tbuckley/cabot-search huggingface dataset:
Association of a Bundled Hospital-at-Home and 30-Day Postacute Transitional Care Program With Clinical Outcomes and Patient Experiences
Authors: Alex D. Federman, Tacara Soones, Linda V. DeCherrie, Bruce Leff, Albert L. Siu
Journal: JAMA Internal Medicine (2018)

Hospital-at-home (HaH) care provides acute hospital-level care in a patient's home as a substitute for traditional inpatient care. In September 2017, the Physician-Focused Payment Model Technical Advisory Committee recommended implementation of an alternative payment model for a new model of HaH that bundles the acute episode with 30 days of postacute transitional care.To report outcomes of this new payment model for HaH care.Case-control study of HaH care patients with a concurrent control group of hospital inpatients recruited from emergency departments (EDs) and residences in New York City from November 18, 2014, to August 31, 2017. HaH patients were 18 years or older with fee-for-service Medicare and acute medical illness requiring inpatient-level care. Control patients met HaH eligibility but refused participation or were seen in the ED when a HaH admission could not be initiated.HaH care or inpatient care.Primary outcomes were acute period length of stay (LOS), all-cause 30-day hospital readmissions and ED visits, admissions to skilled nursing facilities (SNFs), referral to a certified home health care agency, and patient experiences with care. Analyses accounted for nonrandom selection using inverse probability weighting.Among the 507 patients enrolled (mean [SD] age, 74.6 [15.7] years; 68.6% women), data were available on all patients 30 days postdischarge. HaH patients (n = 295) were older than controls (n = 212) and more likely to have a preacute functional impairment. HaH patients had shorter LOS (3.2 days vs 5.5 days; difference, -2.3 days; 95% CI, -1.8 to -2.7 days; weighted P < .001); lower rates of readmissions (8.6% [25] vs 15.6% [32]; difference, -7.0%; 95% CI, -12.9% to -1.1%; weighted P < .001), ED revisits (5.8% [17] vs 11.7% [24]; difference, -5.9%; 95% CI, -11.0% to -0.7%; weighted P < .001), and SNF admissions (1.7% [5] vs 10.4% [22]; difference, -8.7%; 95% CI, -13.0% to -4.3%; weighted P < .001); and were also more likely to rate their hospital care highly (68.8% [119] vs 45.3% [67]; difference, 23.5%; 95% CI, 12.9% to 34.1%; weighted P < .001). There were no differences in referrals to certified home health agencies.HaH care bundled with a 30-day postacute transitional care episode was associated with better patient outcomes and ratings of care compared with inpatient hospitalization. This model warrants consideration for addition to Medicare's current portfolio of shared savings programs.
The effect of light sensitizer localization on the stability of indocyanine green liposomes
Authors: Tatu Lajunen, Riikka Nurmi, Danny Wilbie, Teemu Ruoslahti, Niklas G. Johansson, Ossi Korhonen, Tomasz Rog, Alex Bunker, Marika Ruponen, Arto Urtti
Journal: Journal of Controlled Release (2018)

