tbuckley/cabot-search huggingface dataset:
Trends in Rates of Infections Requiring Hospitalization Among Adults With Versus Without Diabetes in the U.S., 2000–2015
Authors: Jessica L. Harding, Stephen R. Benoit, Edward W. Gregg, Meda E. Pavkov, Leigh Perreault
Journal: Diabetes Care (2019)

Vascular complications of diabetes have declined substantially over the past 20 years. However, the impact of modern medical treatments on infectious diseases in people with diabetes remains unknown.We estimated rates of infections requiring hospitalizations in adults (≥18 years) with versus without diabetes, using the 2000-2015 National Inpatient Sample and the National Health Interview Surveys. Annual age-standardized and age-specific hospitalization rates in groups with and without diabetes were stratified by infection type. Trends were assessed using Joinpoint regression with the annual percentage change (Δ%/year) reported.In 2015, hospitalization rates remained almost four times as high in adults with versus without diabetes (rate ratio 3.8 [95% CI 3.8-3.8]) and as much as 15.7 times as high, depending on infection type. Overall, between 2000 and 2015, rates of hospitalizations increased from 63.1 to 68.7 per 1,000 persons in adults with diabetes and from 15.5 to 16.3 in adults without diabetes. However, from 2008, rates declined 7.9% in adults without diabetes (from 17.7 to 16.3 per 1,000 persons; Δ%/year -1.5, P < 0.01), while no significant decline was noted in adults with diabetes. The lack of decline in adults with diabetes in the later period was driven by significant increases in rates of foot infections and cellulitis as well as by lack of decline for pneumonia and postoperative wound infections in young adults with diabetes.Findings from this study highlight the need for greater infectious risk mitigation in adults with diabetes, especially young adults with diabetes.
Abstract 156: Endogenous Cardiomyocyte Dedifferentiation and Cycling Revealed by Single-Cell Imaging and Single-Nucleus Transcriptomic Analysis
Authors: Yiqiang Zhang, Nuria Gago-Lopez, Ning Li, Zhenhe Zhang, Naima Alver, William R MacLellan
Journal: Circulation Research (2019)

Although the mammalian heart had been recognized as a post-mitotic non-regenerative organ, recent evidence demonstrated a measurable cardiomyocyte (CM) renewal at low rates in normal hearts and augmented in post-injury myocardium. However, the resources and cellular processes of such a new CM formation, and the underlying molecular programs remained largely undetermined. While CMs in neonatal hearts or adult CMs in tissue culture can undergo (partial) dedifferentiation and proliferation, the roles of in vivo CM dedifferentiation and cycling were unclear. Here, we report a multi-reporter transgenic mouse models featuring efficient adult CM (ACM) genetic cell fate mapping and real-time CM dedifferentiation reporting. In this triple-transgenic model, upon tamoxifen-induced gene recombination, only ACMs switched from expressing red fluorescent protein (RFP) to green fluorescent protein (GFP), and non-CMs remained expressing RFP. The nuclear blue fluorescent protein (BFP) signal was expressed in normal mature ACMs but reduced in neonatal or cultured dedifferentiated ACMs. Hence, all 4 plausible modes of new CM formation can be visualized using this model. Using ImageStream for single-cell imaging analysis, we demonstrated that non-myocytes (including putative cardiac progenitor cells) contributed negligibly to new ACM formation at baseline or after myocardial infarction (MI). In contrast, there was a significant increase in dedifferentiated (e.g. GFP + BFP - ) CMs in post-MI hearts compared to the sham. Cell cycling activity was enhanced within the dedifferentiated CM population compared to normal ACMs (GFP + BFP + ). Furthermore, we applied massive whole-heart single-nucleus RNA-seq to dissect the transcriptomes of dedifferentiated CMs. We found that CMs in post-MI hearts identified with dedifferentiation reporter had significant down-regulations of genes in networks for hypertrophic growth, cardiac contractile functions and metabolism, but up-regulation in signaling pathways for cell survival, active cell cycle and proliferation. Therefore, cellular dedifferentiation may be an important prerequisite for endogenous CM cell cycling and proliferation and explain the measurable cardiac myogenesis seen after MI.
Abstract 130: Development of Bioinspired Synthetic Exosomes With Proangiogenic Potential
Authors: Sezin Aday, Inbal Halevy, Maryam Anwar, Paolo Madeddu, Susmita Sahoo, Enrico Petretto, Dan Peer, Costanza Emanueli
Journal: Circulation Research (2019)

