tbuckley/cabot-search huggingface dataset:
Validation of the BRODERS classifier (Benign<i>versus</i>aggRessive nODule Evaluation using Radiomic Stratification), a novel HRCT-based radiomic classifier for indeterminate pulmonary nodules
Authors: Fabien Maldonado, Cyril Varghese, Srinivasan Rajagopalan, Fenghai Duan, Aneri B. Balar, Dhairya A. Lakhani, Sanja L. Antic, Pierre P. Massion, Tucker F. Johnson, Ronald A. Karwoski, Richard A. Robb, Brian J. Bartholmai, Tobias Peikert
Journal: European Respiratory Journal (2020)

Introduction Implementation of low-dose chest computed tomography (CT) lung cancer screening and the ever-increasing use of cross-sectional imaging are resulting in the identification of many screen- and incidentally detected indeterminate pulmonary nodules. While the management of nodules with low or high pre-test probability of malignancy is relatively straightforward, those with intermediate pre-test probability commonly require advanced imaging or biopsy. Noninvasive risk stratification tools are highly desirable. Methods We previously developed the BRODERS classifier (Benign versus aggRessive nODule Evaluation using Radiomic Stratification), a conventional predictive radiomic model based on eight imaging features capturing nodule location, shape, size, texture and surface characteristics. Herein we report its external validation using a dataset of incidentally identified lung nodules (Vanderbilt University Lung Nodule Registry) in comparison to the Brock model. Area under the curve (AUC), as well as sensitivity, specificity, negative and positive predictive values were calculated. Results For the entire Vanderbilt validation set (n=170, 54% malignant), the AUC was 0.87 (95% CI 0.81–0.92) for the Brock model and 0.90 (95% CI 0.85–0.94) for the BRODERS model. Using the optimal cut-off determined by Youden's index, the sensitivity was 92.3%, the specificity was 62.0%, the positive (PPV) and negative predictive values (NPV) were 73.7% and 87.5%, respectively. For nodules with intermediate pre-test probability of malignancy, Brock score of 5–65% (n=97), the sensitivity and specificity were 94% and 46%, respectively, the PPV was 78.4% and the NPV was 79.2%. Conclusions The BRODERS radiomic predictive model performs well on an independent dataset and may facilitate the management of indeterminate pulmonary nodules.
IMMU-55. GD2 IS A MACROPHAGE CHECKPOINT MOLECULE AND COMBINED GD2/CD47 BLOCKADE RESULTS IN SYNERGISTIC EFFECTS AGAINST GD2 POSITIVE MALIGNANCIES
Authors: Johanna Theruvath, Christopher Mount, Michelle Monje, Crystal Mackall, Robbie Majzner
Journal: Neuro-Oncology (2020)