Light triggered drug delivery systems offer attractive possibilities for sophisticated therapy, providing both temporal and spatial control of drug release. We have developed light triggered liposomes with clinically approved indocyanine green (ICG) as the light sensitizing compound. Amphiphilic ICG can be localized in different compartments of the liposomes, but the effect of its presence, on both triggered release and long term stability, has not been studied. In this work, we report that ICG localization has a significant effect on the properties of the liposomes. Polyethylene glycol (PEG) coating of the liposomes leads to binding and stabilization of the ICG molecules on the surface of the lipid bilayer. This formulation showed both good storage stability in buffer solution (at +4–37 °C) and adequate stability in serum and vitreous (at +37 °C). The combination of ICG within the lipid bilayer and PEG coating lead to poor stability at elevated temperatures of +22 °C and + 37 °C. The mechanisms of the increased instability due to ICG insertion in the lipid bilayer was elucidated with molecular dynamics simulations. Significant PEG insertion into the bilayer was induced in the presence of ICG in the lipid bilayer. Finally, feasibility of freeze-drying as a long term storage method for the ICG liposomes was demonstrated. Overall, this is the first detailed study on the interactions of lipid bilayer, light sensitizer (ICG) and PEG coating on the liposome stability. The localization of the light triggering agent significantly alters the structure of the liposomes and it is important to consider these aspects in triggered drug delivery system design.
Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells
Authors: Mara Vinci, Anna Burford, Valeria Molinari, Ketty Kessler, Sergey Popov, Matthew Clarke, Kathryn R. Taylor, Helen N. Pemberton, Christopher J. Lord, Alice Gutteridge, Tim Forshew, Diana Carvalho, Lynley V. Marshall, Elizabeth Y. Qin, Wendy J. Ingram, Andrew S. Moore, Ho-Keung Ng, Saoussen Trabelsi, Dorra H’mida-Ben Brahim, Natacha Entz-Werle, Stergios Zacharoulis, Sucheta Vaidya, Henry C. Mandeville, Leslie R. Bridges, Andrew J. Martin, Safa Al-Sarraj, Christopher Chandler, Mariona Sunol, Jaume Mora, Carmen de Torres, Ofelia Cruz, Angel M. Carcaboso, Michelle Monje, Alan Mackay, Chris Jones
Journal: Nature Medicine (2018)
Abstract 18207: A Prospective, Single Arm Feasibility Study to Evaluate the Safety and Performance of a Novel Embolic Deflection Device in Patients Undergoing Transcatheter Aortic Valve Replacement: Results From the Deflect I Study
Authors: Alexandra Lansky, Andreas Baumbach, Stephanie M Meller, Adam Brickman, Pauliina Margolis, Jan Kovac, David Hildick- Smith, Cody Pietras, Peter D Heier, Szilard Voros, Michael Mullen
Journal: Circulation (2013)

Background: Stroke associated with transcatheter aortic valve replacement (TAVR) is primarily due to intra-procedural mechanical embolization of calcific atherosclerotic plaque. Filter-based embolic protection devices may address this devastating complication. Objectives: : The results of the novel TriGard TM embolic deflection device used in conjunction with (TAVR) in 20 consecutive patients in the DEFLECT I clinical trial. Methods: DEFLECT I is a prospective, multi-center, single arm study designed to demonstrate the safety and performance of the TriGard TM Embolic Deflection Device (EDD) (Keystone Heart, Caesarea Business Park, Israel), among patients undergoing TAVR. The EDD is designed to be positioned across all major cerebral arteries in the aortic arch. Primary endpoints were device performance and in-hospital device-related safety. A powered secondary endpoint was the number and volume of new diffusion-weighted magnetic resonance imaging (DW MRI) brain lesions from pre-procedure to 4±2 days post-procedure compared to historic controls. Results: : 20 consecutive patients undergoing TAVR were enrolled at 5 sites. All devices were positioned and retrieved successfully. The device performed as intended with complete vessel coverage until completion of the valve implant in 80% of cases. There were no in-hospital EDD-related adverse events. In-hospital procedure-related MACCE was 10% due to major disabling strokes in 2/20 patients occuring the day after the procedure. Compared with historical controls, the number of new ischemic brain lesions detected on DW MRI (70% vs. 76%) were similar; however, patients undergoing TAVR with the EDD demonstrated 94% reductions in the maximum lesion volume (p&lt;0.01) and maximum total lesion volume (p&lt;0.01) and a 65% reduction in mean lesion volume (p&lt;0.01) compared with historical controls. Conclusions: The DEFLECT I study demonstrated safety and feasibility of the TriGard TM device in patients undergoing TAVR. The TriGard TM device significantly reduced the total and maximum volume of cerebral ischemic brain lesions compared to historic controls.This study established proof of concept of the TriGard TM device and justifies further evaluation in a planned randomized clinical trial.
Peroral cholangioscopy of nivolumab-related (induced) ulcerative cholangitis in a patient with non-small cell lung cancer
Authors: Naosuke Kuraoka, Kazuo Hara, Shuji Terai, Yasushi Yatabe, Yoshitsugu Horio
Journal: Endoscopy (2018)

