tbuckley/cabot-search huggingface dataset:
P14.12 Gyriform infiltration as imaging biomarker for adult diffuse astrocytic glioma, IDH wildtype, with molecular features of glioblastoma
Authors: E Mesny, M Barritault, C Izquierdo, D Poncet, A d’Hombres, J Guyotat, E Jouanneau, R Ameli, J Honnorat, D Meyronet, F Ducray
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Diffuse astrocytic gliomas, IDH wildtype, with molecular features of glioblastoma (molecular glioblastomas) are associated with a poor prognosis. We previously found that these tumors frequently display gyriform infiltration, defined as areas of elective cortical hypersignal on MRI FLAIR sequence. The objective of the present study was to assess the diagnostic value of gyriform infiltration as an imaging marker for these tumors. MATERIAL AND METHODS MRI scans from 430 patients with newly diagnosed glioma (molecular glioblastoma n = 31, IDH wildtype glioblastoma n = 298, IDH-mutant astrocytoma n = 50, IDH-mutant and 1p19q codeleted oligodendroglioma n= 51) were evaluated for the presence of a gyriform infiltration by 2 independent reviewers. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the performance of the presence of a gyriform infiltration for identifying molecular glioblastoma. RESULTS A gyriform infiltration was observed in 16/31 (52%) patients with a molecular glioblastoma, 40/298 (13%) patients with an IDH-wildtype glioblastoma but in none of the patients with an IDH-mutant astrocytomas or an IDH-mutant and 1p19q codeleted oligodendroglioma. Among the 56 patients with a gyriform infiltration, 54 patients had an IDH wildtype pTERT mutant glioma and 2 an IDH wildtype pTERT wildtype glioma. Interrater agreement was good (κ= 0.68, P &amp;lt; 0.001). Specificity, sensitivity, PPV and NPV of the presence of a gyriform infiltration for the diagnosis of molecular glioblastoma were 90%, 29%, 52% and 96% and for the diagnosis of an IDHwt pTERT mutant glioma were 97%, 15%, 96% and 20%. The presence of a gyriform infiltration was associated with a worse prognosis in the entire cohort (13.6 months vs 29.3 months, P = .001). CONCLUSION Gyriform infiltration is a specific imaging marker of molecular glioblastomas and IDH wildtype pTERT mutant diffuse gliomas.
The use of polyisobutylene-based polymers in ophthalmology
Authors: Leonard Pinchuk
Journal: Bioactive Materials (2021)

A novel polyolefin called poly(styrene-block-isobutylene-block-styrene) ("SIBS") originated from Joseph P. Kennedy's laboratory at the University of Akron (Akron, Ohio, United States) and was developed as a biomaterial for long-term implant applications by the author. SIBS has no cleavable groups on its backbone or sidechains, is comprised predominantly of alternating secondary and quaternary carbons on its backbone, which prevents embrittlement and cracking under flexion, and undergoes multiple purification steps which renders it extremely biocompatible and well-suited for long-term applications in the eye. This article explores two ophthalmic devices; 1) the PRESERFLO® MicroShunt (Santen Pharmaceutical Co. Ltd., Osaka, Japan) made from SIBS that lowers intraocular pressure to thwart progression of vision loss from glaucoma, and 2) a novel intraocular lens (IOL) made from crosslinked polyisobutylene, which is under-development by Xi'an Eyedeal Medical Technology Co., Ltd. (Xi'an, China) that does not glisten nor cloud over time, as do most conventional IOLs.
OCT2 pre-positioning facilitates cell fate transition and chromatin architecture changes in humoral immunity
Authors: Ashley S. Doane, Chi-Shuen Chu, Dafne Campigli Di Giammartino, Martín A. Rivas, Johannes C. Hellmuth, Yanwen Jiang, Nevin Yusufova, Alicia Alonso, Robert G. Roeder, Effie Apostolou, Ari M. Melnick, Olivier Elemento
Journal: Nature Immunology (2021)
Letter to the Editor: Postdiagnosis Aspirin Use Associated With Decreased Biliary Tract Cancer?
Authors: Hsin‐Yu Hung, Chi‐Chih Wang, James Cheng‐Chung Wei
Journal: Hepatology (2021)