Abstract GD2 is a disialoganglioside expressed on a variety of tumors including DIPG, neuroblastoma and osteosarcoma. Anti-GD2 antibodies have demonstrated some success in neuroblastoma and they have either not proven to be effective or have not been evaluated in other GD2 positive malignancies. CD47 is the dominant “Don’t Eat Me” signal expressed by cancer cells to inhibit macrophages and blocking CD47 leads to phagocytosis of tumor cells. We hypothesized that CD47 blockade synergizes with anti-GD2. We measured in vitro phagocytosis of DIPG and NBL cells and observed a synergy of anti-GD2/CD47 compared to the single agents. In vivo, this combination led to the complete clearance of both orthotopic and metastatic models of NBL. Additionally, the combination significantly enhanced survival of OS xenografts. Finally, in a murine model of metastatic pulmonary OS, the combination led to a near elimination of all metastatic burden. To understand the underlying biologic basis, we studied the effects of GD2 crosslinking on tumor cells and the effects of GD2 blockade on macrophages. A portion of DIPG or NBL cells die when treated with dinutuximab, and those that survive upregulate surface calreticulin, an important pro-phagocytic (“Eat Me”) signal. Additionally, we have identified the ligand for GD2, a molecule expressed on macrophages known to inhibit phagocytosis. In summary, we have identified a novel combination of anti-GD2 and anti-CD47 antibodies that is highly effective in preclinical models and will soon be tested in children. Furthermore, we have shown that GD2 itself is a macrophage checkpoint or “Don’t Eat Me” signal.
ATRT-05. RESULTS OF MULTICENTER TRIAL CONCERNING THE TREATMENT OF CHILDREN WITH ATYPICAL TERATOID/RHABDOID TUMORS (ATRT) OF THE CENTRAL NERVOUS SYSTEM
Authors: Olga Zheludkova, Lyudmila Olkhova, Yuri Kushel’, Armen Melikyan, Marina Ryzhova, Alexey Kislyakov, Evgeniy Shultz, Irina Borodina, Svetlana Gorbatykh, Vladimir Popov, Marina Mushinskaya, Olga Polushkina, Eugenia Inyushkina, Natalya Yudina, Lyudmila Privalova, Lyudmila Minkina, Artem Zaichikov, Eugenia Matsekha, Ivan Fisyun, Daniil Sakun, Nadezhda Dunaeva, Vladislav Mitrofanov, Sergey Kovalenko, Ekaterina Grishina, Eduard Chulkov, Nadezhda Pishchaeva, Asmik Gevorkyan, Evgeniy Nechesnyuk, Elena Slobina, Natalya Popova, Dmitriy Pogorelov, Alexander Matitsyn, Alexander Shapochnik, Valentina Timofeeva, Andrey Korchunov, Nikolay Vorobiev
Journal: Neuro-Oncology (2020)

Abstract We analyzed 105 patients under 18 years. The median age was 21 months. There were 54 boys and 51 girls. The supratentorial tumors were in 53 patients, infratentorial in 48, and in spinal cord in 4. 60 had stage M0,29-М+and 16-Mx. All the patients got surgical treatment:total tumor removal in 34,subtotal in 37,partial in 30,and biopsy in 4;75 patients got chemoradiotherapy to ATRT-2006;6-CWS;13-EU-RHAB;5-HIT-SKK;individual schemes in 6. RESULTS: 47 are alive,1 was LFU, and 57 died. PFS was 32%±0.05; the five-year OS 40%±0.05. The median survival-30 months, the median progression-free survival-12 months, and the median of follow-up-23 months. PFS was significantly better in patients more than 12 months compared to patients younger than 12 months:40 and 12%;p=0.00161.After total resection PFS was higher compared to subtotal resection, partial resection, and tumor biopsy:48,38,0,and 0%(p=0.025). After chemoradiotherapy, PFS was higher compared to patients without radiotherapy: 49and 0%(р=0.0000000).PFS for stage M0 was higher compared to stage M+and stage Mx:41,15,and 27%,respectively(р=0.00032).PFS was better for the tumors in the spinal cord and infratentorial location compared to the supratentorial location:67,37,and 25%(p=0.0876).The survival rate was higher among the patients who got treatment according to the ATRT-2006 protocol compared to EU-RHAB, individual regimens, CWS, and HIT-SKK:39,19,17,17,and 0% respectively;p=0.00159.The survival was higher among the patients who got intraventricular/intrathecal Methotrexate,Cytarabine, Prednisolone than among the patients who got only Methotrexate or none at all:40,0,and 5%, respectively; p=0.00015. CONCLUSIONS: Survival was significantly better in patients more than 12month, without metastases, with total removal tumor, chemotheradiotherapy by ATRT-2006 protocol with i/t, i/v Methotrexate/Cytarabine/Prednisolone.
Gender-Based Differences in Outcomes Among Resuscitated Patients With Out-of-Hospital Cardiac Arrest
Authors: Purav Mody, Ambarish Pandey, Arthur S. Slutsky, Matthew W. Segar, Alex Kiss, Paul Dorian, Janet Parsons, Damon C. Scales, Valeria E. Rac, Sheldon Cheskes, Arlene S. Bierman, Beth L. Abramson, Sara Gray, Rob A. Fowler, Katie N. Dainty, Ahamed H. Idris, Laurie Morrison
Journal: Circulation (2020)

