tbuckley/cabot-search huggingface dataset:
P14.57 Association of tryptophan metabolism and depression in patients with primary brain tumors
Authors: C Juhasz, F John, S K Michelhaugh, O Muzik, G R Barger, S Mittal
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Patients with brain tumor have an increased risk for depressive disorder, whose underlying pathomechanism may involve dysregulated tryptophan/kynurenine metabolism. In this study, we analyzed the relation of depression to cerebral and systemic tryptophan metabolism in patients with primary brain tumors. MATERIAL AND METHODS Thirty-four patients with newly-diagnosed (n=19) or recurrent (n=15) primary brain tumors (25 gliomas, 8 meningiomas, 1 dysembryoplastic neuroepithelial tumor) underwent pre-treatment alpha-[11C]methyl-L-tryptophan (AMT)-PET and completed the Beck Depression Inventory-II (BDI-II) questionnaire. MRI and AMT-PET images were co-registered, and AMT K values (estimate of unidirectional tryptophan uptake, related to tryptophan metabolism) were measured in contralateral non-tumoral cortical and subcortical regions and correlated with BDI-II total and subscale (cognitive, affective, and somatic) scores. In a subset of 28 patients, plasma tryptophan metabolite levels were also measured and correlated with BDI-II scores. RESULTS In the whole group (n=34), 35% of the patients (n=12) had BDI-II scores indicating depression, while only a minority of them (n=5) were treated with selective serotonin reuptake inhibitors (SSRI). No difference was observed in AMT K values between gliomas vs. non-gliomas or between newly-diagnosed vs. recurrent tumors. Frontal cortical and thalamic AMT K values positively correlated with BDI-II total and somatic subscale scores (r=0.49, p=0.004 and r=0.53, p=0.001, respectively), and these correlations became stronger when patients with SSRI treatment were excluded. Levels of plasma tryptophan and its metabolites were not different between gliomas vs. non-gliomas, newly-diagnosed vs. recurrent tumor nor depressed vs. non-depressed patients. SSRI treatment showed no effect on plasma tryptophan metabolite levels. No correlation was found between depression and plasma tryptophan and its metabolite levels. CONCLUSION While plasma levels of tryptophan metabolites are not associated with depressive symptoms, higher tryptophan metabolism in the frontal cortex and thalamus, measured by PET, may serve as an imaging biomarker of brain tumor-associated depression and supports the role of dysregulated tryptophan/kynurenine metabolism in this condition.
A Toolbox to Characterize Human Induced Pluripotent Stem Cell–Derived Kidney Cell Types and Organoids
Authors: Jessica M. Vanslambrouck, Sean B. Wilson, Ker Sin Tan, Joanne Y.-C. Soo, Michelle Scurr, H. Siebe Spijker, Lakshi T. Starks, Amber Neilson, Xiaoxia Cui, Sanjay Jain, Melissa Helen Little, Sara E. Howden
Journal: Journal of the American Society of Nephrology (2019)

The generation of reporter lines for cell identity, lineage, and physiologic state has provided a powerful tool in advancing the dissection of mouse kidney morphogenesis at a molecular level. Although use of this approach is not an option for studying human development in vivo, its application in human induced pluripotent stem cells (iPSCs) is now feasible.We used CRISPR/Cas9 gene editing to generate ten fluorescence reporter iPSC lines designed to identify nephron progenitors, podocytes, proximal and distal nephron, and ureteric epithelium. Directed differentiation to kidney organoids was performed according to published protocols. Using immunofluorescence and live confocal microscopy, flow cytometry, and cell sorting techniques, we investigated organoid patterning and reporter expression characteristics.Each iPSC reporter line formed well patterned kidney organoids. All reporter lines showed congruence of endogenous gene and protein expression, enabling isolation and characterization of kidney cell types of interest. We also demonstrated successful application of reporter lines for time-lapse imaging and mouse transplantation experiments.We generated, validated, and applied a suite of fluorescence iPSC reporter lines for the study of morphogenesis within human kidney organoids. This fluorescent iPSC reporter toolbox enables the visualization and isolation of key populations in forming kidney organoids, facilitating a range of applications, including cellular isolation, time-lapse imaging, protocol optimization, and lineage-tracing approaches. These tools offer promise for enhancing our understanding of this model system and its correspondence with human kidney morphogenesis.
