tbuckley/cabot-search huggingface dataset:
QIM19-129: Utilization of Electronic Medical Record to Improve Outcomes in the Treatment of Febrile Neutropenia
Authors: Anna M. Gibson, Claire Sutherby
Journal: Journal of the National Comprehensive Cancer Network (2019)

Introduction: Chemotherapy-induced febrile neutropenia is a medical emergency. Delays in time to appropriate broad spectrum antibiotic therapy significantly increase morbidity and mortality. The purpose of this project is to improve outcomes in febrile neutropenia patients within our institutions by hard wiring compliance to NCCN Guidelines and IDSA guidelines via our electronic medical record (EMR). Methods: During initial chemo teaching, patients were instructed to present for emergency care immediately on noticing a fever. Patients were given a pocket card stating that the patient had recently received chemotherapy, indicating the patient’s neutropenia risk, and listing directions to a newly created febrile neutropenia page on the health system’s website. ED staff was educated that chemotherapy patients presenting with fever should be triaged to a high acuity level, which resulted in the patient being roomed immediately and seen promptly. The EMR dashboard for ED staff was modified to include a section for febrile neutropenia, which included links to appropriate antibiotics and directions to hang immediately after blood cultures were drawn. The admission order set was also modified to include protective isolation and guideline-based antibiotic choices. 2 months following implementation, patients were pulled based on ICD10 codes for fever/infection and chemotherapy/cancer. 23 patients were identified who met the study criteria (10 patients pre-implementation, 13 patients post-implementation). Pediatric patients and patients admitted directly to the floor were excluded from analysis. Results: While numbers were small, there were 15 patients admitted during the study period. Eight patients met study criteria pre-initiative and seven post-initiative. Pre-initiative: 6 of 8 patients were roomed immediately; 6 of 8 patients received appropriate empiric antibiotics; 1 of 8 patients received first dose within 1 hour of presentation to ED. Post-initiative: 7 of 7 patients were roomed immediately; 6 of 7 patients received appropriate empiric antibiotics; 4 of 7 patients received first dose within 1 hour of presentation to ED. Conclusions: Despite small numbers and incomplete compliance with guidelines, we were able to identify a 2.8 day decrease in average length of stay (LOS) and a 1.3 day decrease in ICU LOS. Sample size was not large enough to determine statistical significance.
Disruption of tumour-associated macrophage trafficking by the osteopontin-induced colony-stimulating factor-1 signalling sensitises hepatocellular carcinoma to anti-PD-L1 blockade
Authors: Ying Zhu, Jing Yang, Da Xu, Xiao-Mei Gao, Ze Zhang, Jennifer L Hsu, Chia-Wei Li, Seung-Oe Lim, Yuan-Yuan Sheng, Yu Zhang, Jian-Hua Li, Qin Luo, Yan Zheng, Yue Zhao, Lu Lu, Hu-Liang Jia, Mien-Chie Hung, Qiong-Zhu Dong, Lun-Xiu Qin
Journal: Gut (2019)

In the tumour microenvironment, critical drivers of immune escape include the oncogenic activity of the tumour cell-intrinsic osteopontin (OPN), the expression of programmed death ligand 1 (PD-L1) and the expansion of tumour-associated macrophages (TAMs). We investigated the feasibility of targeting these pathways as a therapeutic option in hepatocellular carcinoma (HCC) mouse models.We analysed the number of tumour-infiltrating immune cells and the inflammatory immune profiles in chemically induced liver tumour isolated from wild-type and OPNknockout (KO) mice. In vitro cell cocultures were further conducted to investigate the crosstalk between TAMs and HCC cells mediated by OPN, colony stimulating factor-1 (CSF1) and CSF1 receptor (CSF1R). The in vivo efficacy of anti-PD-L1 and CSF1/CSF1R inhibition was evaluated in OPN overexpressing subcutaneous or orthotopic mouse model of HCC.The numbers of TAMs, as well as the expression levels of M2 macrophage markers and PD-L1 were significantly decreased, but the levels of cytokines produced by T-helper 1 (Th1) cells were upregulated in tumour tissues from OPN KO mice compared with that from the controls. In addition, we observed a positive association between the OPN and PD-L1 expression, and OPN expression and TAM infiltration in tumour tissues from patients with HCC. We further demonstrated that OPN facilitates chemotactic migration, and alternative activation of macrophages, and promotes the PD-L1 expression in HCC via activation of the CSF1-CSF1R pathway in macrophages. Combining anti-PD-L1 and CSF1R inhibition elicited potent antitumour activity and prolonged survival of OPNhigh tumour-bearing mice. Histological, flow cytometric and ELISA revealed increased CD8+ T cell infiltration, reduced TAMs and enhanced Th1/Th2 cytokine balance in multiple mouse models of HCC.OPN/CSF1/CSF1R axis plays a critical role in the immunosuppressive nature of the HCC microenvironment. Blocking CSF1/CSF1R prevents TAM trafficking and thereby enhances the efficacy of immune checkpoint inhibitors for the treatment of HCC.
Abstract 19932: Secular Trends in Complications of Atrial Fibrillation 2004-2012: The Treat-AF Study
Authors: Daniel W Kaiser, Alexander C Perino, Jun Fan, Susan Schmitt, Mintu P Turakhia
Journal: Circulation (2015)