Exosomes with variable microRNA cargos are released from different cell types and stimulate angiogenesis in animal models. Therefore, exosomes are currently considered for their potential to represent a safer and easier biological-based alternative to stem cell therapies. However, the limited amount of exosomes that can be reproducibly prepared from cultured stem cells and the complexity of the cargo of endogenous exosomes make them difficult to develop as off-the-shelf “pharmaceutical products” and limit their clinical potential. These issues could be surpassed by the use of artificial (i.e. nanoparticles mimicking the natural product) exosomes carrying a therapeutic cargo. In consideration of the possibility that not all cargo components of exosomes are required for their therapeutic functions, we reasoned that bioinspired artificial exosomes (AEs) incorporating key therapeutically relevant molecules and devoid of potentially negative or indifferent factors could further improve their therapeutic potential. Therefore, we developed and tested AEs containing exosomal proangiogenic miRNAs as a “proof-of-concept” for therapeutic angiogenesis. In order to achieve this, we: (1) characterized the common microRNA cargo of endogenous proangiogenic exosomes (from stem cells, pericytes and pericardial fluid) using bioinformatics, (2) exploited this knowledge to develop off-the-shelf artificial exosomes (AEs) with proangiogenic capacities, (3) validated the angiogenic potential of the bioinspired AEs. Bioinformatics analyses integrating data of miRNA arrays and panels of proangiogenic exosomes confirmed the enrichment of let-7 family in these exosomes. After testing the angiogenic potential of different members of let-7 family, we produced AEs containing let-7b (the most potent in the family) by microfluidic micromixing. The AEs were uptaken by human ECs cultured under hypoxic conditions, without causing toxicity. let-7b-AEs transferred functional let-7b, thus decreased the expression of validated targets of let-7b in recipient cells. let-7b-AEs improved EC survival, proliferation and angiogenesis in vitro and in vivo . These data suggest the therapeutic potential of bioinspired AEs containing let-7b.
Central Nervous System Complications after Allogeneic Hematopoietic Stem Cell Transplantation: The Role of Calcineurin Inhibitors
Authors: Elisa Sala, Stephanie von Harsdorf, Verena Wais, Thanh Mai Anne Nguyen, Raphael Beck, Hartmut Döhner, Donald Bunjes, Florian Kuchenbauer
Journal: Blood (2018)
Re: Campochiaro et al.: The Port Delivery System with ranibizumab for neovascular age-related macular degeneration: results from the randomized phase 2 Ladder clinical trial (Ophthalmology. 2019;126:1141-1154)
Authors: Ashish Sharma, Nilesh Kumar, Baruch D. Kuppermann, Bandello Francesco
Journal: Ophthalmology (2019)
Clinical Features and Outcome of Newly Diagnosed, Symptomatic Patients with Multiple Myeloma ≥80 Years of Age: An Analysis of the Greek Myeloma Study Group
Authors: Meletios Athanasios Dimopoulos, Efstathios Kastritis, Sosana Delimpasi, Eirini Katodritou, Eleftheria Hatzimichael, Marie-Christine Kyrtsonis, Panagiotis Repousis, Maria Tsirogianni, Zafiris Kartasis, Agapi Parcharidou, Michalis Michael, Eurydiki Michalis, Dimitra Gika, Argiris Symeonidis, Evangelos Terpos, Konstantinos Zervas
Journal: Blood (2011)
Abstract 466: Myopathy Causing Bag3 <sup>P209L</sup> Protein Leads to Restrictive Cardiomyopathy Caused by Aggregate Formation and Sarcomere Disruption in Cardiomyocytes
Authors: Kathrin Graf-Riesen, Kenichi Kimura, Andreas Unger, Achim Lother, Lutz Hein, Jan Daerr, Julia Braune, Astrid Ooms, Guang Li, Sean M. Wu, Jörg Höhfeld, Wolfgang A. Linke, Dieter Fürst, Bernd K. Fleischmann, Michael Hesse
Journal: Circulation Research (2019)