Approximately 10 % – 15 % of patients treated with nivolumab may develop grade 3/4 immuno-related adverse events (irAEs) [1] [2] [3]. Rash and diarrhea are the common irAEs, whereas there have been few reports of nivolumab-related cholangitis and its clinical features [4].
Abstract 19248: Exosomal miR-142 Derived From Diabetic Bone Marrow Endothelial Progenitor Cells Impairs Cardiac Reparative Abilities Post Myocardial Infarction
Authors: Venkata N Garikipati, Mohsin Khan, Suresh K Verma, Zhongjian Cheng, Yujia Yue, Emily Nickoloff, Cindy Benedict, Erhe Gao, David Goukassian, Raj Kishore
Journal: Circulation (2016)

Introduction:  Diabetes is associated with a higher incidence of myocardial infarction (MI). Bone marrow-derived endothelial progenitor cell (EPCs) therapy has been shown to attenuate left ventricular (LV) dysfunction after diabetic MI. Recently the therapeutic performance of stem cells is reported to be largely mediated via exosomes (Exo). However, the autologous transplantation of EPCs in patients with diabetes, which is a common background disease in patients with ischemic heart diseases, yielded modest results, suggesting the compromised cell functions.   Hypothesis:  Therefore, we hypothesized that, impaired functional benefits of diabetic EPCs are due to altered exosomal contents and whether modulation of identified targets like specific microRNAs in exosomal cargo can rescue and/or enhance their reparative properties.   Methods:  To evaluate this, we isolated Exo from db+ and db/db EPCs and compared their functions in terms of cell survival and angiogenic capacity  in vitro . Further, we injected both db+ and db/db EPC exosomes in db+ mouse models of MI and compared their repair ability  in vivo .   Results:  We report that, db+ EPC-exosomes (Exo) transplantation post-MI significantly improved db+ Exo-mediated post-infarct repair, neovascularization and LV functions. Whereas transplantation of db/db EPC-exosomes worsened heart function. Our in vitro studies revealed that db+ EPC-Exo treatment enhanced tube formation and inhibited apoptosis of human umbilical vein endothelial cells; whereas db/db EPC-Exo exhibited opposite effects, suggesting that reparative capacity of db/db EPC-Exo is impaired in Exo derived from db/db EPCs. Interestingly our microarray experiments revealed that, human CD34+ cells subjected to hyperglycemic conditions and Exo isolated from db/db mice showed elevated basal levels of miR-142 compared to control. Also functional deficiencies exhibited by db/db exosomes was partially rescued by miR-142 knockdown in db/db EPC-Exo. Knockdown of miR-142 in Exo derived from db/db EPCs enhanced endothelial cell functions in vitro.   Conclusions:  Taken together, our studies for the first time suggest that, modulation of miR-142 in db/db-EPC-exo can enhance its functional benefits and ultimately promote better cardiac repair.
Bacterial Adaptation to the Host's Diet Is a Key Evolutionary Force Shaping Drosophila-Lactobacillus Symbiosis
Authors: Maria Elena Martino, Pauline Joncour, Ryan Leenay, Hugo Gervais, Malay Shah, Sandrine Hughes, Benjamin Gillet, Chase Beisel, François Leulier
Journal: Cell Host & Microbe (2018)

Animal-microbe facultative symbioses play a fundamental role in ecosystem and organismal health. Yet, due to the flexible nature of their association, the selection pressures that act on animals and their facultative symbionts remain elusive. Here we apply experimental evolution to Drosophila melanogaster associated with its growth-promoting symbiont Lactobacillus plantarum, representing a well-established model of facultative symbiosis. We find that the diet of the host, rather than the host itself, is a predominant driving force in the evolution of this symbiosis. Furthermore, we identify a mechanism resulting from the bacterium's adaptation to the diet, which confers growth benefits to the colonized host. Our study reveals that bacterial adaptation to the host's diet may be the foremost step in determining the evolutionary course of a facultative animal-microbe symbiosis.
Abstract 95: Heparan sulfate and glypican-1 mediate renal carcinoma metastasis
Authors: Henry Qazi, Heriberto Moran, Limary M. Cancel, Mariya Mayer, Sylvie Roberge, Peigen Huang, Lance L. Munn, John M. Tarbell
Journal: Cancer Research (2018)

