tbuckley/cabot-search huggingface dataset:
P13.16 Metastatic potential of systemic glioblastoma stem cell lines <i>in vivo</i>
Authors: S G Schwab, K Sarnow, F A Thorsen, J A Hossain, R Goldbrunner, H Miletic, R Bjerkvig
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Despite aggressive tumor behavior, extracranial metastases rarely develop in glioblastoma (GBM) patients. Two potential explanations have been suggested: 1) The blood-brain-barrier functions as a physical barrier that prevents the dissemination of GBM cells out of the central nervous system (CNS) or 2) that extracranial metastasis do occur, but the patients die before extracranial metastases manifest themselves. The first theory has been questioned based on the fact that circulating tumor cells (CTC) were found in blood samples of GBM patients without systemic metastases. To date it has not been proven if CTCs are able to reenter the brain and to what extent they are able to form systemic extracranial metastatic lesions. Therefore, the current study aimed at analyzing the dissemination patterns and the underlying mechanisms associated with the ability of GBM CTCs to form extracranial metastases. MATERIAL AND METHODS Five highly characterized human GBM stem cell (GSC) lines (P3, BG5, BG7, GG6, GG16), displaying GBM CNV patterns, were intracranially implanted in a first cohort, then transduced with a lentiviral Firefly Luciferase-eGFP vector and injected into the left cardiac ventricle of NOD/SCID mice in a second cohort. Mice were observed closely and tumor burden was assessed using in vivo as well as ex vivo bioluminescence imaging, MRI and PET. Mice were euthanized when the objective endpoint criteria (tumor burden) was met, then organs were harvested and fixed for further analysis. RESULTS First, a detailed characterization of the GSC line invasion patterns were assessed when grown as orthotopic xenografts in vivo dividing them into three categories: 1) Highly invasive without apparent angiogenesis (BG5) 2) Invasive with perivascular infiltration and angiogenesis (P3, BG7 and GG16) and 3) Angiogenic and highly circumscribed (GG6). Following intracardial injection, (7 out of 8) P3 animals developed extracranial and intracranial tumors with a distinctive pattern. Brain, adrenal gland, ovary and liver were amongst the organs most susceptible for tumor growth in the P3 group. For the BG5 and BG7 cell lines, no metastases were observed whereas only 1 animal out of 10 developed metastases in both groups GG16 and GG6. CONCLUSION Only one out of 5 GSC lines exhibited a strong metastatic potential when injected into the left cardiac ventricle. Compared to other tumors which exhibit a strong metastatic potential from the circulation, GSC lines do only to a very limited extent show this potential reflecting observations made in the clinic.
Assessing oncology patient and provider telehealth experience.
Authors: Kelly Eng, Caitlin C. Donohue, Andrew J. Wagner, David W. Dougherty, Elahi Salehi, Carol Lowenstein, Daniel A. Gundersen, Ruth Lederman, Sarah Kadish
Journal: Journal of Clinical Oncology (2021)

