tbuckley/cabot-search huggingface dataset:
Evaluating if an Advance Care Planning Intervention Promotes Do-Not-Resuscitate Orders by Facilitating Accurate Prognostic Awareness
Authors: Fur-Hsing Wen, Chen Hsiu Chen, Wen-Chi Chou, Jen-Shi Chen, Wen-Cheng Chang, Chia-Hsun Hsieh, Siew Tzuh Tang
Journal: Journal of the National Comprehensive Cancer Network (2020)

Issuing do-not-resuscitate (DNR) orders has seldom been an outcome in randomized clinical trials of advance care planning (ACP) interventions. The aim of this study was to examine whether an ACP intervention facilitating accurate prognostic awareness (PA) for patients with advanced cancer was associated with earlier use of DNR orders.Participants (n=460) were randomly assigned 1:1 to the experimental and control arms, with 392 deceased participants constituting the final sample of this secondary analysis study. Participants in the intervention and control arms had each received an intervention tailored to their readiness for ACP/prognostic information and symptom-management education, respectively. Effectiveness in promoting a DNR order by facilitating accurate PA was determined by intention-to-treat analysis using multivariate logistic regression with hierarchical linear modeling.At enrollment in the ACP intervention and before death, 9 (4.6%) and 8 (4.1%) participants and 168 (85.7%) and 164 (83.7%) participants in the experimental and control arms, respectively, had issued a DNR order, without significant between-arm differences. However, participants in the experimental arm with accurate PA were significantly more likely than participants in the control arm without accurate PA to have issued a DNR order before death (adjusted odds ratio, 2.264; 95% CI, 1.036-4.951; P=.041). Specifically, participants in the experimental arm who first reported accurate PA 31 to 90 days before death were significantly more likely than their counterparts in the control arm who reported accurate PA to have issued a DNR order in the next wave of assessment (adjusted odds ratio, 13.365; 95% CI, 1.989-89.786; P=.008). Both arms issued DNR orders close to death (median, 5-6 days before death).Our ACP intervention did not promote the overall presence of a DNR order. However, our intervention facilitated the issuance of NDR orders before death among patients with accurate PA, especially those who reported accurate PA 31 to 90 days before death, but it did not facilitate the issuance of DNR orders earlier than their counterparts in the control arm.ClinicalTrial.gov Identification: NCT01912846.
BIOM-07. EXPRESSION OF ANDROGEN RECEPTOR AND PROGRAMMED DEATH-LIGAND 1 IN BREAST-TO-BRAIN-METASTASES.
Authors: Maleeha Qazi, Katarzyna Jerzak, Sharon Nofech-Mozes
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Therapies targeting androgen receptors (AR) and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated intracranial activity. In this study, we analyzed the expression of AR and PD-L1 in breast cancer brain metastases (BrM) to identify patients who may benefit from anti-androgenic or anti-PD-1/PD-L1 therapies. METHODS Consecutive BrM resected in our institution (July 1999-June 2013) that were signed out as breast origin were identified and included from the Anatomic Pathology departmental database. A tissue microarray of BrMs was studied by immunohistochemistry for AR, PD-L1, ER, PR and HER2 (SP107, SP142, SP1, IE2, 4B5; Ventana Medical Systems). HER2 gene amplification was determined by INFORM HER2 DNA and Chromosome 17 (Ventana Medical Systems). Immunohistochemistry was used as a surrogate to determine intrinsic subtypes. RESULTS Among 61 breast cancer BrM with available tissue blocks, AR was expressed in 38 (62%) cases and PD-L1 was expressed in 9 (15%) cases. Among BrMs of luminal A subtype (ER+PR+/-HER2-Ki67&amp;lt; 16%; n=2), 50% expressed AR and none expressed PD-L1. Within the luminal B subtype (ER+/PR+/-), all 15 HER2+ BrM expressed AR (100%), while only 1 expressed PD-L1 (7%). Among HER2- luminal B subtype BrMs (n=16), 50% and 12.5% of cases expressed AR and PD-L1, respectively. In BrM of HER2+ subtype (ER-/PR-; n=14), 71% expressed AR and 14% expressed PD-L1. The frequency of AR+ (30%) and PD-L1+ (30%) cases was equivalent in triple negative BrM (ER-/PR-/HER2-; n=14). CONCLUSION Almost two-thirds of breast cancer BrM expressed AR, while only 15% expressed PD-L1. HER2+ luminal B and HER2+ subtypes were most likely to be AR+. Meanwhile, PD-L1 expression was predominant in the triple negative subgroup. Our data suggests that certain subtypes of breast cancer BrM are more likely to be AR+ or PD-L1+; intracranial efficacy of AR-antagonists and immunotherapy warrants investigation for breast cancer BrM, particularly in biomarker-positive subtypes.
Probiotics for treatment of nonalcoholic fatty liver disease: It is worth a try
Authors: Tian-Yi Ren, Xiao-Yan Li, Jian-Gao Fan
Journal: Clinical and Molecular Hepatology (2020)