Abstract The surface proteoglycan/glycoprotein layer (glycocalyx) on tumor cells has been associated with cellular functions that can potentially enable invasion and metastasis. In addition, aggressive renal carcinoma cells (SN12L1) with high metastatic potential have enhanced invasion rates compared to low metastatic (SN12C) cells in response to interstitial flow stimuli in vitro. Our previous studies suggest that heparan sulfate (HS) and hyaluronic acid (HA) in the glycocalyx play an important role in this flow mediated mechanotransduction and upregulation of invasive and metastatic potential. In our recent study, SN12L1 cells were genetically modified to suppress HS production by knocking down its synthetic enzyme NDST1. Using modified Boyden chambers with defined interstitial flow, we showed that flow-enhanced invasion is suppressed in HS deficient cells. We also examined two prominent HSPGs on renal carcinoma cells, glypican-1 and syndecan-1, and one prominent HA receptor, CD44. We observed higher glypican-1 levels in flow dependent SN12L1 cells when compared to SN12C cells. Caki-1 (highly metastatic) cells did not display flow-dependent invasion in vitro and did not display elevated glypican-1 compared to low metastatic Caki-2 cells. However, we did observe significantly increased HS, HA, syndecan-1 and CD44 in Caki-1 compared to Caki-2 cells suggesting an alternative mechanism for reported higher metastatic rates in these cells. All of our data are consistent with the hypothesis that glypican-1 is the core protein responsible for flow sensing in metastatic cancer cells. This is also consistent with observations in endothelial cells. To assess the ability of tumor cells to metastasize in vivo, parental or HS knockdown SN12L1 cells expressing fluorescent reporters were injected into kidney capsules in SCID mice. Histological analysis confirmed that there was a large reduction (95%) in metastasis to distant organs by tumors formed from knockdown cells compared to control cells with intact HS. The reduction was even greater (98%) in lungs where most of the metastases from the control cells were observed. The ability of these knockdown cells to invade surrounding tissue was also impaired. The substantial inhibition of metastasis and invasion upon reduction of HS suggests an active role for the tumor cell glycocalyx and glypican-1 in tumor progression. Citation Format: Henry Qazi, Heriberto Moran, Limary M. Cancel, Mariya Mayer, Sylvie Roberge, Peigen Huang, Lance L. Munn, John M. Tarbell. Heparan sulfate and glypican-1 mediate renal carcinoma metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 95.
Abstract 3314: Heritable methylation marks associated with prostate and breast cancer risk
Authors: Melissa C. Southey, Jihoon E. Joo, James G. Dowty, Roger L. Milne, EE Ming Wong, Pierre-Antoine Dugué, Dallas English, John L. Hopper, David E. Goldgar, Graham G. Giles
Journal: Cancer Research (2018)

Abstract While most epigenetic marks are reprogrammed during early embryogenesis, some studies have reported Mendelian-like inheritance of germline DNA methylation in particular in cancer susceptibility genes. For instance, individuals with MLH1 silenced throughout the soma fit the clinical criteria for hereditary nonpolyposis colorectal cancer that is indistinguishable from the syndrome resulting from germline mutations in MLH1. Research using multiple-case breast cancer families has shown that LINE-1 and Sat2 DNA methylation levels are lower in individuals with a strong family history. Family clustering of cancer could therefore be due to epigenetic as well as genetic and shared environmental factors. We have recently identified heritable methylation marks associated with breast and/or prostate cancer susceptibility by conducting a study involving 45 Australian multi-generational families with multiple cases of breast or prostate cancer who are not known to carry genetic mutations in cancer susceptibility genes. We developed and applied a new statistical method to identify heritable methylation marks based on complex segregation analysis and identified 24 and 41 methylation marks significantly associated with breast and prostate cancer risk respectively. Several marks across VTRNA2-1, a gene located in a differentially methylated region that is involved in imprinting and shows allele-specific methylation, were associated with heritable risk of both cancer types. A proportion of all identified marks were found to be associated with cancer risk in independent nested case-control studies (ie outside of the multiple-case family setting). We are expanding these successful studies to include additional families and to estimate HRs and age-specific cumulative risks of cancer associated with these marks to enable the incorporation of this information into clinical tools for risk prediction. Citation Format: Melissa C. Southey, Jihoon E. Joo, James G. Dowty, Roger L. Milne, EE Ming Wong, Pierre-Antoine Dugué, Dallas English, John L. Hopper, David E. Goldgar, Graham G. Giles. Heritable methylation marks associated with prostate and breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3314.
Abstract 3216: H2AX is a novel prognostic marker of breast cancer
Authors: Eriko Katsuta, Mutsuko Ouchi, Toru Ouchi, Kazuaki Takabe
Journal: Cancer Research (2018)