Hsin‐Yu Hung and Chi‐Chih Wang contributed equally to this study. To the editor, We read with great interest the article by Liao et al.[1] revealing that postdiagnosis aspirin was associated with improved biliary tract cancer (BTC)‐specific mortality of various subtypes. We agree that the researchers collected data from the national, multicenter Cancer Registration Database and conducted a great cohort study. However, we would like to highlight some key points. First, the researchers included the BTC study group based on the International Classification of Diseases, Ninth Revision codes and the connection of national cancer registration profiles to improve the accuracy of diagnosis of BTC from these databases, and this practice is worthy of imitation in the following relevant studies. However, we suggest that the researchers should provide more detailed validation data or cite more related references to support this wonderful method in future database studies. Second, in Supporting Table S2, the researchers considered deaths from cardiovascular diseases (CVDs) as a competing risk because aspirin is frequently prescribed for patients with underlying CVDs. However, aspirin could also be prescribed for ankylosing spondylitis, osteoarthritis, systemic lupus erythematosus, and even colorectal cancer.[2,3] We suggest that the researchers should consider residual confounders during the evaluation of competing risks in the study. Finally, patients with extrahepatic cholangiocarcinoma and ampulla of Vater cancer need regular endoscopic retrograde cholangiopancreatography (ERCP) to exchange the internal drainage tube of the bile duct if an unresectable condition happened; however, therapeutic endoscopic bile duct management can be dangerous because of the bleeding risk for aspirin users.[4] This may make an important confounding factor to decrease aspirin dosage in cases that had a complicated biliary system obstruction, and the mortality risk is undoubtedly higher in these kinds of patients. We suggest that the procedure numbers of ERCP intervention should be adjusted in this excellent study. For the above reasons, we recommend that database validation and residual confounders should be considered in this study. CONFLICT OF INTEREST Nothing to report. AUTHOR CONTRIBUTIONS Manuscript preparation: Hsin‐Yu Hung, Chi‐Chih Wang, James Cheng‐Chung Wei. Critical revision: Hsin‐Yu Hung, Chi‐Chih Wang, James Cheng‐Chung Wei. All authors reviewed the manuscript and approved the final version.
Medicare Expenditures of Atezolizumab for a Withdrawn Accelerated Approved Indication
Authors: Jeromie Ballreich, Charles Bennet, Thomas J. Moore, G. Caleb Alexander
Journal: JAMA Oncology (2021)

This cross-sectional study examines atezolizumab as a second-line treatment for malignant urothelial carcinoma, which received accelerated US Food and Drug Administration approval, although the manufacturer's confirmatory trial did not identify benefits.
Older adult guidelines: What is patient reported experience across five cancer programs?
Authors: Lindsey Bandini, Christine B. Weldon, Julia R. Trosman, Sheetal Mehta Kircher, Nisha Anjali Mohindra, Al Bowen Benson
Journal: Journal of Clinical Oncology (2021)

186 Background: ASCO’s Guideline for Geriatric Oncology (Mohile SG, Et al 2018) and NCCN’s Guideline for Older Adult Oncology (v1.2021) include patient self-assessment for falls, memory/concentration, and activities of daily living. Our study collected patient reported experience with self-assessing these concerns, discussing them with clinicians, and receiving relevant referrals across adult patients with cancer. We also examined differences in reported experiences between younger and older patients. Methods: We surveyed patients 18 and over with breast, colorectal, lung or head neck cancer who received care from January 2020 to April 2021 across 5 cancer programs in Chicago: 3 academic and 2 community based. Survey included 7 items adapted from older adult oncology guidelines and associated instruments including PROMIS. Analyses used chi-square method with Yate’s correction. Results: 243 patients completed a survey, about half over and half under 65. Only 16% of patients reported that clinicians asked them about falls/walking, concentration/memory, or daily activity concerns; an additional 28% of patients brought up these concerns with clinicians (Table). Over half (51%) of all patients had at least once concern, 17% falls/walking, 30% concentration/memory and 35% daily activities. About 1/3 (35%) of patients were referred to services. Importantly, the rates of experiencing concerns associated with older adult care, initiating relevant discussions with clinicians, and receiving referrals were similar between younger and older patients (Table). Patients with concerns were more likely to get PT/OT, Geriatrics, or home health support, p =.02, p =.03, p =.04, respectively (data not shown). Conclusions: Regardless of age, half of patients reported at least one concern that is typically associated with older cancer patients. Future studies should study concerns for falls, memory, concentration, and daily activities among younger patients, with the potential to expand the guidelines accordingly. We also found gaps in identifying these concerns even within the older patient cohort, suggesting that quality improvement interventions are necessary.[Table: see text]
Humoral Immunity After mRNA SARS-CoV-2 Vaccination in Allogeneic HCT Recipients—Room for Improvement and Much to Learn
Authors: Joshua A. Hill
Journal: JAMA Network Open (2021)