See the Original "Lactobacillus attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis" on page 110.
Should her name begin with “Doctor”?
Authors: Julie K Silver
Journal: BMJ (2020)

What we call ourselves, and how others refer to us, matters. This is perhaps nowhere more important than in a professional setting, where the use of titles or first names has the potential to bring up gender and equity issues. A recent column in The BMJ by David Oliver on whether doctors should use their first names,1 started a lively debate in the rapid responses, with many responses coming from US women. Oliver wrote, “Personally, I set great store by being human and approachable and would never insist on using titles: ‘David’ is fine.” As a workforce gender equity researcher, I was invited to discuss this important topic.

Oliver begins, “I work in an 800 bed hospital employing over 4000 people, yet everyone knows the chief executive and the chief operating officer as ‘Steve’ and ‘Dom.’” Notably, these examples are men, so one might consider how the culture of using first names may be influenced by a cloak of privilege at the top. After all, women in the US and many other countries are often represented in top leadership positions at very low levels. For example, there are more men named John than there are women in many leadership positions.2 A deep dive into the promotion of women in medicine by Richter and colleagues, studying more than 500 000 graduates from 134 US …
Estrogen-induced circRNA, circPGR, functions as a ceRNA to promote estrogen receptor-positive breast cancer cell growth by regulating cell cycle-related genes
Authors: Lei Wang, Jia Yi, Ling-yun Lu, Yue-ying Zhang, Lan Wang, Guo-sheng Hu, Yi-chen Liu, Jian-cheng Ding, Hai-feng Shen, Fang-qing Zhao, Hai-hua Huang, Wen Liu
Journal: Theranostics (2020)

Estrogen and estrogen receptor (ER)-regulated gene transcriptional events have been well known to be involved in ER-positive breast carcinogenesis. Meanwhile, circular RNAs (circRNAs) are emerging as a new family of functional non-coding RNAs (ncRNAs) with implications in a variety of pathological processes, such as cancer. However, the estrogen-regulated circRNA program and the function of such program remain uncharacterized. Methods: CircRNA sequencing (circRNA-seq) was performed to identify circRNAs induced by estrogen, and cell proliferation, colony formation, wound healing, transwell and tumor xenograft experiments were applied to examine the function of estrogen-induced circRNA, circPGR. RNA sequencing (RNA-seq) and ceRNA network analysis wereperformed to identify circPGR's target genes and the microRNA (miRNA) bound to circPGR. Anti-sense oligonucleotide (ASO) was used to assess circPGR's effects on ER-positive breast cancer cell growth. Results: Genome-wide circRNA profiling by circRNA sequencing (circRNA-seq) revealed that a large number of circRNAs were induced by estrogen, and further functional screening for the several circRNAs originated from PGR revealed that one of them, which we named as circPGR, was required for ER-positive breast cancer cell growth and tumorigenesis. CircPGR was found to be localized in the cytosol of cells and functioned as a competing endogenous RNA (ceRNA) to sponge miR-301a-5p to regulate the expression of multiple cell cycle genes. The clinical relevance of circPGR was underscored by its high and specific expression in ER-positive breast cancer cell lines and clinical breast cancer tissue samples. Accordingly, anti-sense oligonucleotide (ASO) targeting circPGR was proven to be effective in suppressing ER-positive breast cancer cell growth. Conclusions: These findings reveled that, besides the well-known messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (lncRNA) and enhancer RNA (eRNA) programs, estrogen also induced a circRNA program, and exemplified by circPGR, these estrogen-induced circRNAs were required for ER-positive breast cancer cell growth, providing a new class of therapeutic targets for ER-positive breast cancer.
Intravenous Acetaminophen in Postoperative Patients—Reply
Authors: Alparslan Turan, Daniel I. Sessler
Journal: JAMA (2020)