The co-chaperone BAG3 (Bcl-2 associated athanogene 3) is strongly expressed in cross-striated muscles and plays a key role in the turnover of muscle-proteins as a member of the CASA (chaperone-assisted selected autophagy) complex. An amino acid exchange (P209L) in the human BAG3 gene, caused by a single base mutation, gives rise to a severe dominant childhood muscular dystrophy, restrictive cardiomyopathy, and respiratory insufficiency. To get deeper insights into the pathophysiological mechanisms of the disease, we generated a transgenic mouse model of the human mutation BAG3 P209L , in which a fusion protein consisting of the human BAG3 P209L and the green fluorescent protein eGFP can be conditionally overexpressed. Ubiquitous overexpression of BAG3 P209L -eGFP leads to a severe phenotype between the second and fourth week of life, including decreased body weight, skeletal muscle weakness, and heart failure. Echocardiography revealed that the BAG3 P209L -mice suffer from restrictive cardiomyopathy and Sirius-red-staining of heart tissue showed extensive fibrosis. In cardiomyocytes, isolated from hearts of transgenic mice overexpressing BAG3 wt -eGFP or BAG3 P209L -eGFP, BAG3 wt -eGFP stringently localizes to sarcomeres and intercalated discs, whereas cardiomyocytes from BAG3 P209L -eGFP mice displayed formation of BAG3 containing aggregates and disruption of sarcomeres in vivo . While BAG3 P209L -eGFP binding to á-Hsp70, Filamin C and á-HspB8 was unchanged it was less soluble than BAG3 and had a tendency to aggregate, thereby sequestering BAG3 and its clients. Depletion of the BAG3 pool leads to an impairment of CASA and accumulation of damaged proteins, causing sarcomere disintegration leading to restrictive cardiomyopathy.
AYA ALL: Real World Experience from a Tertiary Care Center in North India
Authors: Satyaranjan Das, Uday Yanamandra, Mir Moslem, Rajan Kapoor, Suman Pramanik, Rajiv Kumar, Harshit Khurana, Sanjeevan Sharma, Tarun Verma, Singh Jasjit, Ajay Sharma, Velu Nair
Journal: Blood (2018)
Genetic Variation in Genes That Regulate T-Cell Differentiation and Function Is Associated with An Increased Risk of Developing B-Cell Non- Hodgkin Lymphoma
Authors: Stephen M. Ansell, Anne Novak, Zhi-Zhang Yang, Zachary S. Fredericksen, Alice H. Wang, Neil Kay, Mark Liebow, Ahmet Dogan, Timothy G. Call, Thomas Witzig, Thomas M. Habermann, Susan L. Slager, James R. Cerhan
Journal: Blood (2008)
Sirolimus Augments Hematopoietic Stem and Progenitor Cell Recovery from Hematopoietic Stress
Authors: Xingmin Feng, Zenghua Lin, Maile K. Hollinger, Wanling Sun, Zhijie Wu, Kaylind Batey, Keyvan Keyvanfar, Jichun Chen, Neal S. Young
Journal: Blood (2018)
Exploring and supporting older women’s chemotherapy decision-making in early-stage breast cancer.
Authors: Meghan Sri Karuturi, Ashley Housten, Sharon H. Giordano, Diana Hoover, Robert Joseph Volk
Journal: Journal of Clinical Oncology (2019)