Studies examining gender-based differences in outcomes of patients experiencing out-of-hospital cardiac arrest have demonstrated that, despite a higher likelihood of return of spontaneous circulation, women do not have higher survival.Patients successfully resuscitated from out-of-hospital cardiac arrest enrolled in the CCC trial (Trial of Continuous or Interrupted Chest Compressions during CPR) were included. Hierarchical multivariable logistic regression models were constructed to evaluate the association between gender and survival after adjustment for age, gender, cardiac arrest rhythm, witnessed status, bystander cardiopulmonary resuscitation, episode location, epinephrine dose, emergency medical services response time, and duration of resuscitation. Do not resuscitate (DNR) and withdrawal of life-sustaining therapy (WLST) order status were used to assess whether differences in postresuscitation outcomes were modified by baseline prognosis. The analysis was replicated among ALPS trial (Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest) participants.Among 4875 successfully resuscitated patients, 1825 (37.4%) were women and 3050 (62.6%) were men. Women were older (67.5 versus 65.3 years), received less bystander cardiopulmonary resuscitation (49.1% versus 54.9%), and had a lower proportion of cardiac arrests that were witnessed (55.1% versus 64.5%) or had shockable rhythm (24.3% versus 44.6%, P<0.001 for all). A significantly higher proportion of women received DNR orders (35.7% versus 32.1%, P=0.009) and had WLST (32.8% versus 29.8%, P=0.03). Discharge survival was significantly lower in women (22.5% versus 36.3%, P<0.001; adjusted odds ratio, 0.78 [95% CI, 0.66-0.93]; P=0.005). The association between gender and survival to discharge was modified by DNR and WLST order status such that women had significantly reduced survival to discharge among patients who were not designated DNR (31.3% versus 49.9%, P=0.005; adjusted odds ratio, 0.74 [95% CI, 0.60-0.91]) or did not have WLST (32.3% versus 50.7%, P=0.002; adjusted odds ratio, 0.73 [95% CI, 0.60-0.89]). In contrast, no gender difference in survival was noted among patients receiving a DNR order (6.7% versus 7.4%, P=0.90) or had WLST (2.8% versus 2.4%, P=0.93). Consistent patterns of association between gender and postresuscitation outcomes were observed in the secondary cohort.Among patients resuscitated after experiencing out-of-hospital cardiac arrest, discharge survival was significantly lower in women than in men, especially among patients considered to have a favorable prognosis.
DDRE-27. LMNA-PRKDC AXIS PROMOTES CHEMORESISTANCE IN RECURRENT GBM BY STABILIZING DNA REPAIR FOCI
Authors: Miranda Saathoff, Jack Shireman, Sol Savchuk, Shivani Baisiwala, Cheol Park, Charles James, Atique Ahmed
Journal: Neuro-Oncology (2020)

Abstract Tumors in patients with recurrent GBM are resistant to standard therapies. Available models for testing experimental therapies to treat GBM are primarily derived from or representative of primary, untreated GBM. We have developed a clinically relevant model of recurrent, therapy-resistant glioblastoma (GBM6R) from a patient-derived xenograft (PDX) of primary glioblastoma (GBM6) that underwent multiple rounds of temozolomide (TMZ) treatment following intracranial engraftment in a host mouse. Initial characterizations of GBM6R revealed a significant decrease in sensitivity to TMZ both in vitro (p&amp;lt; 0.008) and in vivo (p=0.0079). An unbiased screen to identify proteins with altered expression in GBM6R, relative to treatment naïve GBM6, revealed nuclear lamina protein LMNA as highly expressed in GBM6R. From in silico analysis we found that high LMNA expression is associated with poor survival for GBM patients (p=0.0001, Gravendeel; p=0.0078, TCGA_GBM; p&amp;lt; 0.0001, CCGA; GlioVis). GBM5 and GBM43 PDX explant cultures treated with multiple doses of TMZ increased their expression of LMNA. We found that in TMZ treated and TMZ resistant tumors, that LMNA preferentially localizes to the nuclear lamina (p&amp;lt; 0.001), which is not observed in primary, untreated tumors (p&amp;lt; 0.005). Analysis of LMNA by immunoprecipitation revealed that LMNA interacts with DNA-PK and γH2AX. From these results, we hypothesize that LMNA may be acting to stabilize DNA damage foci at the nuclear periphery, which results in enhanced DNA repair. Our observations support the testing of selective DNA-PK inhibitors for treating GBM, which would inhibit TMZ-induced DNA damage repair, and enhance the cytotoxic effects of TMZ.
Covid-19: SAGE members’ interests published by government 10 months into pandemic
Authors: Rebecca Coombes
Journal: BMJ (2020)

