tbuckley/cabot-search huggingface dataset:
Abstract P498: Association of Steps Per Day With Diabetes, Hypertension, and Obesity Over 10 Years: Results From the Coronary Artery Risk Development in Young Adults Study
Authors: Amanda E Paluch, Kelley Pettee Gabriel, Janet E Fulton, Juned Siddique, Kara M Whitaker, Cora E Lewis, Susan A Carlson, Pamela SCHREINER, Barbara Sternfeld, Stephen Sidney, Mercedes R Carnethon
Journal: Circulation (2020)

Introduction: Step counts are an easy way for individuals to quantify their physical activity; there is limited data relating accelerometer-derived step counts with the onset of cardiovascular risk factors. We hypothesized that steps/day are inversely associated with type 2 diabetes, stage 2 hypertension, and obesity 10 years later. Methods: Data are from 1,923 CARDIA study participants with valid (≥4 days with ≥10 hours/day) accelerometer wear (ActiGraph 7164) in 2005-2006 with at least one follow-up visit 5- or 10- years later. Multivariable Cox models calculated hazard ratios (HR) and 95% confidence intervals (CI) for incidence of type 2 diabetes, stage 2 hypertension, and obesity. Results: The analytic sample (45.3±3.6 years; 58% women, 41% black) had a mean follow-up of 9.7±1.3 years. After adjusting for demographics and lifestyle characteristics, every 1000 higher steps/day was associated with a 10% lower risk of diabetes and 5% lower risk of hypertension. When adding comorbidities to the model, the HRs were slightly attenuated, and remained significant for diabetes [0.93 (95% CI, 0.87-0.99)]. Compared to the lowest step quartile, the highest quartile was at a 43% lower risk of diabetes and a 31% lower risk of hypertension. When testing for interactions by race or sex, the only significant interaction was for sex with obesity as the outcome. Steps were only associated with obesity in women, where every 1000 higher steps/day were associated with a 13% lower risk, and the highest quartile was 61% less likely to develop obesity compared to the lowest quartile. Conclusions: Among middle age adults, accumulating a higher volume of steps/day was associated with a lower risk of type 2 diabetes and stage 2 hypertension. In women, higher steps/day was associated with lower risk of obesity. Encouraging the accumulation of steps/day may be an effective public health strategy to lower the burden of cardiovascular risk factors.
CTIM-01. GLIOBLASTOMA RE-IRRADIATION: IMPACT OF CONCOMITANT CHEMOTHERAPY
Authors: Nicolas Epaillard, Nassim Hammoudi, Matthieu Faron, Samy ammari, Johan Pallud, Guillaume Louvel, Naima Lezghed, Gabriel Garcia, Sophie Bockel, Razvan Copaciu, Edouard Dezami, Steven Knafo, Lyna Benadhou, Baptiste Abbar, Lauren Seknazi, Pamela Abdayem, Audrey Simonaggio, Kevin Bourcier, Frederic Dhermain, Sarah Dumont
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Although the standard of initial treatment is well defined for glioblastoma, no recommendation exists in the relapse setting. This work focuses on the optimal strategy for recurrent glioblastoma. METHODS Retrospective monocentric analysis of all recurrent glioblastoma adult patients treated since 2000 in one center by re-irradiation, alone or combined with chemotherapy and/or surgery at first or second relapse. RESULTS Patient (n=61) median age was 55 (27 to 76), 44% were women. At diagnosis, 77% underwent surgical resection and 23% were biopsied. Most (95%) received a Stupp regimen. After a median follow-up of 31.1 months, 44 patients (72%) had died, median overall survival (mOS) was 39.8 months. Regardless of the time of treatment, patients treated with radiotherapy concomitant to bevacizumab (RTbev) showed superior survival data compared to patients treated with radiotherapy alone (RTalone). At first relapse, median progression free survival (mPFS) of RTbev was 9.9 versus 3.6 months for RTalone (OR=3.98 (3.14–61.81); p=0.001). At second relapse, mPFS of RTbev was 9.2 versus 5.4 months for RTalone (OR=2.31 (1.18–7.75); p=0.029), and mOS of RTbev was 15.2 versus 9.1 months for RTalone (OR=3.60 (2.17–18.13); p=0.001). CONCLUSION This retrospective monocentric analysis reports a favourable impact of bevacizumab adjunction to re-irradiation.