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Intercellular Transmission of Hepatic ER Stress in Obesity Disrupts Systemic Metabolism
Authors: Amir Tirosh, Gurol Tuncman, Ediz S. Calay, Moran Rathaus, Idit Ron, Amit Tirosh, Abdullah Yalcin, Yankun G. Lee, Rinat Livne, Sophie Ron, Neri Minsky, Ana Paula Arruda, Gökhan S. Hotamisligil
Journal: Cell Metabolism (2020)
A traumatic elbow injury
Authors: Murtaza Kadhum, Pierre Sinclair, Daniel Rolton
Journal: BMJ (2020)

A 4 year old boy presented with pain in his right elbow after a fall from a bicycle onto his outstretched hand. His father had noticed him lying on his arm after the fall. The patient was guarding his right elbow in a flexed and adducted position.

On examination, this was a closed injury with no obvious clinical deformity, swelling, or skin changes to the elbow; distally, the radial pulse was present and the median (including anterior interosseus), radial, and ulnar nerves were intact. No other injuries were identified. Observations were normal. Lateral and anteroposterior plain radiographs were taken (fig1, fig 2).



Fig 1 
Anteroposterior plain radiograph of right elbow





Fig 2 
Lateral plain radiograph of right elbow



What is the diagnosis?

Supracondylar fracture of the …
Correction
Journal: Journal of the American Society of Nephrology (2020)

Farkash EA, Wilson AM, Jentzen JM: Ultrastructural evidence for direct renal infection with SARS-CoV-2. J Am Soc Nephrol 31: [1683–1687][1], 2020. There are two locations where the dimensions are listed incorrectly in µ m when they should be in nm. The first is in the abstract: “averaged 76
RARE-48. CHARACTERISTICS AND OUTCOME OF DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT): A SINGLE INSTITUTION EXPERIENCE
Authors: Emily Owens Pickle, Ana Aguilar-Bonilla, Amy Smith
Journal: Neuro-Oncology (2020)