Amandine Le Bourgeois, MD; Marianne Coste-Burel, PharmD; Thierry Guillaume, MD, PhD; Pierre Peterlin, MD; Alice Garnier, MD; Marie C. Béné, PharmSciD, PhD; Patrice Chevallier, MD, PhD
P13.23 Study of migration characteristics of human glioma cells in vitro
Authors: G Pavlova, S Pavlova, S Drozd, E Savchenko, L Zakharova, D Shamadykova, D Golbin, A Potapov, A Revishchin
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Gliomas are still one of the most aggressive human cancers, and even despite modern therapeutic approaches, the prognosis for patients with this disease is not favorable. It is known that glioma cells are capable of local invasiveness, when glioma cells migrate into healthy brain tissue. A lack of any definite markers, characterizing migrating glioma cells and allowing them to be distinguished from healthy brain cells, requires a thorough investigation. In case it would be possible to characterize invasive glioma cells, then a development of targeted therapy could be feasible. MATERIAL AND METHODS Cell cultures of human gliomas Gr II, III and IV were developed with 5 cultures for each Grade. MTT, RT-PCR, Western and Nosern blot, transcriptome analysis were applied. RESULTS Three cultures of human gliomas had a high degree of migration, within the range of 6% - 14%. These cultures were developed from gliomas of Grade III and Grade IV, and with IDH1- (minus) phenotype. Moreover, cell cultures with IDH1 + (plus) phenotype had a low migration rate within 1%. An intensity of migration correlated with the degree of malignancy, and an average rate decreased with a decrease of the Grade. Moreover, an analysis of the proliferative activity of cell cultures of human gliomas of various degrees of malignancy did not reveal a relationship with a migratory properties of cultures. A number of actively proliferating cultures did not show high migration, while cultures with medium proliferative activity could show a high level of migration. The low level of proliferation of cultures of gliomas of Grade II and I at the beginning of cultivation, in some cases, subsequently increased, but an inherent low migration activity did not change. In actively migrating cultures, a significant decrease in the expression of Sox2 and Nestin is detected. A positive correlation was found between migration abilities of human glioma cell culture cells and the marker Ki67, GFAP, Sox2, and Oct4. The difference was statistically significant by the one-sided Mann-Whitney test. CONCLUSION Conclusions: Cell cultures derived from glioma tumor tissue can be used to predict invasive properties of the tumor. High tumor invasiveness is characteristic for Grade III and Grade IV, and with IDH1- (minus) phenotype, and it also correlates with elevated expression of GFAP, Sox2 and Oct4The reported study was funded by RFBR according to the research project № 18-29-01012 and by the Ministry of Science and Higher Education of the Russian Federation, grant number 075-15-2020-809 (13.1902.21.0030).
Interinstitutional multidisciplinary virtual tumor board implementation for the management of breast cancer in a public health setting in Mexico.
Authors: Omar Peña-Curiel, Orestes Valles-Guerra, Karen M Velazquez-Ayala, Griselda Peña-Iturbide, Sonia Maria Flores Moreno, Jackeline Grace Lara-Campos, Martín Lara-Esqueda, Nydia Paulina Herrera-Ríos, Roberto Montes de Oca Luna
Journal: Journal of Clinical Oncology (2021)

107 Background: UNEME-DEDICAM (UD) clinics are part of a national public health initiative to provide women prompt access to cervical and breast cancer (BC) screening and diagnosis. Furthermore, UD clinics play a central role in the coordination and prioritization of patient transfer to treatment-specialized institutions. To facilitate this process, we planned and implemented an interinstitutional virtual multidisciplinary tumor board (VMDT). Herein, we present our current experience. Methods: We planned and implemented our VMDT in September 2020. Weekly sessions were established for the multidisciplinary discussion of every newly diagnosed patient at UD with a complete radiology and pathology report. Communication was accomplished through an encrypted and secure internet connection using Microsoft Teams software. VMDT members included breast pathologist, breast imaging, radio oncologist, medical oncologist, and surgical oncologist. Treatment consensus were registered in a Microsoft Word template and integrated into the medical record for each patient. Importantly, the report also included date and time for the consultation at the referral institution. Results: Between September 2020 through May 2021, 74 BC patients were diagnosed at UD. Mean age at diagnosis was 52 years. Sixty-eight patients had invasive BC, of whom early stage (I and II) accounted for 67% of patients; locally advanced (III) for 29%, and advanced (IV) for 4%. Luminal A and B type accounted for 68%; HER2+ve for 25%; and triple negative for 7%. Mean time from biopsy to complete histopathology report (biopsy-report interval) was 2.5 weeks. The mean time from VMDT consensus to patient´s first consultation at referral center (VMDT-referral interval) was 2 weeks. The mean time from biopsy to patient´s first consultation at referral center (total interval) was 5.5 weeks. Conclusions: The VMDT is a plausible strategy to streamline the inter-institutional organization for the timely care of BC patients. UD clinics play a central role in the coordination of transfer of BC patients to tertiary care centers.
Government is urged to tackle “punitive pension taxation” to stop doctors retiring early
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The BMA must push the government to remove “punitive pension taxation” that is exacerbating the medical workforce crisis by prompting many doctors to retire early or reduce their hours, doctors’ representatives have urged.