181 Background: Few studies have focused on the therapeutic decision-making process in older adults with cancer. This study sought to address this gap by exploring older adult breast cancer patients’ (pts) perspectives on neo/adjuvant chemotherapy, thereby identifying informational needs as they navigate the decision-making process. Methods: Women ≥65 years diagnosed with early stage (I-III) breast cancer were recruited from an academic center following their decision on whether to receive neo/adjuvant chemotherapy. Pts took part in individual semi-structured interviews to explore their perspectives, knowledge, and values. They also completed surveys assessing sociodemographics, health literacy/numeracy, and shared decision-making (SDM-Q-9). Interviews were audio-recorded and transcribed, and analyzed using the Sort and Sift, Think and Shift qualitative approach. Quantitative data was summarized using descriptive statistics. Results: 26 pts completed interviews (age range 65-92; 81% non-Hispanic White; 81% ≥ college degree; 70% single). 14 pts elected to undergo chemotherapy and 11 declined. Most pts had adequate health literacy (mean = 4.31; SD = 1.1 on Single Item Literacy Scale) and numeracy (mean = 4.4; SD = 1.0 on Single Item Numeracy Scale). Pts scored high on the shared decision-making questionnaires (SDM-Q-9, mean = 5.3, SD = 0.7). Thematic analysis uncovered several commonalities regardless of the decision. Pts sought information regarding their disease/treatment, but in some instances were confused regarding the objective of chemotherapy. They often chose treatment outside of the physician’s recommendation, and referenced the subjective experience of friends/family members with cancer. Self-perception of health and the side-effects of chemotherapy were also key factors. Pts also placed importance on the maintenance of quality of life throughout the treatment trajectory. Conclusions: Decision-making strategies in older patients were shaped by knowledge, values and the anectodal experience of others. These discussions will subsequently shape the creation of a decision support tool for older pts and physicians to better facilitate the shared-decision making process.
Impact of dual-eligible status on survival in Medicare patients with lung cancer.
Authors: Meera Vimala Ragavan, Rebecca Gardner, Kristen Cunanan, Vandana Sundaram, Heather A. Wakelee, Summer S. Han
Journal: Journal of Clinical Oncology (2019)

149 Background: Dual-eligible (DE) patients are insured by both Medicaid and Medicare and are known to have complex medical and social needs. While DE patients with cancer have been shown to be less likely to undergo definitive surgical resection of early stage disease and more likely to be diagnosed at a later stage, they have also been shown to be more likely to adhere to cancer treatment due to lower copays with Medicaid. Lung cancer (LC) is the most common cancer diagnosed in the DE population, but little is known about the outcomes of DE patients with LC compared to non-DE patients. Our study sought to assess the impact of DE status on overall survival in lung cancer patients. Methods: We conducted a cross-sectional secondary analysis of data extracted from the Medicare-SEER database, including Medicare patients diagnosed with LC where complete survival data was available. Patients were defined as “DE” if they were designated as DE status during the month they were diagnosed with LC. Categorical variables were compared between DE and non-DE patients using the chi2 test. A Cox regression analysis was performed to evaluate the association between mortality and dual-eligibility, adjusting for demographic and clinical factors including age, ethnicity, gender, stage at time of diagnosis, type of lung cancer, and place of residence (urban vs. rural). Results: A total of 118,816 patients were included in the analysis, of which 81% were non-DE and 19% were DE. DE patients were more likely than non-DE patients to be female, non-white, younger, have squamous cell carcinoma, and be diagnosed at a later stage (P-values all &lt; 0.001). After adjusting for all demographic and clinical characteristics included in the analysis, the hazard ratio for mortality was 1.243 (95% confidence interval: 1.222-1.264, p &lt; 0.001) for DE patients compared to non-DE patients. Conclusions: DE patients with LC have a significantly higher mortality rate than non-DE patients in the Medicare population after adjusting for confounding factors. Future studies should explore the factors that influence this survival differential and consider targeted interventions at the policy level to improve outcomes in this population.
Abstract 325: Characterization of Circular RNAs in Vascular Smooth Muscle Cells With Vascular Calcification
Authors: Hyun Kook, Juhee Ryu, Geon Jeong, Yeong-Hwan Lim, Duk-Hwa Kwon, Nakwon Choe, Sera Shin, Yongsook Kim, Youngkeun Ahn, Young-Kook Kim
Journal: Circulation Research (2019)