284 Background: Due to COVID-19, telehealth volume at our comprehensive cancer center rose from less than 5% of exam visits to over 25% in April 2020. We sought to understand the experience of telehealth and compare it to in-person experiences for patients and providers (physicians, nurse practitioners, and physician assistants) to identify areas for improvement. Methods: A multidisciplinary team adapted our existing patient satisfaction survey to incorporate telehealth, defined as phone and video exam visits. A technology section was created to assess aspects unique to telehealth. Questions about the patient-provider experience were the same for telehealth and in-person visits. A provider experience survey was conducted during a two-week period in May and June 2020. The provider survey aligned questions with the patient survey to compare the perceptions of the provider-patient interaction. Results: Patient experience scores for in-person and telehealth visits were comparable, with a slightly higher mean score for in-person visits. The mean scores for patient perception of care given at our cancer center was 97.5 (n=11,969) and 96.9 (n=4670) and the likelihood to recommend was 97.8 (n=12,072) and 97.4 (n=4,398) for in-person and telehealth, respectively, between June and December 2020. Patient feedback prioritized addressing technical barriers. We implemented several interventions and increased the telehealth technology section mean scores from 93.2 (n=1,095) to 95.2 (n=700) between June and December 2020. When comparing the percent of respondents scoring good or very good, provider scores showed sizable gaps between in-person and telehealth experiences on all questions (see table). The question “degree to which the care team was well coordinated” had the largest difference between in-person and telehealth scores for both patients and providers. Several interventions to adapt staffing and workflows have been implemented to improve care telehealth coordination. Conclusions: While patients reported similar satisfaction between in-person and telehealth visits, increasing coordination remains vital to improving the experience for both patients and providers. Furthermore, understanding the gap in the provider experience between in-person and telehealth is critical for successful adoption of telehealth as a long-term strategy for healthcare delivery.[Table: see text]
OS14.6.A GlioCova: Defining patient safety events for brain tumour patients undergoing neurosurgery
Authors: R Mauricaite, K Le Calvez, A Brodbelt, A Bottle, M Williams
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Surgery is associated with a risk of adverse events (e.g. venous thrombosis). These have been used to define the OECD Patient Safety Event (PSE) indicators (41 diagnostic codes), but not in the brain tumour population. The GlioCova project uses English linked national cancer data on all 51,775 adult primary brain tumour patients (2013–2018). MATERIAL AND METHODS We identified all glioblastoma patients having surgery for their tumour and noted the 100 most common ICD-10 diagnostic codes within 30 days of surgery, excluding previous medical conditions, brain tumour diagnosis codes and OECD-defined codes. Potential post-surgical complications were reviewed by a group of experienced clinicians. We reviewed these “novel PSE codes” in all brain tumour patients re-admitted after surgery. We looked at the co-occurrence between our novel and OECD codes and combined them to form the final PSE list.Patients readmitted within 30 days were divided into those without codes (“PSE-free”), and those with at least one PSE code during admission or readmission. We examined age, length of stay, in-hospital and 30-day mortality and assessed statistical significance using Welch’s t-test and a two sample Z-test for proportions. RESULTS 29,135 patients underwent neurosurgery, of whom 8,361 (28.7%) were readmitted within 30 days. We identified 32 novel PSE codes. 1,319 (16%) patients had an OECD code, 5,524 (66%) had a novel code, and 2,098 (25%) patients were PSE-free. 83% of patients who had an OECD PSE code also had a novel code. Patients in the PSE group were older (median age = 60 years) than the PSE-free group (57 years). Length of stay was longer in patients who had a PSE after surgery (median = 7 days) and after readmission (5 days) compared with PSE-free after surgery (4 days), at readmission (0 days). More patients died in hospital after readmission in the PSE group (4.7%) compared with no-PSE (2.7%). 30-day mortality after surgery was similar in both groups (2.5% PSE-free, 3.1% PSE group). All differences were highly statistically significant (p&amp;lt;0.0001). CONCLUSION We identified 32 novel patient safety event codes following surgery in the brain tumour population. Patients with these diagnostic codes had an elevated LOS and in-hospital death rate. Using brain tumour specific PSE codes captures many more events than the existing list of OECD codes.
Biomarker testing patterns in patients with stage IV non-small cell lung cancer (NSCLC) in U.S. community-based oncology practice setting.
Authors: Anthony Sireci, Peter M Krein, Lisa M. Hess, Taha Khan, Joanne P. Willey, Michael Ayars, Kathryn Deyoung, Sandya Bhaskhar, Ganiat Mumuney, Anna D. Coutinho
Journal: Journal of Clinical Oncology (2021)