Background: Limited data indicates that complications of atrial fibrillation (AF) may be declining. We evaluated secular trends in AF outcomes over 8 years using complete data from the largest integrated health care system in the United States. Methods: Using data from the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF between from 2004 to 2012. Using VA and linked Medicare data, we determined the incidence rates for ischemic stroke, intracranial hemorrhage, extracranial hemorrhage, hospitalization for heart failure, and death from inpatient claims and medical record data using validated algorithms. Results: In 184,161 patients with newly diagnosed AF (age 70.4±10.7; CHADS-VASC 2.6±1.7) the incidence rates, expressed as events per 1000 person-years, gradually decreased from 2004 to 2014 for ischemic stroke (12.1 to 8.0), intracranial hemorrhage (4.2 to 2.0), and death (86.3 to 63.7) (p &lt; 0.05 for all, Table 1). Heart failure incidence rates slightly increased (44.3 to 50.6). Extracranial hemorrhage events were relatively stable until 2010, when the events gradually decreased from 19.6 to 16.8 events per 1000 person-years. Conclusions: Among patients with newly-diagnosed AF from 2004-2012, the incidence rates of stroke (both hemorrhagic and ischemic), hemorrhage, and death have declined while heart failure admission rates have slightly increased. Causes and mediators require exploration but major sequelae following AF have dramatically changed.
BPI19-011: Assessment and Management of Older Patients With Metastatic Breast Cancer (MBC) Among Community Oncologists in the United States
Authors: Efrat Dotan, Elizabeth Handorf, Caitlin R. Meeker, Bianca Lewis, Kelly Filchner, Jennifer S. Winn, Lori J. Goldstein
Journal: Journal of the National Comprehensive Cancer Network (2019)

Introduction: Geriatric assessment (GA) is recommended for evaluating an older cancer patient’s fitness for treatment; however, it is underutilized in the community. We sought to define the gaps that exist in community oncology practices in the assessment and management of older MBC patients through implementation and training on the use of GA for the care of older MBC patients. Methods: The first phase evaluated community oncology providers using questionnaires regarding their assessment and management of older MBC patients. The second phase included training through implementation of a patient self-administered GA among patients ≥65-years-old with MBC. The providers were blinded to the results of the GA and provided their assessment. Comparison of the 2 evaluations was conducted. The GA was ultimately shared with the providers, who were questioned about the effect of the results on care recommendations. Results: 43 providers from 10 practices were enrolled. Phase I revealed the majority (77%) of providers recognized the utility of GA, yet only 42% routinely conducted a GA pretreatment. Most providers (77%) reported evaluating various GA domains through patient interview rather than validated assessments. Validated scales were used in low rates to evaluate cognition (23%), psychosocial status (12%), and toxicity risk (9%). The limited use of validated assessment tools was not influenced by the provider’s demographics or their views of GA utility. Eighty patients took part in the training phase of the study to date, with average age 74 (range, 65–90) and 84% Caucasian. The majority of patients had subtype ER/PR+, HER2- (75%) and 46% were on first-line therapy. 277 recommended interventions were identified: 174 immediate interventions and 103 suggested interventions. Following review of these results, providers reported being surprised in 40% of the cases, mainly with lower than expected cognitive or social support scores. The providers reported plans for change in management in 44% of the patients as a result of the GA findings. Conclusion: Despite acknowledgement of the value associated with pretreatment GA, it is rarely used in the community. Furthermore, interview rather than validated assessment tools are used to identify age-related concerns. In our preliminary results, the GA identified a large number of deficient areas that had not been identified through the provider’s assessment, and resulted in management change. Additional updated results will be presented at the conference.
Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours
Authors: Han Yao, Jiang Lan, Chushu Li, Hubing Shi, Jean-Philippe Brosseau, Huanbin Wang, Haojie Lu, Caiyun Fang, Yao Zhang, Lunxi Liang, Xiaolin Zhou, Chaojun Wang, Yu Xue, Yun Cui, Jie Xu
Journal: Nature Biomedical Engineering (2019)
Racial Segregation and Inequality of Care in Neonatal Intensive Care Units Is Unacceptable
Authors: Elizabeth A. Howell, Paul L. Hebert, Jennifer Zeitlin
Journal: JAMA Pediatrics (2019)