Abstract INTRODUCTION: Phosphorylation of histone variant H2AX, termed gamma-H2AX, is well known for its role in DNA damage repair. On the other hand, clinical relevance of expression of H2AX in breast cancer remains to be elucidated. Previously we found that H2AX determines clonogenic cell survival under metabolic oxidative stress and cellular levels of Reactive Oxygen Species (ROS). In this study, we investigated the impact of H2AX expression on breast cancer patients' survival, as well as underlying mechanisms. METHODS: Breast cancer patients in The Cancer Genome Atlas (TCGA) dataset were classified as either high or low expression of H2AX. Overall Survival (OS) and Disease-Free Survival (DFS) as well as Gene Set Enrichment were compared between these two groups. Gene expression of each cell lines was analyzed by RNA-seq. Radiation sensitivity was quantified using cells from patient-derived xenograft (PDX). Gene expression level after neoadjuvant chemo-radio therapy was compared using publically available database (GSE25113). RESULTS: H2AX expression level is higher in triple negative breast cancers (TNBC) than non-TNBC (p&amp;lt;0.001) and in HER2 positive tumors than negative tumors (p=0.048) as well as advanced Stage tumors (Stage I vs Stage II/III/IV, p=0.029). H2AX high expressing tumors showed significantly worse OS (p=0.007) as well as DFS (p=0.001) and this was the case only in advanced Stage tumors (Stage I vs Stage II/III/IV, p=0.029). There were more H2AX high tumors with advancement of Stage (Stage I: 2.8%, Stage II: 5.5%, Stage III/IV 7.4%). In agreement, breast cancer cell line clones that develop metastasis expressed higher H2AX compared from their parental cells (4T1 vs 4T1.2; p&amp;lt;0.001, MDA-MB-231 vs LM2-4; p=0.042). Gene Set Enrichment Analysis (GSEA) demonstrated that not only DNA repair (p&amp;lt;0.001) and ROS related gene set (p=0.011), but also Myc target related gene sets (p=0.002) as well as UV response related gene set (p&amp;lt;0.001) were significantly enriched in H2AX high patients. We also demonstrated that H2AX high expressing cells from PDX showed significantly higher sensitivity to radiation therapy with higher ROS production. Indeed, tumors that demonstrated pathological completely response (pCR) after neoadjuvant chemo-radiation therapy had a trend to have higher H2AX levels compared to non-pCR tumors (p=0.093). CONCLUSIONS: Advanced Stage breast cancers that express high levels of H2AX associated with worse OS and DFS, but showed higher sensitivity to radiation. H2AX can be a prognostic biomarker for recurrent tumor that may be sensitive to radiation therapy. Citation Format: Eriko Katsuta, Mutsuko Ouchi, Toru Ouchi, Kazuaki Takabe. H2AX is a novel prognostic marker of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3216.
Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer
Authors: Maha Hussain, Karim Fizazi, Fred Saad, Per Rathenborg, Neal Shore, Ubirajara Ferreira, Petro Ivashchenko, Eren Demirhan, Katharina Modelska, De Phung, Andrew Krivoshik, Cora N. Sternberg
Journal: New England Journal of Medicine (2018)

Men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising prostate-specific antigen (PSA) level are at high risk for metastasis. We hypothesized that enzalutamide, which prolongs overall survival among patients with metastatic, castration-resistant prostate cancer, would delay metastasis in men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level.