300 Background: This study evaluated rates of biomarker testing for patients with stage IV non-squamous NSCLC, which is known to have a ̃40% biomarker-positive rate (AMP, 2020), in a community-based oncology practice setting in the United States (US). Methods: A retrospective study was performed using data from a US electronic medical record database of patients aged ≥18 years with an initial diagnosis (index dx) of stage IV non-squamous NSCLC between Jan 1, 2015 and Dec 31, 2019. Unstructured data on molecular biomarker testing (single-gene and next-generation sequencing [NGS]-based) were abstracted from patient charts utilizing Natural Language Processing for EGFR mutation, ALK rearrangement, BRAF mutation, ROS1 rearrangement, MET exon14 mutation, RET fusion, NTRK fusion, and PD-L1 expression. Systemic therapy was obtained from structured data. Data were summarized using descriptive statistics. This study received a waiver of consent from Advarra IRB. Results: Of 646 patients identified in the database, 500 met all inclusion criteria and are included in this analysis. The majority (73.8%) were diagnosed in 2018 (n = 162; 32.4%) and 2019 (n = 207; 41.4%). Mean age (SD) was 70.0 (10.1) years, with 53.2% female. A total of 447 (89.4%) were tested for at least one biomarker after index diagnosis of which 81.2% (n = 406) had at least one single-gene test; 54.8% (n = 274) had an NGS test and 66.8% were tested for PD-L1. Single-gene or NGS-based testing was &gt; 85% of patients across all index years. The use of NGS-based tests ranged from 35.0% among patients whose first diagnosis was in 2015 to 59.4% in 2019. Overall, 85.4% (n = 427) of the cohort received first-line treatment with chemotherapy (53.6%), immunotherapy (48.2%), or targeted therapy (14.2%). Among patients who received biomarker tests, 15.4% received targeted treatment and 49.7% received immunotherapy treatment, including checkpoint inhibitors, during first-line treatment. Conclusions: NGS testing utilization increased during the study period and by 2019, 59% of patients received NGS-based testing. Opportunities persist for practices to improve testing and achieve guideline recommendations. PD-L1 biomarker testing was performed amongst the highest proportion of patients in this study and nearly 50% of all patients received immunotherapy, including checkpoint inhibitors. Targeted therapy was used in 14.2% of this population, suggesting that patients with actionable biomarkers may not be receiving targeted treatment for their disease, potentially due to gaps in testing among patients in this dataset.
P-129 Concomitant RAS and BRAF mutations: Impact on overall survival and progression free survival in metastatic colorectal cancer patients
Authors: A. Pretta, M. Persano, G. Pinna, C. Donisi, E. Cimbro, A. Parrino, M. Migliari, M. Dubois, S. Mariani, N. Liscia, E. Lai, V. Pusceddu, M. Puzzoni, P. Ziranu, M. Scartozzi
Journal: Annals of Oncology (2021)
Evaluation of Epidural Analgesia Use During Labor and Infection in Full-term Neonates Delivered Vaginally
Authors: Lijie Jia, Huimin Cao, Yuna Guo, Ying Shen, Xiaoyu Zhang, Zhou Feng, Jiangruixuan Liu, Zhongcong Xie, Zifeng Xu
Journal: JAMA Network Open (2021)

Quantification of potential consequences associated with the use of epidural analgesia during labor could help to improve the safety and quality of labor and delivery care for parturient women.To evaluate the association between epidural analgesia use during labor and neonatal infection in a large cohort of parturient women.This propensity score-matched cohort study was conducted at a university-affiliated hospital in Shanghai, China. Women at full-term pregnancy undergoing vaginal delivery between January 2013 and October 2018 were included in the study. Parturient women who were parous, experiencing premature delivery (gestational age <37 weeks), were pregnant with more than 1 fetus, or had experienced a stillbirth were excluded. Data were analyzed from October 2019 to June 2020.The use of epidural analgesia during labor.The primary outcome was the incidence of neonatal infection, including neonatal sepsis, neonatal uncharacterized infection, neonatal pneumonia, and neonatal necrotizing enterocolitis reported in the medical record. Secondary outcomes included the incidence of maternal intrapartum fever and histologic chorioamnionitis.Among 37 786 parturient women included (mean [SD] age, 29.5 [3.0] years), 19 968 (52.8%) received epidural analgesia during labor. In the propensity score-matched cohort (including 15 401 parturient women in each group), use of epidural analgesia was associated with a higher incidence of neonatal infection (absolute risk difference, 2.6%, 95% CI, 2.2%-3.0%; relative risk [RR], 2.43; 95% CI, 2.11-2.78), including higher incidence of sepsis (absolute risk difference, 0.1%, 95% CI, 0.1%-0.2%; RR, 3.50; 95% CI, 1.73-7.07) and uncharacterized infection (absolute risk difference, 2.2%, 95% CI, 1.9% to 2.6%; RR, 2.69; 95% CI, 2.30-3.15), compared with no epidural analgesia use. Use of epidural analgesia was also associated with greater incidence of maternal intrapartum fever (RR, 4.12; 95% CI, 3.78-4.50) and histologic chorioamnionitis (RR, 4.08; 95% CI, 3.59-4.64) compared with no epidural analgesia use.This cohort study found that use of epidural analgesia in full-term nulliparous women undergoing vaginal delivery was associated with an increased risk of neonatal infection, pending further investigation. These findings support efforts to further improve safety and quality of labor and delivery care for parturient women.
Author Correction: Dynamic regulation of hypoxia-inducible factor-1α activity is essential for normal B cell development
Authors: Natalie Burrows, Rachael J. M. Bashford-Rogers, Vijesh J. Bhute, Ana Peñalver, John R. Ferdinand, Benjamin J. Stewart, Joscelin E. G. Smith, Mukta Deobagkar-Lele, Girolamo Giudice, Thomas M. Connor, Akimichi Inaba, Laura Bergamaschi, Sam Smith, Maxine G. B. Tran, Evangelia Petsalaki, Paul A. Lyons, Marion Espeli, Brian J. P. Huntly, Kenneth G. C. Smith, Richard J. Cornall, Menna R. Clatworthy, Patrick H. Maxwell
Journal: Nature Immunology (2021)
Experienced barriers of care within European treatment seeking transgender individuals: A multicenter ENIGI follow-up study
Authors: Maeghan B. Ross, Tim C. van de Grift, Els Elaut, Timo O. Nieder, Inga Becker-Hebly, Gunter Heylens, Baudewijntje P. C. Kreukels
Journal: International Journal of Transgender Health (2021)