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A Novel Peptide Interfering with proBDNF-Sortilin Interaction Alleviates Chronic Inflammatory Pain
Authors: Idy H.T. Ho, Xiaodong Liu, Yidan Zou, Taian Liu, Wei Hu, Hung Chan, Yuanyuan Tian, Yuchen Zhang, Qing Li, Shanglong Kou, Chee Sam Chan, Tony Gin, Christopher H.K. Cheng, Sunny H. Wong, Jun Yu, Lin Zhang, William K.K. Wu, Matthew T.V. Chan
Journal: Theranostics (2019)

Rationale: Brain-derived neurotrophic factor (BDNF) is a key mediator in the development of chronic pain.Sortilin is known to interact with proBDNF and regulate its activity-dependent secretion in cortical neurons.In a rat model of inflammatory pain with intraplantar injection of complete Freund's adjuvant (CFA), we examined the functional role of proBDNF-sortilin interaction in dorsal root ganglia (DRG).Methods: Expression and co-localization of BDNF and sortilin were determined by immunofluorescence.ProBDNF-sortilin interaction interface was mapped using co-immunoprecipitation and bimolecular fluorescence complementation assay.The analgesic effect of intrathecal injection of a synthetic peptide interfering with proBDNF-sortilin interaction was measured in the CFA model.Results: BDNF and sortilin were co-localized and their expression was significantly increased in ipsilateral L4/5 DRG upon hind paw CFA injection.In vivo adeno-associated virus-mediated knockdown of sortilin-1 in L5 DRG alleviated pain-like responses.Mapping by serial deletions in the BDNF prodomain indicated that amino acid residues 71-100 supported the proBDNF-sortilin interaction.A synthetic peptide identical to amino acid residues 89-98 of proBDNF, as compared with scrambled peptide, was found to interfere with proBDNF-sortilin interaction, inhibit activity-dependent release of BDNF in vitro and reduce CFA-induced mechanical allodynia and heat hyperalgesia in vivo.The synthetic peptide also interfered with capsaicin-induced phosphorylation of extracellular signal-regulated kinases in ipsilateral spinal cord of CFA-injected rats.Conclusions: Sortilin-mediated secretion of BDNF from DRG neurons contributes to CFA-induced inflammatory pain.Interfering with proBDNF-sortilin interaction reduced activity-dependent release of BDNF and might serve as a therapeutic approach for chronic inflammatory pain.
Risk for developing brain metastases from colorectal cancer in long-term survivors with lung metastases and KRAS mutations.
Authors: Federica Zoratto, Fotios Loupakis, Chiara Cremolini, Lisa Salvatore, Marta Schirripa, Carlotta Antoniotti, Federica Marmorino, Giuseppe Campenni, Francesca Bergamo, Vittorina Zagonel, Sara Lonardi, Silverio Tomao, Enrico Cortesi, Giacomo Allegrini, Sara Lucchesi, Manfredi Morvillo, Roberta Savi, Lorenzo Marcucci, Gabriele Minuti, Alfredo Falcone
Journal: Journal of Clinical Oncology (2013)