The government has published a register listing the interests of expert members of the Scientific Advisory Group for Emergencies,1 after criticism about the group’s lack of transparency.

The BMJ highlighted the failure to disclose members’ interests last month,2 when requests for information from the government were denied or went unanswered. SAGE has been criticised for lack of openness since the start of the pandemic.3

After months of criticism …
QOL-11. COMPARISON OF TREATMENT BURDEN RATING SCALES ON NEUROCOGNITIVE OUTCOMES IN A MIXED SAMPLE OF PEDIATRIC BRAIN TUMOR SURVIVORS
Authors: Muhammad Baig, Ineke Olsthoorn, Grace Yang, Wafik Zaky, Peter Stavinoha
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Predicting neurocognitive outcomes in pediatric brain tumor (PBT) patients is challenging. Rarity of PBT makes inclusion of detailed risk factors (e.g., treatment modality, intensity, individual complications) difficult when sample sizes are small. The Neurological Predictor Scale (NPS) summarizes complications and treatment factors associated with neurocognitive risks and has modest validation. Recently, the Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) was developed to evaluate the impact of treatment intensity on psychosocial outcomes but has not been compared to neurocognitive outcomes. This study compared the NPS and PNORTI in terms of relationship to neurocognitive outcomes known to be at risk in PBT survivors. METHODS 88 PBT survivors’ neuropsychological outcomes were retrospectively analyzed in relation to the NPS and PNORTI. Variables of interest included IQ, working memory, and processing speed. RESULTS NPS associated with lower IQ (rs=-.476, p=.001), lower working memory (rs=-.323, p=.010), and lower processing speed (rs=-.389, p=.007) in patients diagnosed at a younger age, but only processing speed for children diagnosed after age 7 years (rs=-.262, p=.036). PNORTI was not correlated with neurocognitive variables for either group. CONCLUSION NPS has value in predicting neurocognitive outcomes, though much more in a younger age at diagnosis group compared to older patients. The PNORTI did not demonstrate predictive value for these neurocognitive domains in our sample. Given the potential clinical and research value of a summary rating of treatment burden relating to long-term outcome, future research should include relationship to psychosocial outcomes and quality of life.
Strain Imaging in Cardio-Oncology
Authors: Jennifer E. Liu, Ana Barac, Paaladinesh Thavendiranathan, Marielle Scherrer-Crosbie
Journal: JACC CardioOncology (2020)