On 14 September, the BMA’s annual representative meeting unanimously (206 for; 0 against) passed a motion expressing concern that large numbers of doctors are retiring much earlier in their careers because of a combination of low …
Uncoupling vaccination from politics: a call to action
Authors: Joshua M Sharfstein, Timothy Callaghan, Richard M Carpiano, Sema K Sgaier, Noel T Brewer, Alison P Galvani, Rekha Lakshmanan, SarahAnn M McFadden, Dorit R Reiss, Daniel A Salmon, Peter J Hotez
Journal: The Lancet (2021)
P12.04 Body Mass Index: a possible PICC-related complications risk factor in neuro oncological patients
Authors: G Simonetti, P Gaviani, A Botturi, V Redaelli, E Anghileri, A Silvani
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The use of central venous catheter with peripheral insertion (PICC) has increased rapidly in recent years particularly in cancer patients because they represent a stable and safe vascular access to administer irritants or vesicants therapies. However, the benefit provided may occasionally be affected by severe complications. An observational study conducted at our Institute, showed a significant increase of thromboembolic risk in neuro-oncological patients compared to general cancer population (16.3% vs 6.7% respectively). For this reason, it is essential to identify independent risk factors in order to avoid preventable harm. MATERIAL AND METHODS Neuro-oncological patients with PICC that developed a thromboembolic event were retrospectively analyzed. We evaluated clinical data, BMI, KPS, steroid therapies and anticoagulants at the time of positioning of the PICC and at the onset of the thrombotic event. RESULTS A total of 90 neuro-oncological patients have been analyzed. The most common histology was represented by glioblastoma, followed by anaplastic astrocytoma, primary central nervous system lymphoma, grade II glioma. 17.6% of patients were at first diagnoses, 41.6% were at the first recurrence, and the remaining patients were at the second or third recurrence. The median KPS was 90 (range 80–100), and the median ECOG was 0 (range 0–2). Overall, 14% patients developed thromboembolic events within a median time of 34.5 days (range 5–146) after PICC implantation. Among these, 64% of patients was considered overweight. No patients were on anticoagulant therapy but all were treated with a median dose of 5.5 mg of steroids (range 3,5-12), stable between PICC insertion and onset of adverse event. CONCLUSION 64% of patients who developed a thromboembolic event had BMI &amp;gt;28 at the time of PICC insertion, suggesting a possible trend towards a risk of developing PICC related thrombosis in overweight/obese patients. Other independent risk factors for PICC associated complications seems to be amount of previous chemotherapies administered: 82% of patients who developed thrombotic complications had already undergone at least one line of chemotherapy before PICC placement, suggesting this condition as a possible risk factor for the onset of the event. Also failed positioning attempts could damage vascular endothelium, contributing to the onset of thrombotic complications. An accurate anamnesis and a physical evaluation with particular attention to the presence of malnutrition could help in the in the early identification of independent risk factors that could farther negatively influence the outcome of neuro-oncological patients.
Daily testing for contacts of individuals with SARS-CoV-2 infection and attendance and SARS-CoV-2 transmission in English secondary schools and colleges: an open-label, cluster-randomised trial
Authors: Bernadette C Young, David W Eyre, Saroj Kendrick, Chris White, Sylvester Smith, George Beveridge, Toby Nonnenmacher, Fegor Ichofu, Joseph Hillier, Sarah Oakley, Ian Diamond, Emma Rourke, Fiona Dawe, Ieuan Day, Lisa Davies, Paul Staite, Andrea Lacey, James McCrae, Ffion Jones, Joseph Kelly, Urszula Bankiewicz, Sarah Tunkel, Richard Ovens, David Chapman, Vineta Bhalla, Peter Marks, Nick Hicks, Tom Fowler, Susan Hopkins, Lucy Yardley, Tim E A Peto
Journal: The Lancet (2021)
In vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline
Authors: Heidi I. L. Jacobs, John A. Becker, Kenneth Kwong, Nina Engels-Domínguez, Prokopis C. Prokopiou, Kathryn V. Papp, Michael Properzi, Olivia L. Hampton, Federico d’Oleire Uquillas, Justin S. Sanchez, Dorene M. Rentz, Georges El Fakhri, Marc D. Normandin, Julie C. Price, David A. Bennett, Reisa A. Sperling, Keith A. Johnson
Journal: Science Translational Medicine (2021)