e14574 Background: Brain metastases (BM) occur in 1-4% of metastatic colorectal cancer (mCRC) patients (pts). Retrospective series evidence that pts with a long survival from the diagnosis of mCRC are more frequently affected. Moreover, BM seem to be associated with lung metastases and KRAS activating mutations. The identification of clinical and molecular features correlated with BM may allow to define a subgroup more likely to develop BM, thus to benefit from neuroimaging follow up and early treatment. Methods: We prospectively tested the hypothesis that a higher incidence of BM occurs in a population of mCRC pts with a survival time from the diagnosis of mCRC ≥10 months, lung metastases and KRAS exons 2 and 3 mutations. Given a reported incidence of BM in unselected mCRC of around 3% (H0) and expecting an incidence in an “at risk” population selected on the basis of the 3 above reported features of 10% (H1), setting α and β errors to 0.05 and 0.10 respectively, we adopted the Fleming single-stage design for calculating the sample size of our analysis. The null hypothesis would have been rejected if at least 7 out of 104 “at risk” pts had developed BM. Results: 623 pts, enrolled in clinical trials treated with first-line chemotherapy and bevacizumab, were included in the overall study population in order to identify 105 (16.9%) pts who simultaneously had a survival time from the diagnosis of mCRC ≥10 months, lung metastases and KRAS exons 2 and 3 mutations. 26 (4.2%) out of 623 pts developed BM. 14 out 518 (2.7%) not “at risk” pts presented BM, while 12 out of 105 (11.4%) “at risk” pts did. The incidence of BM in the two groups differed significantly (Fisher’s exact test, p=0.0004). The null hypothesis was rejected according to the original design. Conclusions: This analysis confirms the hypothesis that the concomitant presence of the 3 analyzed risk factors increases the probability of developing BM in mCRC patients. Based on these data, the opportunity to consider a neuroimaging exam, such as brain CT scan or MRI, in this specific population might be taken into account in order to provide an early diagnosis of BM and therefore the most appropriate therapy in an asymptomatic phase.
QIM19-116: Barriers and Trends in Cancer Patients’ referrals to Pain Management in Qatar: A Randomized Cohort Prospective Study
Authors: Rehab Abdelwahab, Anas Hamad, Shereen El Azzaz, Randa Al Okka, Mohd A. Wahid, Khalil Ullah Shibli, Ahmed El Geziry, Fathi Saleh, Kakil Rasul, Wael Saleem
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Studies showed that 40%–50% of patients with cancer pain receive insufficient analgesia due to different factors (Beyeler et al, Support Care Cancer 2008; Salminen et al, Support Cancer Care 2008), beside the challenges to accurately assess pain, which might affect drug selection and pain control (Stewart, Ulster Med J 2014). In NCCCR, the treating primary physicians (PP) may prescribe analgesics to their patients or refer them to the Pain Management Team (PMT), based on evaluation or as requested by patients. This study will address the clinical concerns of PP, which may lead to refer the patients to PMT, moreover the clinical judgement of PMT on the referred cases whether they need to be refereed or not. Objectives : To determine the efficiency of the referral pathway to the pain clinic by PMT. Methods: PMT is going to assess the referred patient to their clinics according to pain assessment methods. Patients will be evaluated whether they have been appropriately referred or not, any unnecessary referral will be documented based on the following; • If the patient was referred by hematologist or oncologist • If the patient required specialized treatment • If the patient required urgent treatment/prescription or advanced pain management techniques • If the patient required further consultation by pain management • If the patient could be managed by PP Results: 195 patients were newly referred to the pain clinic during the period from March 8, 2018 to August 31, 2018. 12% (23/195) were deemed as unnecessary referrals based on PMT assessment; 43% (10/23) of them were hematology patients, while 57% (13/23) were oncology. The majority was for breast cancer and sickle cell disease patients with 35% for each. According to the PMT assessment, 61% (14/23) patients (95% CI, 40.79%–77.84%) considered unnecessary referrals due to improper basic pain assessment and management by PP, while 30% (7/23) patients (95%CI, 15.60%–50.87%) asked for refill medications. Conclusion: There is 12% unnecessary referrals to PMT, which need further improvement in the referral pathway, via the development of a definite referral criteria to PMT. PP should be encouraged to provide basic pain treatment and to consider multidisciplinary management with appropriate coordination for better improvements in patients’ quality of life.
Adoptive Transfers of Plasmacytoid Dendritic Cells after Hematopoietic Stem Cell Transplantation Decrease the Risk Acute Lymphoblastic Leukemia Relapse without Increasing the Risk of Graft-Versus-Host-Disease
Authors: Sabine Herblot, Valérie Paquin, Paulo Cordeiro, Michel Duval
Journal: Blood (2018)
Response to Comment on Lacy et al. Long-term Glycemic Control and Dementia Risk in Type 1 Diabetes. Diabetes Care 2018;41:2339–2345
Authors: Mary E. Lacy, Paola Gilsanz, Andrew J. Karter, Charles P. Quesenberry, Mark J. Pletcher, Rachel A. Whitmer
Journal: Diabetes Care (2019)

