers.
Abstract PO-033: Professional and psychological impact of COVID-19 pandemic on medical and radiation oncology residents: Results of a national survey
Authors: Marc Hilmi, Alice Boilève, Anabelle Ducousso, Morgan Michalet, Anthony Turpin, Cindy Neuzillet, Natacha Naoun
Journal: Clinical Cancer Research (2020)

Abstract Background: The COVID-19 pandemic deeply impacted clinical practices in oncology leading to organizational, ethical, and medical issues. It has raised challenges in a context of competing care priorities between COVID-19 and cancer treatment. Residents and fellows were in the front line and had to face difficulties related to increasing care needs and urgent reorganization of the health care system while managing stress and uncertainty. Methods: We conducted a national survey (39 questions) in France among all oncology and radiation therapy residents to describe psychological impact and difficulties encountered by residents (i.e., reassignment, training/research time, supervision, teleworking, management of patients) during the COVID-19 pandemic. Results: Overall, 222 residents (oncologists: 61% and radiation therapists: 39%) participated in our survey (representing around one third of all residents and fellows in France). Reassignment in COVID-19 wards involved 32% of respondents. Training and research activity were decreased for 89% and 41% of respondents, respectively. 70% have been confronted with ethical issues, 35% felt worried about their health, and 23% experienced psychological distress. According to the Hospital Anxiety and Depression Scale, 32% were anxious and 17% depressive. Consumption of tobacco, psychostimulants, and alcohol was increased in 45%, 40%, and 24%, respectively. Conclusion: French oncology residents were highly impacted by the COVID-19 pandemic in terms of training and emotions. This national survey can be used as a basis for improved management, medical reorganization, and training of residents during the COVID-19 pandemic, especially when further waves are not excluded. Citation Format: Marc Hilmi, Alice Boilève, Anabelle Ducousso, Morgan Michalet, Anthony Turpin, Cindy Neuzillet, Natacha Naoun. Professional and psychological impact of COVID-19 pandemic on medical and radiation oncology residents: Results of a national survey [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-033.