To evaluate the experienced barriers of care for treatment-seeking trans individuals (TSTG) in three large European clinics.
Incidental Detection of Sacral Insufficiency Fracture on 68Ga-FAPI PET/MR
Authors: Yuhu Lv, Xiaoli Lan, Chunxia Qin
Journal: Clinical Nuclear Medicine (2021)

A 61-year-old woman with low-set rectal adenocarcinoma (cT4bN1Mx) received radiotherapy and chemotherapy for 4 months, and then she underwent 18F-FDG PET/CT and 68Ga-FAPI PET/MR. Obviously increased 68Ga-FAPI uptake was unexpectedly revealed on both sides of the sacrum with low 18F-FDG uptake, which was diagnosed as insufficiency fracture based on the imaging features, advanced patient age, and radiotherapy history. The possibility of insufficiency fracture should be considered when accidental, symmetrically increased sacral 68Ga-FAPI uptake appears in cancer patients, and differential diagnosis should be carefully made.
French to take legal action against drug regulator over levothyroxine
Authors: Barbara Casassus
Journal: BMJ (2021)

Hundreds of patients in France are expected to join a legal challenge against the country’s medicines agency in the latest attempt to obtain redress for the adverse side effects they experienced from Merck’s reformulated levothyroxine drug more than four years ago.

On 14 September lawyer Christophe Leguevaques of MySMARTcab will launch the French equivalent of a class action suit against the National Agency for the Safety of Medicines and Health Products (ANSM) for failing to protect French patients from health risks because of the change. Most of the patients are women.