We thank Medrano-De-Avila et al. (1) for their interest in our study (2) on long-term glycemic control and dementia risk among older adults with type 1 diabetes.

In our study, the principal finding was that individuals with majority exposure to HbA1c 8–8.9% or HbA1c ≥9% had higher rates of dementia. A secondary finding was the suggestion that majority exposure to HbA1c <6% was potentially associated with a slightly (albeit statistically nonsignificant) increased risk of dementia. As Medrano-De-Avila et al. point out, prior studies have identified an association between hypoglycemia and dementia in …
Effectiveness of Self-guided App-Based Virtual Reality Cognitive Behavior Therapy for Acrophobia: A Randomized Clinical Trial
Authors: Tara Donker, Ilja Cornelisz, Chris van Klaveren, Annemieke van Straten, Per Carlbring, Pim Cuijpers, Jean-Louis van Gelder
Journal: JAMA Psychiatry (2019)

Globally, access to evidence-based psychological treatment is limited. Innovative self-help methods using smartphone applications and low-cost virtual reality have the potential to significantly improve the accessibility and scalability of psychological treatments.To examine the effectiveness of ZeroPhobia, a fully self-guided app-based virtual reality cognitive behavior therapy (VR CBT) using low-cost (cardboard) virtual reality goggles compared with a wait-list control group and to determine its user friendliness.In a single-blind randomized clinical trial, participants were enrolled between March 24 and September 28, 2017, and randomly assigned (1:1) by an independent researcher to either VR CBT app or a wait-list control group. A total of 193 individuals aged 18 to 65 years from the Dutch general population with acrophobia symptoms and access to an Android smartphone participated. The 6 animated modules of the VR-CBT app and gamified virtual reality environments were delivered over a 3-week period in participants' natural environment. Assessments were completed at baseline, immediately after treatment, and at 3-month follow-up. Analysis began April 6, 2018, and was intention to treat.Self-guided app-based VR CBT.The primary outcome measure was the Acrophobia Questionnaire. The hypothesis was formulated prior to data collection.In total, 193 participants (129 women [66.84%]; mean [SD] age, 41.33 [13.64] years) were randomly assigned to intervention (n = 96) or a wait-list control group (n = 97). An intent-to-treat analysis showed a significant reduction of acrophobia symptoms at posttest at 3 months for the VR-CBT app compared with the controls (b = -26.73 [95% CI, -32.12 to -21.34]; P < .001; d = 1.14 [95% CI, 0.84 to 1.44]). The number needed to treat was 1.7. Sensitivity and robustness analysis confirmed these findings. Pretreatment attrition was 22 of 96 (23%) because of smartphone incompatibility. Of the 74 participants who started using the VR-CBT app, 57 (77%) completed the intervention fully.A low-cost fully self-guided app-based virtual reality cognitive behavioral therapy with rudimentary virtual reality goggles can produce large acrophobia symptom reductions. To our knowledge, this study is the first to show that virtual reality acrophobia treatment can be done at home without the intervention of a therapist.Trialregister.nl identifier: NTR6442.
Vascular Inflammation in Subclinical Atherosclerosis Detected by Hybrid PET/MRI
Authors: Leticia Fernández-Friera, Valentín Fuster, Beatriz López-Melgar, Belén Oliva, Javier Sánchez-González, Angel Macías, Braulio Pérez-Asenjo, Daniel Zamudio, Juan C. Alonso-Farto, Samuel España, José Mendiguren, Héctor Bueno, Jose M. García-Ruiz, Borja Ibañez, Antonio Fernández-Ortiz, Javier Sanz
Journal: Journal of the American College of Cardiology (2019)