The impact of physician’s sequence [1st vs 2nd] and posture [sitting vs standing] on cancer patients’ physician preference and perception of compassion
Authors: E. Bruera, F. Strasser, G. Kaur, T. K. Zhang, L. Cohen, E. Pace, J. Palmer
Journal: Journal of Clinical Oncology (2006)

18513 Background: Our group previously found in a cross-over RCT in 69 advanced cancer patients [P] that the sitting posture was preferred; we also found that patients consistently chose the physician [MD] they observed in 2nd order [ASCO 2003:2958]. The effect of sequence on MD preference and perception of compassion had not been reported before. The purpose of this study was to assess if P preferred MD seen in 2nd order after controlling for posture. Methods: Advanced cancer P were randomized to observe 2 9-minute videos of a P/MD interaction. Both videos were identical except for the posture of the MD [sitting versus standing]. After a 2–3 minute assessment P were crossed-over into viewing the opposite video. Investigators were blinded to the type of video observed. P were blinded to the purpose of the study and difference between videos. Results: 168 P [98%] were evaluable. The mean perception of compassion [0 = worst, 50 = best] was 29 ± 13 for the 1 st MD versus 33 ± 11 for the 2 nd MD [p &lt; 0.001]. P also preferred sitting [33 ± 11] versus standing [29 ± 12, p &lt; 0.001]. The overall impression [0 = worst, 10 = best] for the MD seen 2 nd versus 1 st was 6.5 ± 2.3 versus 5.7 ± 2.7 [p ≤ 0.001]. All differences in response were independent on posture. 119/168 P [71%] perceived a difference between the 2 MDs and this difference was considered ≥ moderately important in 95 P [80%]. 76/168 P preferred the 2 nd MD [45%, 95% CI, 38–53], 38/168 P preferred the 1 st MD [23%, 95% CI, 16–29], and 54/168 P had no preference [32%, 95% CI, 25–39]. 49/114 P who expressed a preference perceived their preferred MD had spent more time with the P [43%]. 87/168 P preferred their MD to sit [52%] but they considered posture more important than time in 23 cases [20%], friendliness in 18 [15%], patience in 16 [14%], caring in 15 [14%], and respect in 18 [16%]. Conclusions: P prefer MDs they see in 2 nd order, they have an overall better impression of them and consider them more compassionate, and they perceive that they spent more time with their P, independently on the MD’s chosen posture. Most P also prefer MDs to sit but posture is rated as a relatively low priority in P/MD communication. These findings are important for clinical care and trial participation. No significant financial relationships to disclose.
CRISPR Activation Screen for Drivers of MM Cell Proliferation
Authors: Huihui Tang, Ricardo De Matos Simoes, Ryosuke Shirasaki, Olga Dashevsky, Brian Glassner, Sondra L. Downey-Kopyscinski, Sara Gandolfi, Michal Sheffer, Megan Bariteau, John G Doench, Constantine S. Mitsiades
Journal: Blood (2018)
Preemptive Therapy with Rituximab for Epstein-Barr Virus Reactivation in Children after T-Cell-Replete Haploidentical Hematopoietic Stem Cell Transplantation with Low-Dose Anti-Thymocyte Globulin
Authors: Shogo Kobayashi, Hideki Sano, Kazuhiro Mochizuki, Mitsuko Akaihata, Yoshihiro Ohara, Nobuhisa Takahashi, Hitoshi Ohto, Atsushi Kikuta
Journal: Blood (2016)
Decreasing Use of Chemotherapy in Older Patients With Stage III Colon Cancer Irrespective of Comorbidities
Authors: Viola Walter, Daniel Boakye, Janick Weberpals, Lina Jansen, Walter E. Haefeli, Uwe M. Martens, Phillip Knebel, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Chemotherapy underuse in elderly patients (aged ≥75 years) with colon cancer has been reported in previous studies. However, these studies were mostly registry-based and limited in their potential to consider underlying reasons of such undertreatment. This study aimed to evaluate patient and hospital determinants of chemotherapeutic treatment in patients with stage III colon cancer, with a particular focus on age and underlying reasons for nontreatment of elderly patients. Methods: A total of 629 patients with stage III colon cancer who were diagnosed in 2003 through 2012 and recruited into a population-based study in the Rhine-Neckar region of Germany were included. Information on sociodemographic and lifestyle factors, comorbidities, and treatment was collected from patient interviews and physicians. Patient (with an emphasis on age) and hospital factors were evaluated for their associations with administration of adjuvant chemotherapy overall and of oxaliplatin specifically using multivariable logistic regression. Results: Administration of chemotherapy decreased from 94% in patients aged 30 to 64 years to 51% in those aged ≥75 years. A very strong decline in chemotherapy use with age persisted even after comprehensive adjustment for multiple patient factors—including comorbidities—and hospital factors and was also seen among patients without any major comorbidities. Between 2005 and 2008, and 2009 and 2012, chemotherapy administration in patients aged ≥75 years decreased from 60% to 41%. Among chemotherapy recipients, old age was also strongly associated with higher odds of nonadministration of oxaliplatin. The 2 most commonly reported reasons for chemotherapy nonreceipt among the study population were patient refusal (30%) and old age (24%). Conclusions: Age was the strongest predictor of chemotherapy underuse, irrespective of comorbidities and even in patients without comorbidities. Such underuse due just to older age in otherwise healthy patients deserves increased attention in clinical practice to ensure that elderly patients also get the best possible care. Patients’ refusal as the most frequent reason for chemotherapy nonreceipt also warrants further investigation to exclude misinformation as underlying cause.
