tbuckley/cabot-search huggingface dataset:
Sustained Release of Dexamethasone from Sulfobutyl Ether β‐cyclodextrin Modified Self‐Assembling Peptide Nanoscaffolds in a Perinatal Rat Model of Hypoxia–Ischemia
Authors: Lei Lu, Edward A. Armstrong, Jerome Y. Yager, Larry D. Unsworth
Journal: Advanced Healthcare Materials (2019)

Inflammation plays a critical role in the development of hypoxia-ischemia (HI) induced newborn brain damage. A localized, sustained delivery of dexamethasone (Dex) through an intracerebral injection could reduce the inflammatory response in the injured perinatal brain while avoiding unnecessary side effects. Herein, investigated using anionic sulfobutyl ether β-cyclodextrin (SBE-β-CD) to load Dex in the (RADA)4 nanofiber networks as a means of reducing the inflammatory response to HI injury is investigated. The ionic interaction between SBE-β-CD and (RADA)4 dramatically affects nanofiber formation and the stability of the nanoscaffold is highly dependent on the SBE-β-CD/(RADA)4 ratio. It is observed that the Dex release rate is affected by the concentration of SBE-β-CD and (RADA)4 peptide. A higher concentration of SBE-β-CD or (RADA)4 results in a higher drug encapsulation efficiency and slower release rate of Dex. This phenomenon may be related to the structure of fiber bundles. Animal studies show that nanoscaffold loaded with Dex inhibits both microglia activation and glial scar formation compared to controls (Dex alone or nanoscaffold alone) within 2 days of injury. It is thought that this is a step toward building a multifaceted nanoscaffold that can be used to treat HI events in perinates.
Association of Leukemia Cutis With Survival in Acute Myeloid Leukemia
Authors: Cynthia X. Wang, Iskra Pusic, Milan J. Anadkat
Journal: JAMA Dermatology (2019)

Leukemia cutis (LC) is an important yet understudied extramedullary manifestation of leukemia. Previous reports have suggested poor prognosis for patients with LC, but these reports have largely consisted of descriptive studies with a limited number of patients.To identify patient factors associated with LC and characterize the association of LC with the course of acute myeloid leukemia (AML).This retrospective, matched-cohort study included 1683 patients with AML diagnosed from January 1, 2005, to April 1, 2017, with and without biopsy-proven LC seen at a single-center, tertiary care hospital in St Louis, Missouri. To specifically evaluate differences in survival, propensity scoring was used to match patients with AML with LC to patients with AML without LC off the logit of propensity score based on age, race/ethnicity, sex, and leukemia type. Kaplan-Meier methods were used to compare cumulative probability survival. Matched survival analysis was performed with extended Cox regression to determine factors associated with leukemia-specific and overall survival.Leukemia-specific survival and overall survival.A total of 1683 patients were reviewed, including 78 patients with biopsy-proven LC of the AML type and 1605 patients with AML without LC. A total of 62 of the patients with AML and LC (mean [SD] age, 58.2 [11.7] years; 33 [53.2%] male) were matched in a 1:3 ratio to 186 patients with AML without LC (mean [SD] age, 58.2 [13.5] years; 103 [55.4%] male). The 5-year survival among the 62 patients with AML with LC was 8.6%, shorter than the 28.3% among the 186 matched patients with AML without LC. Matched survival analysis revealed that patients with AML and LC compared with those without LC had hazard ratios of 2.06 (95% CI, 1.26-3.38; P = .004) for leukemia-specific death and of 1.66 (95% CI, 1.06-2.60; P = .03) for all-cause death. In addition, matched patients with LC had greater odds of extramedullary organ burden (odds ratio, 3.48; 95% CI, 1.72-7.05; P < .001).The results suggest that the presentation of LC in patients with AML is associated with decreased overall survival and leukemia-specific survival. Patients with AML presenting with LC may require more intensive treatment and monitoring of their leukemic disease.
PS-075-AAV-delivered IL-21 activates CD8+ T-cells to clear HBV replicon plasmid and cccDNA in mice
Authors: Zhongliang Shen, Jing Liu, Jingwen Wu, Yuanfei Zhu, Gaiyun Li, Jun Wang, Mengjun Luo, Qiang Deng, Jiming Zhang, Youhua Xie
Journal: Journal of Hepatology (2019)
Abstract BS1-2: Neutrophil extracellular traps promote breast cancer metastasis
Authors: M Egeblad
Journal: Cancer Research (2019)