Echocardiographic imaging is crucial for patient management during cardiotoxic cancer therapy. Left ventricular ejection fraction is the most commonly used parameter for identifying left ventricular dysfunction. However, it lacks sensitivity to detect subclinical changes in cardiac function due to cardiotoxic treatment. Global longitudinal strain (GLS) is the best studied strain parameter with established diagnostic and prognostic value. Multiple studies have demonstrated changes in GLS as an early marker of cardiotoxicity. This document serves as a primer to help clinicians in the acquisition and interpretation of strain in cardio-oncology. Cases with embedded videos illustrate a step-by-step approach to obtaining GLS measurements and common pitfalls to avoid. The document includes a concise summary of the indications of GLS in cardio-oncology and its role in guiding oncological therapy. Practical approaches on how to implement strain in the echo laboratory with guidance on training and quality assurance are also discussed.
Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial
Authors: Thomas Sonnweber, Sabina Sahanic, Alex Pizzini, Anna Luger, Christoph Schwabl, Bettina Sonnweber, Katharina Kurz, Sabine Koppelstätter, David Haschka, Verena Petzer, Anna Boehm, Magdalena Aichner, Piotr Tymoszuk, Daniela Lener, Markus Theurl, Almut Lorsbach-Köhler, Amra Tancevski, Anna Schapfl, Marc Schaber, Richard Hilbe, Manfred Nairz, Bernhard Puchner, Doris Hüttenberger, Christoph Tschurtschenthaler, Malte Aßhoff, Andreas Peer, Frank Hartig, Romuald Bellmann, Michael Joannidis, Can Gollmann-Tepeköylü, Johannes Holfeld, Gudrun Feuchtner, Alexander Egger, Gregor Hoermann, Andrea Schroll, Gernot Fritsche, Sophie Wildner, Rosa Bellmann-Weiler, Rudolf Kirchmair, Raimund Helbok, Helmut Prosch, Dietmar Rieder, Zlatko Trajanoski, Florian Kronenberg, Ewald Wöll, Günter Weiss, Gerlig Widmann, Judith Löffler-Ragg, Ivan Tancevski
Journal: European Respiratory Journal (2020)

Background After the 2002/2003 severe acute respiratory syndrome outbreak, 30% of survivors exhibited persisting structural pulmonary abnormalities. The long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) are yet unknown, and comprehensive clinical follow-up data are lacking. Methods In this prospective, multicentre, observational study, we systematically evaluated the cardiopulmonary damage in subjects recovering from COVID-19 at 60 and 100 days after confirmed diagnosis. We conducted a detailed questionnaire, clinical examination, laboratory testing, lung function analysis, echocardiography and thoracic low-dose computed tomography (CT). Results Data from 145 COVID-19 patients were evaluated, and 41% of all subjects exhibited persistent symptoms 100 days after COVID-19 onset, with dyspnoea being most frequent (36%). Accordingly, patients still displayed an impaired lung function, with a reduced diffusing capacity in 21% of the cohort being the most prominent finding. Cardiac impairment, including a reduced left ventricular function or signs of pulmonary hypertension, was only present in a minority of subjects. CT scans unveiled persisting lung pathologies in 63% of patients, mainly consisting of bilateral ground-glass opacities and/or reticulation in the lower lung lobes, without radiological signs of pulmonary fibrosis. Sequential follow-up evaluations at 60 and 100 days after COVID-19 onset demonstrated a vast improvement of symptoms and CT abnormalities over time. Conclusion A relevant percentage of post-COVID-19 patients presented with persisting symptoms and lung function impairment along with radiological pulmonary abnormalities &gt;100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.
IMMU-29. AIF1 IS A PROGNOSTIC BIOMARKER AND CORRELATED WITH IMMUNE INFILTRATES IN GLIOMAS
Authors: Yi Chai, Wei Liu, Junhua Wang, Libo Hu, Yuqi Zhang
Journal: Neuro-Oncology (2020)

Abstract Gliomas remain highly variable clinical behaviors, leading to emerging studies to identify prognostic factors. AIF1 (Allograft Inflammatory Factor 1) is critical for promoting both macrophage- and dendritic cells (DCs)-mediated inflammatory response and growth of vascular smooth muscle cells and T-lymphocytes. Through comparative analyses of primary LGG patients from The Cancer Genome Atlas (TCGA) dataset and Chinese Glioma Genome Atlas(CGGA) dataset, we reported that the expression level and methylation level of AIF1 gene vary among glioma patients and AIF1 expression or gene body methylation is significantly associated with glioma patient survival. Cox regression results confirmed that AIF1 played an independent predictor of survival in lower-grade glioma(LGG), with a cox coefficient of 0.251 indicating a worse prognosis. Moreover, AIF1 expression was positively correlated with infiltrating levels of CD4+ T and B cells, macrophages, neutrophils, and DCs in LGG and glioblastoma(GBM). AIF1 expression also showed strong correlations with specific immune cell markers in LGG and GBM. In addition, AIF1 expression potentially contributed to the regulation of glioma-associated macrophages and microglia. In conclusion, our findings suggested that AIF1 was correlated with prognosis and immune infiltrating levels, and it can be used as a prognostic factor in gliomas.
Pulmonary Vein Stenosis as a Pitfall of Ventilation/Perfusion SPECT/CT for Pulmonary Embolism
Authors: Felix Kind, Christian Goetz, Philipp Tobias Meyer, Daniela Föll, Maximilian Frederik Russe, Juri Ruf
Journal: Clinical Nuclear Medicine (2020)