Abstract Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare with an unknown etiology and unestablished incidence. Most frequently reported genetic alteration is KIAA1549-BRAF fusion. We present four DLGNT cases diagnosed between 2005–2018. Patient 1 is a female who presented with a 2-year history of back pain subsequently diagnosed with pilocytic astrocytoma. Re-imaging 3 months post-resection revealed a low grade glioneuronal tumor with BRAF duplication. Patient 2 is a female who presented with recurrent vomiting, dizziness, and hydrocephalus. The patient underwent biopsy which was consistent with oligodendrogliomatosis; no genetic analysis was done. Patient 3 is a male who presented with worsening headaches and intermittent vomiting. Approximately 5 months after resection, imaging showed leptomeningeal disease and further testing revealed KIAA1549-BRAF fusion and 1p deletion. Patient 4 is a male who presented with hydrocephalus. Imaging showed disseminated leptomeningeal enhancement without a dominant mass lesion; biopsy and clinical history confirmed the diagnosis. All four patients received chemotherapy, Patients 1 and 3 underwent radiation therapy, and Patient 3 received a MEK-inhibitor to which he had a great response. However, the patient was non-compliant and had PD which continued despite re-starting therapy. Patients 1, 2, and 3 have died of progressive disease; survival was Patient 1, 276 days, Patient 2, approximately 7 years and 8 months, and Patient 3, 2 years and 11 months. Patient 4 remains alive with disease 4.5 years from diagnosis. There is much to be learned about this rare, poorly understood disease but hope for improvement through therapeutic targeting of the MAPK pathway.
Use of Mouse Models to Evaluate Novel Therapeutic Approaches to Treatment of Arrhythmogenic Right Ventricular Cardiomyopathy: The Future Is Now⁎⁎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: Hugh Calkins
Journal: Journal of the American College of Cardiology (2011)
EXTH-02. TUMOR-HOMING INDUCED NEURAL STEM CELL THERAPY INHIBITS THE PROGRESSION OF BREAST CANCER BRAIN METASTASIS AND LEPTOMENINGEAL CARCINOMATOSIS
Authors: Wulin Jiang, Alain Valdivia, Alison Mercer-Smith, Carey Anders, Shawn Hingtgen
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Breast cancer brain metastasis, including leptomeningeal carcinomatosis (LC), remains one of the most lethal CNS diseases. New therapies are urgently needed to treat this highly aggressive disease. Here we used models of both breast cancer brain parenchymal metastasis and leptomeningeal metastasis to investigate the efficacy of engineered tumor-homing neural stem cells (NSCs) therapy. METHODS Personalized NSCs were created using Sox2 overexpression to transdifferentiate human fibroblasts into induced NSCs (iNSCs), followed by genetic engineering to enable iNSCs to secrete cytotoxic TRAIL (iNSC-TRAIL). For the parenchymal metastasis study, iNSC-TRAIL therapy was infused intracerebroventricularly (ICV) into Nude mice bearing established intracranial MDA-MB-231-Br human breast cancer cells expressing fluorescent and bioluminescent reporters. For LC studies, we established the disease model by inoculating Nude mice with MDA-MB-231-Br tumor cells via intracisternal infusion. iNSC-TRAIL therapy was evaluated by infusing therapy ICV either 1 week prior to or 3 days after tumor inoculation to mirror prophylactic or established tumor treatment, respectively. Tumor progression in the brain and spine was monitored by serial bioluminescence imaging (BLI), and survival was analyzed. RESULTS Serial BLI showed ICV-infused iNSC-TRAIL reduced parenchymal tumor volumes by 72% 3 weeks post-ICV infusion, and extended median survival from 37 to 52 days. Testing iNSC-TRAIL therapy against established LC tumors, serial BLI showed ICV iNSC-TRAIL therapy reduced established tumors 196-fold in the brain and 500-fold in the spine within 2 weeks post-infusion, while extending median survival from 25 to 47 days. In the prophylactic LC model, iNSC-TRAIL therapy markedly delayed tumor development with tumors in the brain remaining &amp;gt; 1000-fold smaller than control, and tumors in the spine below the limit of detection through 1 month post-treatment. The therapy also eliminated mortality through 50 days post-therapy. CONCLUSION These data suggest iNSC therapy could be a promising treatment option for breast cancer brain metastasis patients.
BIOM-56. THE INTEGRATION OF A LIQUID BIOPSY PROGRAM INTO THE CARE OF PEDIATRIC BRAIN TUMOR PATIENTS
Authors: Alexandra Miller, Luca Szalontay, Hamza Ahmad, Nancy Bouvier, Irene Rodriguez-Sanchez, Tejus Bale, Ryma Benayed, Maria Arcila, Maria Donzelli, Ira Dunkel, Stephen Gilheeney, Yasmin Khakoo, Kim Kramer, Sameer Farouk Sait, Mark Souweidane, Ingo Mellinghoff, Matthias Karajannis
Journal: Neuro-Oncology (2020)

Abstract Pediatric CNS tumors remain the leading cause of cancer-related death in children and adolescents. Safe sampling of tumor tissue for diagnostic purposes may be difficult if not impossible. Detection of minimal residual or recurrent disease prior to definitive clinical or radiographic progression may allow earlier initiation of novel therapies and ultimately improve overall survival. Given the rarity of serial sampling of tumor tissue, our understanding of molecular evolution in response to therapy remains limited. Recent technological advances have led to the development of “liquid biopsy” assays, which detect cell-free DNA (cfDNA) in blood, cerebrospinal fluid (CSF) or other bodily fluids. Here, we report our initial clinical experience with the recently established MSK Kids pediatric neuro-oncology liquid-biopsy program at Memorial Sloan Kettering Cancer Center (MSKCC) using MSK-IMPACT, which is clinically validated by the New York State Department of Health for CSF cell-free DNA (cfDNA)vprofiling. All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. Samples from 29 unique patients were sequenced. Histopathology included high-grade glioma (5); low-grade glioma (2); medulloblastoma (8); pineoblastoma (3); retinoblastoma (4); other (7). CSF cfDNA could be detected in 18/42 samples (43%) and 12/29 patients (34%). CSF cfDNA was more commonly detected in higher-grade, disseminated tumors such as high-grade glioma (60%), medulloblastoma (38%), and pineoblastoma (100%). Low-grade lesions without leptomeningeal involvement did not result in detectable CSF cfDNA shedding (86% were negative). In a subset of patients, MSK-IMPACT identified previously unrecognized molecular actionable targets (e.g. BRAF-KIAA1549 fusion); or the detection of “minimal residual disease” prior to the detection of tumor recurrence by conventional diagnostics, impacting clinical care decisions. Future directions include integration of CSF cfDNA into prospective clinical trials as a correlative biomarker.
Blueprint for cancer research: Critical gaps and opportunities
Authors: Lynne W. Elmore, Susanna F. Greer, Elvan C. Daniels, Charles C. Saxe, Michael H. Melner, Ginger M. Krawiec, William G. Cance, William C. Phelps
Journal: CA A Cancer Journal for Clinicians (2020)