Abstract Cancer cells from a primary tumor can disseminate to other tissues, but remain dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to “awaken”, resume proliferation, and develop into metastases. Using mouse models, we have found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Using intravital imaging techniques, which allow for long-term time-lapse imaging of cancer cells and surrounding host cells in living mice, we observed that sustained inflammation induced the formation of neutrophil extracellular traps (NETs). NETs are pathogen-trapping structures generated by expulsion of the neutrophil's DNA with associated proteolytic enzymes in response to e.g., infections. We confirmed that NETs were present in clinical samples of breast cancer lung metastases. Mechanistic analysis revealed that NETs were required for awakening dormant cancer and specifically that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin alpha-3 beta-1 signaling. We generated antibodies against NET-remodeled laminin and these prevented awakening of dormant cells in mice. In addition, pharmacological inhibition of NET formation or digestion of NETs with DNase I-coated nanoparticles also markedly reduced awakening and lung metastases in mice. Our data suggest that induction of NETs is an important host-mediated mechanism of promoting metastasis and a potential therapeutic target to prevent preventing dormant cell awakening and prolong the survival of cancer patients. Citation Format: Egeblad M. Neutrophil extracellular traps promote breast cancer metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr BS1-2.
Review: In adults with AF and HF, AF catheter ablation vs drug therapy reduces mortality and HF hospitalizations
Authors: Manoj N. Obeyesekere
Journal: Annals of Internal Medicine (2019)

Source Citation Turagam MK, Garg J, Whang W, et al. Catheter ablation of atrial fibrillation in patients with heart failure: a meta-analysis of randomized controlled trials. Ann Intern Med. 2018. [Epub ahead of print]. 30583296
FRI-107-Emerging role of taurine conjugated bile acids in the gut liver axis and on hepatic bile acid receptors in chronic hepatitis C
Authors: Rabab Oun Ali Anwar Ali, Gabriella quinn, kareen hill, Grace Zhang, Christopher Koh, Elliot Levy, David E Kleiner, Ohad Etzion, Theo Heller
Journal: Journal of Hepatology (2019)
Complement therapeutics meets nanomedicine: overcoming human complement activation and leukocyte uptake of nanomedicines with soluble domains of CD55
Authors: Geoffrey Gifford, Vivian P. Vu, Nirmal K. Banda, V. Michael Holers, Guankui Wang, Ernest V. Groman, Donald Backos, Robert Scheinman, S. Moein Moghimi, Dmitri Simberg
Journal: Journal of Controlled Release (2019)
Abstract 17206: Prognostic Impact of Cardio-renal Anemia Syndrome in Acute Decompensated Heart Failure With Preserved and Reduced Ejection Fraction; An Analysis From Mode of Death
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Jun Nakamura, Makoto Abe, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami
Journal: Circulation (2017)

Backgrounds: Cardio-renal anemia syndrome (CRAS) has the prognostic significance in patients (pts) with heart failure. There is a difference in mode of death (cardiac [sudden vs pump failure death] vs non-cardiac death) between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF). However, there is no information available on the different impact of CRAS in the prediction of mode of death in pts with acute decompensated heart failure (ADHF), relating to HFpEF and HFrEF. Methods and Results: We studied 303 pts admitted for ADHF and discharged with survival (HFpEF(LVEF≥50%);n=140, HFrEF(LVEF<50%); n=163). As an index of CRAS at the admission, we proposed a new variable : product of creatinine (Cr) and blood urea nitrogen (BUN) divided by hemoglobin (Hb), CrхBUN/Hb. During a follow-up period of 5.1±4.3 yrs, 65 pts had cardiac death (sudden cardiac death in 37 and pump failure death in 27 pts) and 56 pts had non-cardiac death. CrхBUN/Hb was significantly associated with cardiac death, wh...
Rapid histology of laryngeal squamous cell carcinoma with deep-learning based stimulated Raman scattering microscopy
Authors: Lili Zhang, Yongzheng Wu, Bin Zheng, Lizhong Su, Yuan Chen, Shuang Ma, Qinqin Hu, Xiang Zou, Lie Yao, Yinlong Yang, Liang Chen, Ying Mao, Yan Chen, Minbiao Ji
Journal: Theranostics (2019)