Publisher Correction: Fast detection of SARS-CoV-2 RNA via the integration of plasmonic thermocycling and fluorescence detection in a portable device
Authors: Jiyong Cheong, Hojeong Yu, Chang Yeol Lee, Jung-uk Lee, Hyun-Jung Choi, Jae-Hyun Lee, Hakho Lee, Jinwoo Cheon
Journal: Nature Biomedical Engineering (2020)

A Correction to this paper has been published: https://doi.org/10.1038/s41551-020-00676-8.
Microglial vesicles improve post-stroke recovery by preventing immune cell senescence and favoring oligodendrogenesis
Authors: Stefano Raffaele, Paolo Gelosa, Elisabetta Bonfanti, Marta Lombardi, Laura Castiglioni, Mauro Cimino, Luigi Sironi, Maria P. Abbracchio, Claudia Verderio, Marta Fumagalli
Journal: Molecular Therapy (2020)

Contrasting myelin damage through the generation of new myelinating oligodendrocytes represents a promising approach to promote functional recovery after stroke. Here, we asked whether activation of microglia and monocyte-derived macrophages affects the regenerative process sustained by G protein-coupled receptor 17 (GPR17)-expressing oligodendrocyte precursor cells (OPCs), a subpopulation of OPCs specifically reacting to ischemic injury. GPR17-iCreERT2:CAG-eGFP reporter mice were employed to trace the fate of GPR17-expressing OPCs, labeled by the green fluorescent protein (GFP), after permanent middle cerebral artery occlusion. By microglia/macrophages pharmacological depletion studies, we show that innate immune cells favor GFP+ OPC reaction and limit myelin damage early after injury, whereas they lose their pro-resolving capacity and acquire a dystrophic "senescent-like" phenotype at later stages. Intracerebral infusion of regenerative microglia-derived extracellular vesicles (EVs) restores protective microglia/macrophages functions, limiting their senescence during the post-stroke phase, and enhances the maturation of GFP+ OPCs at lesion borders, resulting in ameliorated neurological functionality. In vitro experiments show that EV-carried transmembrane tumor necrosis factor (tmTNF) mediates the pro-differentiating effects on OPCs, with future implications for regenerative therapies.
Treatment of granuloma annulare and suppression of proinflammatory cytokine activity with tofacitinib
Authors: Alice Wang, Nur-Taz Rahman, Meaghan K. McGeary, Michael Murphy, Austin McHenry, Danielle Peterson, Marcus Bosenberg, Richard A. Flavell, Brett King, William Damsky
Journal: Journal of Allergy and Clinical Immunology (2020)
Re: J. Alfred Witjes, Harman Max Bruins, Richard Cathomas, et al. European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2020 Guidelines. Eur Urol 2020;79:82–104
Authors: Anka Baldauf, Rainer Koch, Ulrike Heberling, Christian Thomas, Michael Froehner
Journal: European Urology (2020)
AB1062 LIPODERMATOSCLEROSIS AS A TYPE OF LOBULAR PANNICULITIS: THE EFFECTIVENESS OF NON-PHARMACOLOGICAL TREATMENT METHODS
Authors: M. Sukhareva, O. Egorova, B. Belov
Journal: Annals of the Rheumatic Diseases (2020)

Background: In medical practice lobular panniculitis-lipodermatosclerosis (LDS) is becoming more and more common. It is manifested by degenerative-dystrophic changes in subcutaneous fat (SCF) and occurs more often in middle-aged women affected by chronic venous insufficiency. Objectives: to evaluate the effectiveness of mesotherapy (MT) and shockwave ultrasound therapy (UST) for LDS Methods: among 539 patients referred to the V.A. Nasonova Research Institute of Rheumatology with the referral diagnoses of erythema nodosum or panniculitis 8.5% (46) of patients (44 women, 2 men) aged 18 to 82 with overweight (32) LDS with the disease duration of 11,8±6.4 months was verified. Patients were randomized into two groups of 23 patients each: group I received daily MT (10 sessions) therapy with drugs that have antioxidant, anti-inflammatory, lymphatic drainage and lipolytic effects, and 3 MHz UST of the node area twice a week (5 sessions). In group II MT was performed daily with 9% Natrii chloridum solution at a dose comparable to group I. The control methods included general clinical examination (characterization of induration