A 58-year-old man with progressive dyspnea and recurrent extensive left-sided pleural effusion underwent pulmonary ventilation/perfusion SPECT/CT, which showed a pronounced mismatched perfusion deficit of the entire, normally ventilated left lung. As unilateral perfusion deficits of an entire lobe are generally not due to pulmonary embolism, further CT angiography and cardiac MRI were conducted. These examinations revealed high-grade left pulmonary vein stenosis (PVS) caused by pulmonary vein isolation performed for atrial fibrillation 3 and 4 years earlier. Thus, in addition to, for example, neoplastic processes or pulmonary congenital vascular abnormalities, PVS must be considered as a differential diagnosis and possible pitfall in ventilation/perfusion SPECT/CT in dyspneic patients with prior pulmonary vein isolation.
Post-Operative Atrial Fibrillation and Oxidative Stress: A Novel Causal Mechanism or Another Biochemical Epiphenomenon?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Hakan Oral
Journal: Journal of the American College of Cardiology (2008)
GCT-49. EVALUATION OF THE PERIOPERATIVE AND POSTOPERATIVE COURSE OF SURGERY OF PINEAL GERMINOMA ACCORDING TO THE SIOP CNS GCT 96 TRIAL
Authors: Ehab Shabo, Thomas Czech, James C Nicholoson, Conor Mallucci, Sevgi Sarikaya-Seiwert, Lea Guerini-Rousseau, Gianluca Piatelli, Matthew C Murray, Cecile Faure-Conter, Gabriele Calaminus
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION CNS germinoma, being marker-negative, are diagnosed by surgical biopsy. Here we evaluate the perioperative status and postoperative complications of patients with pineal germinoma who underwent a primary biopsy or resection, treated according to SIOP CNS GCT 96. METHODS 235 patients with histologically conﬁrmed germinoma were registered, of which 113 were pineal: 55 were biopsied and 58 underwent primary resection. Initial symptoms, tumour size, complications and neurological status were assessed. 111 patients were evaluable. RESULTS Pure germinoma was present in 101 patients; 10 had additional teratoma components. The main clinical symptoms at diagnosis were headache (n=98), hydrocephalus (n=93), double vision (n=62), Parinaud syndrome (n=57) and papilloedema (n=44). Tumour size was documented in 81 patients (&amp;lt;2cm, n=14; 2-3cm, n=35; ≥3cm, n=32). 17 patients underwent primary total resection, 14 subtotal resection &amp;gt;50%, 26 subtotal resection &amp;lt;50%, 39 stereotactic biopsy, 11 endoscopic biopsy, 2 open biopsy and 2 not documented. The postoperative neurological status after resection was improved in 23 patients, unchanged in 27, deteriorated in 6 and not documented in one. Clinical status after biopsy improved in 26 patients, was unchanged in 15, deteriorated in 2 and not documented in 11. Postoperatively, 16/57 patients after resection and 5/54 after biopsy developed complications (Parinaud syndrome, double vision and hydrocephalus). CONCLUSION Although surgical techniques have improved within recent decades, these results support the practice of biopsy over resection for histological confirmation of germinoma arising at the pineal site. Supported in part by German Cancer Aid.