Maximal resection of tumor while preserving the adjacent healthy tissue is particularly important for larynx surgery, hence precise and rapid intraoperative histology of laryngeal tissue is crucial for providing optimal surgical outcomes. We hypothesized that deep-learning based stimulated Raman scattering (SRS) microscopy could provide automated and accurate diagnosis of laryngeal squamous cell carcinoma on fresh, unprocessed surgical specimens without fixation, sectioning or staining. Methods: We first compared 80 pairs of adjacent frozen sections imaged with SRS and standard hematoxylin and eosin histology to evaluate their concordance. We then applied SRS imaging on fresh surgical tissues from 45 patients to reveal key diagnostic features, based on which we have constructed a deep learning based model to generate automated histologic results. 18,750 SRS fields of views were used to train and cross-validate our 34-layered residual convolutional neural network, which was used to classify 33 untrained fresh larynx surgical samples into normal and neoplasia. Furthermore, we simulated intraoperative evaluation of resection margins on totally removed larynxes. Results: We demonstrated near-perfect diagnostic concordance (Cohen's kappa, κ > 0.90) between SRS and standard histology as evaluated by three pathologists. And deep-learning based SRS correctly classified 33 independent surgical specimens with 100% accuracy. We also demonstrated that our method could identify tissue neoplasia at the simulated resection margins that appear grossly normal with naked eyes. Conclusion: Our results indicated that SRS histology integrated with deep learning algorithm provides potential for delivering rapid intraoperative diagnosis that could aid the surgical management of laryngeal cancer.
FRI-367-Pre-liver transplant profile of cardiovascular risk factors and its impact on early post-transplant outcome
Authors: Silvia Martini, Alessandra Risso, Elena Mosso, Federica Calvo, Claudia Chialà, Francesco Tandoi, Walter Grosso Marra, Angelo Panio, Antonio Ottobrelli, Giorgio Maria Saracco, Renato Romagnoli, Bruna Lavezzo
Journal: Journal of Hepatology (2019)
PS-137-A multicentric study on real-life impact of nivolumab in patients with hepatocellular carcinoma
Authors: Leonardo Gomes da Fonseca, Beatriz Minguez, Christie Perelló, Manuel de la Torre, Laura Márquez, Antonio Guerrero Garcia, Maria Torner Simó, Mónica Pons, José Luis Calleja Panero, Bruno Sangro, Ana M Matilla, José Luis Lledó, Maria Varela, Jordi Rimola, Jordi Bruix, Maria Reig
Journal: Journal of Hepatology (2019)
The genomic landscape of anaplastic Wilms tumors with diffuse versus focal anaplasia.
Authors: Gabriel G Malouf, Linda Dainese, Xiaoping Su, Arnauld Verschuur, Christophe Bergeron, Roger Mouawad, Annick Blaise, Yves Le Bouc, David Khayat, Aurore Coulomb
Journal: Journal of Clinical Oncology (2015)

10062 Background: Anaplasia is a potent marker for adverse outcome in patients with Wilms tumors (WT). While WT patients with focal anaplasia (FA) have similar survival to those with nonanaplastic intermediate risk WT, patients with diffuse anaplasia (DA) display poor outcomes. Beside TP53 mutations, the genome-wide genetic basis of WT remains unknown. Methods: We performed whole-exome sequencing on genomic DNA derived from 11 WT and matched normal DNA from the same patients, using Agilent human V5 (51Mb) capture and the HiSeq sequencing platform. Overall, 8 and 3 matched pairs with DA and FA were assessed, respectively. Paired-end RNAseq was also performed in the same dataset for fusion transcript detection. Chromosome 17p copy number, where TP53 is located, was assessed by a MLPA assay. Results: Overall, we identified 117 (median 10, range 5-25) non-synonymous somatic single nucleotide variants, of which 47 were predicted to lead to a deleterious protein. No difference was observed in term of total number of mutations between WT with DA and FA, respectively. TP53 mutations were identified in 4 DAWT. In addition, 2 DAWT and 2 FAWT harbored identical hotspot DROSHA mutation (E1147K). Ingenuity Pathway Analysis revealed enrichment for mutations in genes involved in embryonal tumor development (ARMCX3, BCOR, FLT4, KMT2C, REST and TP53) (p = 2.7x10-4). All but one case of DAWT with TP53 mutations harbored TP53 deletion; the case without TP53 deletion had in addition DROSHA mutation. The 4 patients with TP53 mutations died as compared to one out of 7 without mutation (p = 0.01). No known or novel fusion transcripts were identified. Conclusions: Our results reveal an exceptionally low mutational load in anaplastic WT, consistent with previously reported results in pediatric solid tumors. DROSHA and TP53 are likely to be mutually exclusive mutations in WT. Updated results with an independent validation dataset will be presented at the meeting.
Healthcare plan and provider ratings among cancer survivors.
Authors: Michael T. Halpern, Matthew Urato, Margot Schwartz, Erin E. Kent
Journal: Journal of Clinical Oncology (2015)