on the lower legs with an assessment of the effect of pain pressing according to visual analogue scale (VAS pain), general blood and urine tests and ultrasound with elastography (USE) of the compaction. The main stages of control: initial (T0), after 14 days (T1), 1 month (T2) and 3 months (T3). Results: before treatment 38 patients with LDS demonstrated asymmetric (83%) inflammation of SCF of the lower legs (100%) on its medial surface (91%). LDS regressed faster with normal body mass index (p = 0,04). In all patients of group I, after a course of physiotherapy a positive trend was registered, that is a decrease in VAS pain intensity (T0 50±18 mm; T1 35±11 mm), decrease in diameter (T0 6±2.2 cm; T1 4.5±1, 7 mm) and color intensity of the node (p&lt;0.002), SCF thickening which results in “lumping” with macrovascularization according to USE, and decrease in ESR and CRP. In 44% of cases the treatment effect increased to T2 (p &lt;0.05). After 3 months of observation, 15 patients required a second course of physiotherapy. In group II a positive clinical effect was registered for T2 in 14 patients (60.8%) and for T3 in 19 patients (83%) (p&lt;0.05). Over the entire observation period LDS recurrence was registered in 19 patients (41%), the median of recurrence was 3 [1; 6] months, mainly in patients of group I. Recurrence was associated with node fusion into conglomerates (OR 4.33, 95% CI 1.05-17.8; p = 0.037). MT and UST were tolerated well, no side effects were detected. Conclusion: the use of MT with 9% Natrii chloridum solution allowed us to achieve positive dynamics in patients with LDS, which significantly reduced the cost of treatment. Further studies are needed to evaluate the significance of these techniques. Disclosure of Interests: None declared
CTIM-17. PHASE I STUDY OF THE SAFETY AND IMMUNOGENICITY OF PERSONALIZED NEOANTIGEN VACCINES AND TUMOR TREATING FIELDS IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Julia Kodysh, Alex Rubinsteyn, Ana Blazquez, John Mandeli, Nina Bhardwaj, Adilia Hormigo
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Glioblastoma (GBM) generates mutation-derived tumor antigens, which arise from somatic variants that result in mutated protein fragments displayed to immune cells. These mutated proteins can provide targets for anti-tumor personalized neoantigen vaccine (PNV) therapy. Combining PNV with Tumor Treating Fields (TTFields), a modality that increases survival of GBM patients, is a viable option. METHODS In this phase I study (NCT03223103), PNV and TTFields are combined with the standard treatment for newly diagnosed GBM. Neoantigens are identified using the OpenVax computational pipeline, which identifies somatic variants in a patient’s DNA and ranks resulting neoantigens by their tumor RNA abundance and predicted HLA-I binding affinity. Each patient is vaccinated with up to 10 mutated peptides, receiving 14 doses of PNV administered subcutaneously with poly-ICLC as the adjuvant. RESULTS We report our preliminary results in the 8 patients with median age 59 (range 32–84) that have been vaccinated. Neoantigens were identified in each tumor sample in sufficient quantities for vaccination, with each vaccine comprising a median of 8.5 peptides (range 6–10). Patients received a median of 13 vaccines (range 8–14). Immune monitoring for one of the patients showed neoantigen-specific CD4 and CD8 T cell responses. There was radiological tumor progression in two while receiving PNV and in another, prior to PNV. The most common adverse events of the PNV were injection site reaction and flu-like symptoms. Combination with TTFields did not increase toxicity. The Kaplan-Meier estimated 12-month progression-free survival is 62.5% (s.e.= 17.1%) and the estimated 12-month survival from date of surgery is 83.3% (s.e.= 16.7%). The median survival has not been reached. CONCLUSIONS Despite a typically low mutational burden of GBM, selection of a sufficient number of neoantigens was successful for each patient’s vaccine. Treatment with PNV and TTFields is safe. The data is encouraging and updated results will be presented.