Abstract We are experiencing a revolution in cancer. Advances in screening, targeted and immune therapies, big data, computational methodologies, and significant new knowledge of cancer biology are transforming the ways in which we prevent, detect, diagnose, treat, and survive cancer. These advances are enabling durable progress in the goal to achieve personalized cancer care. Despite these gains, more work is needed to develop better tools and strategies to limit cancer as a major health concern. One persistent gap is the inconsistent coordination among researchers and caregivers to implement evidence‐based programs that rely on a fuller understanding of the molecular, cellular, and systems biology mechanisms underpinning different types of cancer. Here, the authors integrate conversations with over 90 leading cancer experts to highlight current challenges, encourage a robust and diverse national research portfolio, and capture timely opportunities to advance evidence‐based approaches for all patients with cancer and for all communities.
Retina as a window to cerebral dysfunction following studies with circRNA signature during neurodegeneration
Authors: Qin Jiang, Dong-Yuan Su, Zhen-Zhen Wang, Chang Liu, Ya-Nan Sun, Hong Cheng, Xiu-Miao Li, Biao Yan
Journal: Theranostics (2020)

Ischemia-induced cerebral injury is a major cause of dementia or death worldwide. The pre-diagnosis is still challenging due to the retarded symptoms. The retina is regarded as the extension of cerebral tissue. Circular RNAs have emerged as the crucial regulators in gene regulatory network and disease progression. However, it is still unknown whether circRNAs can be used as the common regulators and diagnostic markers for cerebral neurodegeneration and retinal neurodegeneration.
NCOG-44. NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY (NANO) SCALE IN A PHASE II STUDY OF PEMBROLIZUMAB OR PEMBROLIZUMAB PLUS BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Lakshmi Nayak, Annette Molinaro, Katherine Peters, Jennifer Clarke, Justin Jordan, John de Groot, Phioanh Nghiemphu, Thomas Kaley, Howard Colman, Christine McCluskey, Sarah Gaffey, Timothy Smith, David Cote, Mariano Severgnini, Jennifer Yearley, Qing Zhao, Wendy Blumenschein, Gabriel Duda, Alona Muzikansky, Rakesh Jain, Patrick Wen, David Reardon
Journal: Neuro-Oncology (2020)

Abstract PURPOSE The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in brain tumor patients to complement radiographic assessment in defining overall outcome. A multicenter, phase 2 study of pembrolizumab with or without bevacizumab in patients with recurrent glioblastoma incorporated the NANO scale as an exploratory endpoint. METHODS Neurologic examination was evaluated at baseline and MRI assessments using the NANO scale until patients came off study. Statistical descriptive data analysis was performed using R (version 3.4.3). Correlation analysis utilized Fisher’s exact test. RESULTS NANO compliance rate was 94% in 80 patients accrued on the study. Of the 80 patients, 7 were missing NANO at baseline visit and were excluded from analysis for NANO response criteria. Fifteen patients did not have end of treatment NANO evaluation. Of 73 patients, 35 (48%) had a normal neurologic examination at baseline by NANO. Strength and language accounted for the majority of changes in neurologic function over the course of study treatment. Eighteen patients (25%) had neurologic progression by NANO, of whom 2 did not have concurrent radiographic progression. Three patients (pembrolizumab plus bevacizumab cohort) had a neurologic response associated with stable disease on MRI. NANO assessment prior to initiation of cycle 3 correlated with RANO response (p=0.011), change in KPS (p=0.002) and dexamethasone requirement (p=0.007) while those with NANO progression at this assessment had worse overall survival (291 vs 324 days), but this trend did not achieve statistical significance (p=0.2). CONCLUSIONS Evaluation of neurologic function by NANO scale was feasible in a multicenter prospective study in patients with GBM with a high compliance rate. The NANO scale objectively tracked stable neurologic function in most patients throughout the trial period and was associated with a trend for survival.