9579 Background: Providing optimal healthcare for cancer survivors is important to address symptoms from cancer and cancer treatment, reduce risks of subsequent cancers, and improve quality of life. However, little is known about patient-level factors influencing ratings of healthcare plans or providers by survivors. Methods: This study used ratings provided by cancer survivors in the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare Survey linked to data from NCI’s Surveillance, Epidemiology, and End Results (SEER) Program (SEER-CAHPS). CAHPS data on self-reported general and mental health status and three rating categories (overall care [OC], physician [MD], and healthcare plan [HP]) were linked to SEER data on patient sociodemographics and cancer characteristics. Medicare beneficiaries diagnosed with cancer in SEER regions 1997-2011 who participated in the CAHPS Medicare Survey at least one year after cancer diagnosis were included. The study included only individuals alive at least one year following CAHPS survey completion, age >66, and diagnosed with non-metastatic breast, colorectal, lung, or prostate cancer. Results: We identified 23,969 cancer survivors with linked SEER-CAHPS data. Higher self-rated general health was largely associated with higher ratings for OC, MD, and HP for all four included cancer types. However, other factors significantly associated with ratings tended to differ by both rating category and cancer type (see table). Time since diagnosis and type of Medicare plan (FFS vs. HMO) were not significantly associated with any ratings. Conclusions: Beyond self-rated general health, survivor characteristics predicting higher ratings varied substantially by cancer and rating type. These results suggest that the experience of care among cancer survivors is diverse and is significantly influenced by their cancer type. Efforts to improve care for cancer survivors will need to be tailored for each survivor group. Significant (p<0.01) predictors of higher (+) or lower (-) CAHPS ratings. Breast Colorectal Lung Prostate OC MD HP OC MD HP OC MD HP OC MD HP Higher Mental Health + + + + + Older Age + + + + Asian - Black + + Hispanic + + College Graduate - - - - - - Stage 2/3 at Dx + + + Yrs Since Dx FFS healthplan
Diffuse Subcutaneous Emphysema
Authors: Tiffany M St Clair, Eric Zwemer
Journal: New England Journal of Medicine (2019)

A 14-year-old boy was admitted with a severe asthma exacerbation. A chest radiograph showed pneumomediastinum with diffuse subcutaneous emphysema. As his respiratory status improved, swelling and palpable crepitus developed in both cheeks and the right eyelid.
Association of Anti–Programmed Cell Death 1 Cutaneous Toxic Effects With Outcomes in Patients With Advanced Melanoma
Authors: Henry T. Quach, Anna K. Dewan, Elizabeth J. Davis, Kristin K. Ancell, Run Fan, Fei Ye, Douglas B. Johnson
Journal: JAMA Oncology (2019)

This cohort study of patients with advanced melanoma treated with anti–programmed cell death 1 with or without ipilimumab assessed whether cutaneous toxic effects were associated with superior clinical outcomes.
Long-term outcomes of rituximab use prior to autologous stem cell transplant (ASCT) in low-grade follicular lymphoma (FL) at the time of first progression.
Authors: Roberto Antonio Ferro, Vijaya Raj Bhatt, Lynette Smith, Matthew Alexander Lunning, Philip Jay Bierman, James O. Armitage, Gregory Bociek, Julie Vose
Journal: Journal of Clinical Oncology (2015)