Inhibition of 2-hydroxyglutarate elicits metabolic reprogramming and mutant IDH1 glioma immunity in mice
Authors: Padma Kadiyala, Stephen V. Carney, Jessica C. Gauss, Maria B. Garcia-Fabiani, Santiago Haase, Mahmoud S. Alghamri, Felipe J. Núñez, Yayuan Liu, Minzhi Yu, Ayman Taher, Fernando M. Nunez, Dan Li, Marta B. Edwards, Celina G. Kleer, Henry Appelman, Yilun Sun, Lili Zhao, James J. Moon, Anna Schwendeman, Pedro R. Lowenstein, Maria G. Castro
Journal: Journal of Clinical Investigation (2020)

Mutant isocitrate dehydrogenase 1 (IDH1-R132H; mIDH1) is a hallmark of adult gliomas. Lower grade mIDH1 gliomas are classified into 2 molecular subgroups: 1p/19q codeletion/TERT-promoter mutations or inactivating mutations in α-thalassemia/mental retardation syndrome X-linked (ATRX) and TP53. This work focuses on glioma subtypes harboring mIDH1, TP53, and ATRX inactivation. IDH1-R132H is a gain-of-function mutation that converts α-ketoglutarate into 2-hydroxyglutarate (D-2HG). The role of D-2HG within the tumor microenvironment of mIDH1/mATRX/mTP53 gliomas remains unexplored. Inhibition of D-2HG, when used as monotherapy or in combination with radiation and temozolomide (IR/TMZ), led to increased median survival (MS) of mIDH1 glioma–bearing mice. Also, D-2HG inhibition elicited anti–mIDH1 glioma immunological memory. In response to D-2HG inhibition, PD-L1 expression levels on mIDH1-glioma cells increased to similar levels as observed in WT-IDH gliomas. Thus, we combined D-2HG inhibition/IR/TMZ with anti–PDL1 immune checkpoint blockade and observed complete tumor regression in 60% of mIDH1 glioma–bearing mice. This combination strategy reduced T cell exhaustion and favored the generation of memory CD8+ T cells. Our findings demonstrate that metabolic reprogramming elicits anti–mIDH1 glioma immunity, leading to increased MS and immunological memory. Our preclinical data support the testing of IDH-R132H inhibitors in combination with IR/TMZ and anti-PDL1 as targeted therapy for mIDH1/mATRX/mTP53 glioma patients.
Through-the-needle microforceps biopsy: a powerful tool but for selected patients
Authors: Stefano Francesco Crinò
Journal: Endoscopy (2020)

Pancreatic cystic lesions (PCLs) are a common incidental finding on cross-sectional imaging, with a prevalence of 13.5 % that increases with age [1]. Despite very low progression to pancreatic cancer [2], the spectrum of pathology ranges from benign lesions to invasive neoplasms, and the possible threat of cancer is a looming fear for both patients and physicians. Endoscopic ultrasound (EUS) is indicated when clinical or radiological features of concern mean the lesion is considered for surgical resection or when the patient's management dramatically changes according to the cyst histological subtype [3]. However, cyst morphology is often non-specific and "traditional" cystic fluid analyses (i. e. carcinoembryonic antigen [CEA] and cytology) obtained through EUS-guided fine-needle aspiration (EUS-FNA) have low accuracy in differentiating mucinous vs. non-mucinous lesions, and in defining the nature of the cyst [3].
22P Dynamics of indicators of the immune status in patients with metastatic solid tumours on the background of stereotactic ablative radiation therapy
Authors: A. Zozulya, I.A. Baldueva, S. Novikov, D. Girdyuk, N. Emelyanova, E. Tyuryaeva, E. Fedosova, P.E. Antipov, A. Arseniev, S. Kanaev, A. Belyaev
Journal: Annals of Oncology (2020)
PATH-01. BRAIN METASTASES FROM ENDOMETRIAL CARCINOMA: TUMOR GENETIC ALTERATIONS IN A CASE SERIES AND META-ANALYSIS
Authors: Emily Chapman, Nadejda Tsankova, Robert Sebra, Isabelle Germano
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Endometrial carcinoma (EC) is the most common gynecologic malignancy in the world. While most patients (80%) can be cured with a hysterectomy, the remaining 20% who are diagnosed with advanced or recurrent disease have worse survival rates and limited adjuvant treatment options. Discovery of novel targets and pathways is needed for better understanding of the pathogenesis and treatment development for this disease. The aim of this study is to review clinical characteristics and genetic signatures of histologically proven EC brain metastasis (BM). METHODS For the period 2000-2019 the medical records of patients with histological diagnosis of EC BM at our Institution were reviewed. Data were collected and analyzed for age, time interval between EC and EC BM diagnoses, tumor molecular and genetic signatures, and outcome. Immunohistochemistry and sequencing was performed as published. A meta-analysis was also performed for the same time period. Data presented as mean+SD and analyzed by t-test and Chi square. RESULTS There were 6 BM from 5 patients meeting our cohort entry criteria and a total 123 cases reported in the literature. The mean age was 57.6+11.7 (range 39-69) consistent with reported data. The time interval between EC and EC BM diagnoses was 145.7+119.7 (range 33.1-275.7), significantly longer than reported (19.4+27.8; range 0-156; p&amp;lt; 0.05). All BM in our cohort were metachronous, while only 59% were in the literature. Whereas all FIGO grades are reported in the literature (I=20%; II=6%; III=42%; IV=32%), only I and III were found in our cohort (I=60%, III=40%). Tumor microsatellite instability genes MSH2 and MSH6 gene were intact, whereas MLH1 and PMS2 showed mutations. PD-L1 expression was low. EC BM genomic reports were not found in the literature. CONCLUSIONS Our study brings insights on the genomic alteration burden on EC BM. Information-driven genomic testing will continue to lead patient-centered therapeutic approaches.