“We hope at least 1000 people will join the suit,” Leguevaques told The BMJ . The investigating magistrate has received more than 10 000 …
Iron deficiency in JAK2 exon12 and JAK2-V617F mutated polycythemia vera
Authors: Dan Liu, Zefeng Xu, Peihong Zhang, Tiejun Qin, Bing Li, Shiqiang Qu, Lijuan Pan, Wenyu Cai, Jinqin Liu, Huijun Wang, Qi Sun, Xiujuan Sun, Meng Jiao, Qingyan Gao, Zhongxun Shi, Huijun Huang, Gang Huang, Robert Peter Gale, Zhijian Xiao
Journal: Blood Cancer Journal (2021)
P14.54 Primary central nervous system lymphoma of the spinal cord: a LOC network cohort study
Authors: N Valyraki, G Ahle, E Tabouret, R Houot, F Jardin, H Ghesquieres, S Choquet, M Moles, K Hoang-Xuan, C Houillier
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) mainly affects the brain (&amp;gt;90% of the cases), Very little data can be found in the literature on PCNSL with spinal cord localization. MATERIAL AND METHODS We present a retrospective study based on the French LOC network database. We selected adult immunocompetentpatients, with a histological or cytological diagnosis of PCNSL, and a spinal cord localization at initial diagnosis. RESULTS Of the 2043 PCNSLof the LOC database newly diagnosed since 2011, 14 patients (9 men, median age 68, median Karnofsky performance status 50%)met the selection criteria. The median diagnostic delay was 82 days (min 15-max 1080) compared to 35 days in primary cerebral lymphomas. At diagnosis, walking was impossible in 7/14 patients and 5/14 had indwelling urinary catheter. On MRI, 100% had enlargement of the spinal cord with homogeneous contrast enhancement in 13/14 cases. Spinal cord lesions were unique in 9/14 patients and multiples in 5/14 patients. CSF IL10 level was increased in 6/7 patients. Brain lesions were found in 9/14 patients, located in the posterior fossa in 5/9 cases. The diagnosis was made either on a brain biopsy (N=6), a spinal cord biopsy or surgery (N=5) or the cytologic analysis of the CSF (N=3).4/5 patients had neurological sequel after spinal cord biopsy or surgery. All the patients were treated by high-dose methotrexate-based chemotherapy, followed by spinal cord irradiation (N=1) or autograft (N=2). There was an overall response rate of 71% (complete response in 8/14). 8/14 patients relapsed, 5 in the brain, 2 in the spinal cord, and 1 both in the spinal cord and in the brain. 2-year PFS and OS were 45% and 64%, respectively. Among the long-term responders, 50% remained in wheel chair, while only 10% could walk normally. CONCLUSION Considering the high risk of a spinal cord biopsy,the rarity of the disease, as well as the numerous differential diagnoses, the diagnosis of spinal cord lymphoma is difficult. Searching for other lymphomatous locations or assaying CSF IL10 may be helpful in this disease where delay in diagnosis is often prolonged et can cause irreversible handicap.
Bispecific binder redirected lentiviral vector enables in vivo engineering of CAR-T cells
Authors: Justin T Huckaby, Elisa Landoni, Timothy M Jacobs, Barbara Savoldo, Gianpietro Dotti, Samuel K Lai
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Chimeric antigen receptor (CAR) T cells have shown considerable promise as a personalized cellular immunotherapy against B cell malignancies. However, the complex and lengthy manufacturing processes involved in generating CAR T cell products ex vivo result in substantial production time delays and high costs. Furthermore, ex vivo expansion of T cells promotes cell differentiation that reduces their in vivo replicative capacity and longevity. Methods Here, to overcome these limitations, CAR-T cells are engineered directly in vivo by administering a lentivirus expressing a mutant Sindbis envelope, coupled with a bispecific antibody binder that redirects the virus to CD3 + human T cells. Results This redirected lentiviral system offers exceptional specificity and efficiency; a single dose of the virus delivered to immunodeficient mice engrafted with human peripheral blood mononuclear cells generates CD19-specific CAR-T cells that markedly control the growth of an aggressive pre-established xenograft B cell tumor. Conclusions These findings underscore in vivo engineering of CAR-T cells as a promising approach for personalized cancer immunotherapy.
Management and Outcomes of Cardiogenic Shock in Cardiac ICUs With Versus Without Shock Teams
Authors: Alexander I. Papolos, Benjamin B. Kenigsberg, David D. Berg, Carlos L. Alviar, Erin Bohula, James A. Burke, Anthony P. Carnicelli, Sunit-Preet Chaudhry, Stavros Drakos, Daniel A. Gerber, Jianping Guo, James M. Horowitz, Jason N. Katz, Ellen C. Keeley, Thomas S. Metkus, Jose Nativi-Nicolau, Jeffrey R. Snell, Shashank S. Sinha, Wayne J. Tymchak, Sean Van Diepen, David A. Morrow, Christopher F. Barnett
Journal: Journal of the American College of Cardiology (2021)
Abstract 172: Initial Rhythm and Rhythm at Moment of Transport Related to Survival in Potential ECPR Patients in the Netherlands
Authors: Corina de Graaf, Stefanie G Beesems, Rudolph W Koster
Journal: Circulation (2018)

Purpose: Extracorporeal cardiopulmonary resuscitation (ECPR) shows promising results in patients found in ventricular fibrillation (VF) without return of spontanous circulation (ROSC) on scene. Insight in rhythm at moment of transport and survival of potential ECPR patients could help to identify which patients should be transported for ECPR. Methods: Data of potential ECPR patients (shockable first rhythm, witnessed arrest, bystander CPR and age 18-70 year) transported without ROSC between 2012 and 2016 in the Amsterdam Resuscitation Study (ARREST) database were analyzed. Initial rhythm and rhythm at moment of transport was related to 30-day survival. Results: Of 5872 OHCA patients with attempted resuscitation, 649 (11%) were transported with ongoing CPR. Of these, 162 (25%) were considered potential ECPR patients and 153 cases with complete data were analysed. Thirteen of these 153 patients (9%) were alive at 30 days. At start of transport, 68 patients (44%) had VF/VT, 58 (38%) PEA and 27 (18%) asystole. Of these, 10, 2 and 1 patients survived, respectively (figure). 30-day survival of patients with a shockable rhythm at start of transport was significantly higher compared to non-shockable rhythms (15% vs 3%, p=0.014). During transport 10 of 153 patients (7%) achieved ROSC, and 3 patients (30%) survived. VF/VT at start of transport identified 10/13 (77%) of all survivors. In patients without ROSC at hospital arrival, VF/VT also resulted in the highest survival (13%). Conclusion: In ECPR candidate patients, a shockable rhythm at the moment of transport (44%) identified 77% of patients surviving 30 days.