In vivo and autopsy evidence supports locus coeruleus MRI measures as proxy of initial TAU deposition and amyloid-related memory decline.
Early safety and efficacy findings of auto1 (cat19), a fast-off rate cd19 car, in relapsed / refractory indolent b cell lymphomas
Authors: C. Roddie, J. Dias, M. O'Reilly, A. C. Garai, L. Bosshard, M. Abbasian, M. Lowdell, M. Marzolini, L. Wood, G. Wheeler, J. Olejnik, L. Clifton-Hadley, B. Popova, V. Spanswick, H. Lowe, L. Ensell, J. Hartley, F. Farzaneh, D. Linch, M. Pule, K. Peggs
Journal: HemaSphere (2021)

Background: We have previously described AUTO1 (CAT19), a CD19 CAR with a fast off-rate CD19 binding domain, designed to reduce CAR T-cell immune toxicity and improve engraftment. Its clinical activity has been tested in r/r paediatric and adult B-ALL. Cumulatively, this data confirms the intended fucntion of the receptor, with low levels of CRS/ ICANS and long-term engraftment of CAR T-cells observed in both patient groups. Recently, CAR therapy has been explored in indolent lymphomas such as follicluar (FL) and mantle cell lymphoma (MCL), but a high incidence of toxicity inluding Grade 3-4 ICANS has been reported. Aims: We have initiated testing of AUTO1 (CAT19) in the setting of indolent B-cell lymphoma (NCT02935257). Methods: Manufacturing: CAR T-cell products were generated using a semi-automated closed process from non-mobilised leucapheresate. Study design: subjects>/=16y underwent lymhpodepletion with fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) followed by a single CAR T-cell infusion of 200 x10
Evaluating Serum Thymidine Kinase 1 in Patients with Hormone Receptor–Positive Metastatic Breast Cancer Receiving First-line Endocrine Therapy in the SWOG S0226 Trial
Authors: Costanza Paoletti, William E. Barlow, Erin F. Cobain, Mattias Bergqvist, Rita S. Mehta, Julie R. Gralow, Gabriel N. Hortobagyi, Kathy S. Albain, Lajos Pusztai, Priyanka Sharma, Andrew K. Godwin, Alastair M. Thompson, Daniel F. Hayes, James M. Rae
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Serum thymidine kinase 1 (sTK1) activity is associated with poor prognosis in metastatic breast cancer (MBC). We assessed the prognostic effect of sTK1 in patients with hormone receptor–positive MBC treated on a prospective randomized trial of anastrozole (A) versus A plus fulvestrant (A + F). Patients and Methods: sTK1 was assessed in 1,726 serums [baseline (BL), cycles 2, 3, 4, and 7] using the DiviTum assay. A prespecified cutoff of ≥200 Du/L was considered high. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan–Meier, log-rank tests, and Cox regression. Results: BL sTK1 was elevated in 171 (40%) of 432 patients. Patients with high versus low BL sTK1 had significantly worse PFS [median 11.2 vs. 17.3 months, HR = 1.76; 95% confidence interval (CI; 1.43–2.16); P &amp;lt; 0.0001] and OS [median 30 vs. 58 months, HR = 2.38; 95% CI (1.91–2.98); P &amp;lt; 0.0001]. OS was significantly better for patients with high sTK1 who did not have prior adjuvant tamoxifen and who received A + F versus A alone [median 46 vs. 21 months, HR = 0.58; 95% CI (0.38–0.87); P = 0.0087]. Patients with low sTK1 had no difference in outcomes by therapy (P = 0.44). At serial timepoints, high versus low sTK1 had significantly worse subsequent PFS and OS [at cycle 2: PFS HR = 1.70, 95% CI (1.34–2.17); P &amp;lt; 0.0001, OS HR = 2.51, 95% CI (1.93–3.26); P &amp;lt; 0.0001]. Conclusions: High sTK1 at BL and subsequent timepoints is associated with worse prognosis in patients with MBC starting first-line endocrine therapy (ET). Patients with low sTK1 at BL have comparable outcomes on single-agent or combination ET.