Survival outcomes following cytoreductive nephrectomy (CN) in patients with metastatic renal cell sarcomas (MRCS).
Authors: Midhun Malla, Sarah E Johnston, Yan D Zhao, Vipul Pareek
Journal: Journal of Clinical Oncology (2019)

e22519 Background: RCS are rare soft tissue sarcomas and account for 0.8-2.7% of malignant kidney tumors. Level 1 evidence guiding optimal patient management is lacking due to the rarity of this disease. Utilizing the NCDB, we analyzed prognostic factors, the current treatment patterns and outcomes in patients with RCS in the United States. Methods: The NCDB was queried from 2004- 2015 for patients diagnosed with MRCS. Baseline patient characteristics were summarized using descriptive statistics. Impact of baseline demographic, Clinicopathologic variables and treatment on overall survival (OS) was evaluated using univariate (UV) and multivariable (MV) cox proportional hazards analysis. Results: 454 patients diagnosed with MRCS between 2004- 2015 were included in this analysis. Median age at diagnosis was 63. Males (62%) had higher incidence of RCS compared with females. 86% (n = 389) were Caucasian, while only 9.5% (n = 43) were African American. Right and left kidneys were equally affected. Spindle cell sarcoma was the most common histology (n = 276). 37.5% (n = 170) underwent CN. 49% of patients received chemotherapy (n = 216) and 24% received radiation therapy (n = 109). Overall, 48% (n = 82) of patients who underwent nephrectomy had chemotherapy. Median OS was 4.5 months (3.8-5.2 mos.). On UV analysis age ≥ 55 years (HR: 1.92, p &lt; 0.001), no systemic treatment (HR: 1.91, P &lt; 0.01), and no CN (HR: 2.1, p &lt; .001) had worse OS. On MV analysis, patients who did not undergo CN had significantly worsened OS compared to CN (7.56 vs 3.35 mos., HR-1.91, CI: 1.52- 2.41 p &lt; 0.001). Patients who received chemotherapy after CN had a better OS (13.3 vs 3.7 mos., p &lt; 0.001). Conclusions: MRCS is an aggressive malignancy with a median OS of less than 5 months. Age at diagnosis, CN and systemic therapy had a statistically significant impact on OS. Given the rarity of the tumor and inadequacy of guidelines, these results can be considered in making management decisions. We understand the limitations of a registry-based study and hence, prospective multi-national clinical trials are essential to further guide us on management of this rare tumor. [Table: see text]
P11.30 Special VEGF90kDa form in exosome from GBM cells activates TAZ in endothelial cells to promote angiogenesis and contributes bevacizumab resistance
Authors: Z Wang, Y Yuan, C Xu, Y Liu
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma (GBM) has obvious blood vessels proliferation, which is one of the important histological diagnostic criteria. Bevacizumab, VEGF targeted inhibitor, is found inefficient in 2/3 cases after the clinical trial. Here, we found a specific 90kDa form of VEGF (VEGF90K) in exosomes of GBM could activate TAZ expression in endothelial cells to promote angiogenesis, which might also contribute to Bevacizumab treatment resistance. MATERIAL AND METHODS Exosomes were isolated from U87, LN229 GBM cell culture medium and characterized using transmission electron microscopy, nanoparticle analysis, and western blotting. VEGF expression in GBM and TAZ expression in human umbilical vein endothelial cells (HUVEC) are inhibited by shRNA. In vitro migration, proliferation, and tube formation assays were used to assess the angiogenic potential of HUVEC cells. Western blotting was used to analysis TAZ expression in HUVEC. Bevacizumab or exosome inhibitor GW4869 were used separately or together to evaluation their blocking effects on angiogenic functions of GBM cells. RESULTS we found a unique 90kDa form of VEGF (VEGF90K) from exosome of GBM cells could activate TAZ expression in HUVEC cells which correlated with higher levels of cellular migration, proliferation, and tube formation. Knockdown VEGF expression in GBM exosomes or TAZ expression in HUVEC cells could decrease the angiogenic function of GBM cells. GW4869 combine Bevacizumab had significantly inhibited the angiogenic ability of GBM cells in vivo and in vitro. CONCLUSION A specific exosome-associated VEGF from GBM can promote angiogenesis by activating TAZ expression in endothelial cells. Targeted inhibition of exosome secretion can significantly inhibit tumor angiogenesis and restore bevacizumab effect. Our study highlights the unique properties of VEGF in exosome which might help to explore new treatment strategies of GBM.