7036 Background: Some studies suggest that prior use of rituximab is associated with poor outcomes following ASCT in relapsed diffuse large B-cell lymphoma (DLBCL). The effects of rituximab use prior to ASCT on long-term outcomes of FL are unclear. Rituximab in addition to ASCT has been associated with an increased risk of secondary primary malignancy (SPM) especially of solid tumors; however, this study included all lymphoma subtypes (J Clin Oncol 29:814-824, 2011). Methods: This is a retrospective study of 84 low grade FL patients treated by the Nebraska Lymphoma Study Groupbetween 1987-2013. We used the Chi-square or Fisher’s exact tests to compare characteristics of patients who did vs. did not receive rituximab before ASCT. The Kaplan-Meier method was used to estimate overall survival (OS) and event-free survival (EFS). Results: 34 patients (40%) received rituximab prior to ASCT. Rituximab vs. no-rituximab groups were similar in sex distribution (males 74% vs. 54%, p = 0.07), more likely to be older (mean age of 51 vs. 44 years, p = 0.0004), have received 3 or more prior chemotherapy regimens (53% vs. 24%, p = 0.004) and less likely to have received total body irradiation (TBI) (3% vs. 74%, p < 0.0001). Rituximab group was more likely to be at second complete remission (53% vs. 14%, p = 0.0004) prior to ASCT. At a median follow-up of 10.2 years, 41 patients (49%) died. The 10-year EFS was similar (49% vs. 32%, p = 0.10) but the 10-year OS was better in the rituximab group (74% vs. 46%, p = 0.009). The risk of SPM (excluding non-melanoma skin cancers) was similar in the groups with or without rituximab (18% vs. 12%, p = 0.21). Conclusions: Within the limitations of this study, rituximab use prior to ASCT resulted in similar EFS but improved OS. In addition, we did not find an increased risk of SPM with rituximab use prior to ASCT. Patients who received rituximab prior to ASCT (performed at the time of first progression) have an OS of 74% at 10 years post-ASCT. Rituximab use prior to ASCT does not influence outcomes of subsequent ASCT in FL as it appears to do in DLBCL. The current study confirms that ASCT remains an excellent salvage option for patients previously treated with immunochemotherapy.
Assessment of the external validity of National Comprehensive Cancer Network and European Society for Medical Oncology Guidelines for Non-Small Cell Lung Cancer in a population of elderly patients aged 80 and older.
Authors: Nicolo Matteo Luca Battisti, Marina Sehovic, Martine Extermann
Journal: Journal of Clinical Oncology (2015)

e20539 Background: Elderly patients in randomized clinical trials (RCTs)are a highly selected population not representative of an average clinical population. NCCN and ESMO guidelines for non-small cell lung cancer (NSCLC) are based on those RCTs, so their external validity is not well established. We assessed how well these RCT-based guidelines would match an elderly population at our institution. Methods: We retrieved RCTs addressing different questions from the guidelines. We matched the eligibility criteria in a population of NSCLC patients over 80 from our institutional database to check what proportion of them would have qualified or not for each trial. We ranked their validity with a cutoff of more than 60% for validity, 30-60% for partial validity and less than 30% for non-validity. Results: We collected data from 760 patients. In stage-adjusted groups, 41.57% would have qualified for the RCT addressing lobectomy or limited resection in T1N0 disease in both guidelines. 77.85% would have been enrolled in at least one of the 5 RCTs about mediastinal dissection from NCCN guidelines and 67.13% in the 2 RCTs from ESMO guidelines. 60.34% would have been eligible for the 2 RCTs about neoadjuvant chemoradiotherapy from NCCN guidelines and 31.03% for the RCT from ESMO guidelines. 97.44% would have qualified for the 15 RCTs about maintenance therapy from NCCN guidelines and 87.18% for the 5 RCTS from ESMO guidelines. Conclusions: In patients over 80 both guidelines are partially valid as for to the use of lobectomy versus limited resection in T1N0 disease. They are valid regarding mediastinal dissection and maintenance therapy, while NCCN guidelines are partially valid and ESMO guidelines have limited validity as for the use of neoadjuvant chemoradiotherapy before surgery.