BIOM-37. INITIAL RADIOGRAPHIC ASSESSMENT OF ADC VALUES IN PEDIATRIC PATIENTS TREATED WITH DAY101 FOR RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMAS (LGGs) HARBORING MEK/ERK PATHWAY ALTERATIONS
Authors: Emily Krzykwa, Ronald Korn, Samuel Blackman, Karen Wright
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Calculated from a diffusion-weight image (DWI), the apparent diffusion coefficient (ADC) is a quantitative measure that reflects observed net movement of water and correlates to tumor cellularity. We examine the changes in ADC values in patients with LGG treated with dimeric, pan-RAF inhibitor DAY101 (formerly TAK-580/MLN2480). METHODS Focusing on ADC change with treatment, we reviewed historical, baseline, and on-treatment brain MRIs for 9 patients enrolled on our institutional, IRB-approved phase 1 trial of DAY101 in children and young adults with radiographically recurrent or progressive LGG harboring MEK/ERK pathway alterations. De-identified DICOM MRI files were independently reviewed. Time points selected included baseline, first follow-up and best response. The pmod molecular image software package was utilized for data processing of ADC estimates. ADC changes were displayed as a histogram with mean values. Results were based upon a single read paradigm. RESULTS A shift to lower ADC values for solid components of these tumors was observed, reflecting cellularity and organization; while necrosis correlated with a shift toward higher ADC values. DWI results show reduced ADCs in responding patients, with greater percent change in ADC from baseline associated with deeper responses among treated patients. DWI for treated patients with resultant stable disease showed no significant change in ADC values from baseline while a shift toward higher ADC values was evident in treated, progressing tumors. CONCLUSION Preliminary DWI analysis reveals that a reduction in ADC values may correlate with treatment response and a shift toward more normal cellularity in tumors treated with DAY101. This method will be applied to a larger cohort of patients in an ongoing phase 1 trial (NCT03429803) and a planned phase 2 trial.
Reverse Cardiac Remodeling Following Initiation of Sacubitril/Valsartan in Patients With Heart Failure With and Without Diabetes
Authors: Muhammad Shahzeb Khan, G. Michael Felker, Ileana L. Piña, Alexander Camacho, Devavrat Bapat, Nasrien E. Ibrahim, Alan S. Maisel, Margaret F. Prescott, Jonathan H. Ward, Scott D. Solomon, James L. Januzzi, Javed Butler
Journal: JACC Heart Failure (2020)

This study sought to determine whether patients with heart failure and reduced ejection fraction (HFrEF) with type 2 diabetes mellitus (T2DM) have similar reverse cardiac remodeling with sacubitril/valsartan as patients without T2DM.Sacubitril/valsartan promotes reverse cardiac remodeling and improves outcomes in patients with HFrEF. Patients with HFrEF with T2DM have worse prognosis than those without T2DM.In this post hoc analysis of PROVE-HF (Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure), we examined changes in N-terminal pro-b-type natriuretic peptide (NT-proBNP), measures of cardiac remodeling, and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) scores from baseline to 12 months following initiation of sacubitril/valsartan between patients with HFrEF with and without T2DM. Using latent growth curve modeling, we evaluated the longitudinal association between changes in NT-proBNP, left ventricular ejection fraction, and KCCQ-OS.Among 794 patients enrolled, 361 (45.5%) had T2DM. NT-proBNP concentrations were modestly higher at baseline among patients with T2DM but were reduced after initiation of sacubitril/valsartan. Cross-sectional improvement was observed in left ventricular ejection fraction (T2DM: 28.3% at baseline and 37% at 12 months vs. non-T2DM: 28.1% at baseline and 38.3% at 12 months) and KCCQ-OS (T2DM: 71 at baseline and 83 at 12 months vs. non-T2DM: 76 at baseline and 88 at 12 months). Similar changes were also observed for other echocardiographic measures. In longitudinal analyses, the average NT-proBNP change was similar in patients with T2DM (-5.6% vs. -7.1% per 90-day interval; p = 0.64), whereas improvements in KCCQ-OS scores were slightly smaller (2.1 vs. 3.46 per 90-day interval; p = 0.07).Sacubitril/valsartan favorably affects natriuretic peptide levels, reverse cardiac remodeling, and health status in patients with HFrEF with and without T2DM. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).