OS7.6 Socioeconomic burden and associations with quality of life in meningioma patients
Authors: H Wirsching, C Morel, P Roth, M Weller
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Socioeconomics affect the outcome of neurological patients, but the socioeconomic burden of brain tumors has not been studied in detail. PATIENTS AND METHODS This survey study in a clinically well-annotated cohort of meningioma patients was designed to explore socioeconomic status parameters at diagnosis and one year thereafter. The survey comprised level of education, profession, employment status, subjective work ability, monthly income and the EPICES social deprivation score. Quality of life (QoL) and symptom burden were queried utilizing the EORTC-QLQ-C30/BN20 and MDASI-BT. A multivariate binary regression model was applied to explore associations of socioeconomics with QoL. RESULTS Completed surveys were obtained from 249 of 410 patients (61%) who were invited to participate. The level of education was an apprenticeship or higher in 214 patients (86%). One year after diagnosis, there was a 20% decline in the fraction of employed patients and a more than twofold increase in unemployment and disability (p&lt;0.001). There was a decrease in monthly income among patients with a baseline income below national average (p=0.008). On multivariate analyses, there was an association of inferior QoL with pre-operative unemployment or retirement (OR 2.43, 95% CI 1.02–5.88), whereas a subjective work ability of &gt;70% was associated with better QoL (OR 0.37, 95% CI 0.15–0.92). CONCLUSION Socioeconomics assessments should be incorporated in prospective neuro-oncology clinical trials. A more detailed knowledge of the effects of socioeconomics on patient outcome will aid in identifying patients at risk for deterioration and allow to implement improved preventive and supportive strategies.
Clinical outcomes and prognostic factors of 582 nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.
Authors: Jin Yi Lang, Weidong Wang, Peng Xu
Journal: Journal of Clinical Oncology (2012)

5597 Background: To evaluate the 5-yrs clinical outcomes and prognostic factors of 582 nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). Methods: 582 NPC patients primarily treated with IMRT in Sichuan Cancer Hospital from Jan.2001 to Dec.2004 were analyzed retrospectively, including 460 males and 122 females. The prescription dose was delivered as follows: gross target volume (GTVnx) 67-76Gy in 30-33 fractions, positive neck lymph nodes (GTVln-R/L) 60-70Gy in 30-33 fractions, The lower neck and the supraclavicular fossae were irradiated with the conventional 2D technique using an anterior field. The Kaplan-Meier method was used to calculate the local-regional control rate (LRC) and overall survival rate (OS). Acute and late toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria, meanwhile analyze the prognostic factors. Results: The median follow-up interval was 66.4 months. The 5-year local control, regional control, distant metastasis-free survival, disease free survival, disease specific survival and overall survival rate was 89.8%, 95.2%, 74.1%, 69.6%, 83.2% and 77.1%. 133 patients died during the follow-up. The 5-year DMFS of IMRT and IMRT combined with chemotherapy was 62.1% and 70.9%, the OS of them was 75.9% and 79.1%. The incidence of grade 3 acute and late toxicity was 38.3% and 4.2% respectively.Univariate analysis revealed that gender, T/N stage, clinical stage, radiotherapy interruption, anemia and weight loss was the significant prognostic factor for the OS. Multivariate analysis showed that N stage, radiotherapy interruption, chemotherapy, the volume of GTVnx, age, anemia and weight loss was the independent prognostic factors for the OS. Conclusions: The 5-year local control and overall survival rate of NPC treating with IMRT was 89.8% and 77.1%. The clinical stage, N stage , volume of GTVnx and chemotherapy was the main prognostic factor for the OS. The acute and late toxicities were mainly grade I and II. Distant metastasis was the main pattern of failure.
Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study
Authors: Salim Yusuf, Philip Joseph, Sumathy Rangarajan, Shofiqul Islam, Andrew Mente, Perry Hystad, Michael Brauer, Vellappillil Raman Kutty, Rajeev Gupta, Andreas Wielgosz, Khalid F AlHabib, Antonio Dans, Patricio Lopez-Jaramillo, Alvaro Avezum, Fernando Lanas, Aytekin Oguz, Iolanthe M Kruger, Rafael Diaz, Khalid Yusoff, Prem Mony, Jephat Chifamba, Karen Yeates, Roya Kelishadi, Afzalhussein Yusufali, Rasha Khatib, Omar Rahman, Katarzyna Zatonska, Romaina Iqbal, Li Wei, Hu Bo, Annika Rosengren, Manmeet Kaur, Viswanathan Mohan, Scott A Lear, Koon K Teo, Darryl Leong, Martin O'Donnell, Martin McKee, Gilles Dagenais
Journal: The Lancet (2019)
PDGFR and c-Kit as therapeutic targets and p53 and ki67 as prognostic markers for low-grade endometrial stromal sarcoma.
Authors: Jeong-Yeol Park, Jong-Hyeok Kim, Kyu-Rae Kim, Joo-Hyun Nam
Journal: Journal of Clinical Oncology (2012)

e15559 Background: To determine whether proteins targeted by currently available targeted agents are expressed in low-grade endometrial stromal sarcoma (LGESS) and to test these can be prognostic markers for LGESS. Methods: Of 48 patients with LGESS, 39 patients whose paraffin blocks of tumor in hysterectomy specimen were available were included. Using tissue microarrays, immunohistochemical expression of five therapeutic targets (EGFR, HER-2/neu, VEGFR, PDGFR and c-kit), and three proteins involved in cell proliferation (p16, p53, and ki67) were investigated. The association of these targets and markers with other clinopathologic factors and disease-free (DFS) and overall survival (OS) were analyzed. Results: EGFR and HER-2/neu were not expressed in 39 patients. VEGFR, PDGFR, c-kit, p16, p53, and ki67 was expressed in 10 (25.6%), 28 (71.8%), 32 (82.1%), 18 (46.2%), 4 (10.3%), and 21 (53.8%) patients, respectively. Expression of each marker was not significantly associated with other clinicopathologic factors. In multivariate analysis, p53 and ki67 were associated with significantly poorer DFS and OS. The 5-year DFS was 88%, 46% and 0% for p53(-)/ki67(-) group (n=18), p53(-)/ki67(+) group (n=17), and p53(+)/ki67(+) group (n=4), and the 5-year OS was 100%, 71%, and 0%, respectively. The time interval to recurrence was longer and more patients had distant recurrence in p53(+)/ki67(+) group. Conclusions: In patients with LGESS, c-kit and PDGFR were expressed in high portion of patients, suggesting imatinib mesylate may be a potential target agent. Both p53 and ki67 had strong prognostic implication, suggesting the combination of these proteins may be used as a prognostic marker.
Inhaled corticosteroids and pneumonia mortality in COPD patients
Authors: Samy Suissa
Journal: European Respiratory Journal (2019)

<b>The "paradoxical" effect of inhaled corticosteroids increasing pneumonia incidence in COPD but reducing post-pneumonia and all-cause mortality is no paradox but due to selection and immortal time biases in the observational studies of mortality</b>http://bit.ly/2Yd3hDh
Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial
Authors: Giancarlo Comi, Ludwig Kappos, Krzysztof W Selmaj, Amit Bar-Or, Douglas L Arnold, Lawrence Steinman, Hans-Peter Hartung, Xavier Montalban, Eva Kubala Havrdová, Bruce A C Cree, James K Sheffield, Neil Minton, Kartik Raghupathi, Ning Ding, Jeffrey A Cohen
Journal: The Lancet Neurology (2019)