Circular RNAs (circRNAs) are generally formed by back splicing, and are expressed in various cells. Vascular calcification, a common complication of chronic kidney disease, is often associated with cardiovascular disease. The relationship between circRNAs and vascular calcification has not yet been studied. Inorganic phosphate was used to treat rat vascular smooth muscle cells to induce vascular calcification. CircRNAs were identified by analyzing RNA sequencing data, and their expression change during vascular calcification was validated. The selected circRNAs, including circSamd4a, circSmoc1-1, circMettl9, and circUxs1 were resistant to RNase R digestion, and mostly localized in the cytoplasm. Silencing circSamd4a promoted vascular calcification, while overexpressing it reduced vascular calcification. In addition, microRNA (miRNA) microarray and luciferase reporter assay suggested that circSamd4a could act as miRNA suppressor. Our data shows that circSamd4a have anti-calcification roles by functioning as miRNA sponges. Since circSamd4a is conserved in humans, they can serve as novel therapeutic targets in resolving vascular calcification.
Correcting the Conclusion in a Study of Frameworks for Measurement of Absolute or Clinical Benefit—In Reply
Authors: Ronak Saluja, Matthew Cheung, Kelvin K. W. Chan
Journal: JAMA Oncology (2019)

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Reducing ED visits by “closing the loop” for symptomatic patients.
Authors: Edward Arrowsmith, Lenes Suits, Bertrand Marquess Anz, Gina Geren, Leslie Vasta, Aaron J. Lyss
Journal: Journal of Clinical Oncology (2019)

100 Background: Improving the value provided to patients and payers in our system of cancer care relies on reduction of avoidable hospital and emergency department (ED) utilization. Furthermore, recent payer pressures on community oncology practices (COPs) have resulted in an increased focus on improving care coordination (CC) under strict resource constraints. As part of the ASCO Quality Training Program, we tested several low-cost CC interventions, leveraging workflow redesign, already employed care team members, and technology already implemented, to reduce ED visits (EDV) in a single large COP clinic where more than 3,200 cancer patients were treated during 2016. Methods: Baseline EDV rates were obtained through nurse chart review during Jan.-Jun. 2016. The following CC interventions were implemented: Initiated after hours call process with access to EMR and patient access to bidirectional real-time messaging with care team members; Implemented new in-office process to “close the loop” on patient evaluations by creating follow up guidelines for symptomatic telephone triage and in-clinic patient evaluations; Implemented a standard 48 hour follow up process for all EDV and hospital admissions; Increased patient awareness of telephone triage services during and after clinic hours by: augmenting new patient education by staff, developing a magnetic reminder to call the office for non-emergent and emergency situations, and instructions for use of afterhours call system. Nurse chart reviews were conducted throughout implementation to observe effects of new CC processes on EDV. Results: We observed a 30% reduction in EDV from baseline measurement. No new FTEs added and no new technology licenses acquired for this initiative. Conclusions: Low-cost CC interventions can be implemented in COPs to avoid ED utilization. Limitations of this analysis included manual chart abstraction that could not account for EDV outside the partnering health system, illustrating data access for hospital utilization remains a major challenge for quality improvement efforts for COPs. Additional challenges have been experienced in expanding these process improvements from a single large clinic to the broader Tennessee Oncology network of more than 30 clinics.
Abstract 577: Matricryptin p1158/59 Improves Cardiac Function Post-myocardial Infarction by Reducing Adverse Remodeling
Authors: Gabriel A Grilo, Patti R Shaver, Rugmani P Iyer, Lisandra E de Castro Brás
Journal: Circulation Research (2019)

Matricryptins are biologically active peptides, generated from extracellular matrix proteolysis, able to regulate cell function and survival. We recently identified a collagen-derived matricryptin (p1158/59) that gradually forms post-myocardial infarction (MI). In humans, p1158/59 plasma levels negatively correlate with left ventricle (LV) filling pressure, indicating that therapeutic elevation of this matricryptin could benefit functional remodeling. Previously, we showed p1158/59 binds to cardiac fibroblasts in vitro to stimulate migration and mice treated with p1158/59 for 7 days post-MI display reduced fibrosis, suggestive of reduced LV remodeling. Our goals were to establish the therapeutic effects of p1158/59 in long term cardiac remodeling and function using a rodent MI model. We used a murine permanent occlusion MI model (male and female C57Bl/6 mice, 4-6 months old, n=6/group) to assess the effects of p1158/59 treatment. Three hours after MI, mice received matricryptin (950 μg/day) or saline solution via an osmotic mini-pump for 28 days (D28). Parameters of cardiac remodeling and function were analyzed by serial echocardiography (D0, D14, D28) and LV remodeling gene arrays. As measured by ejection fraction (EF), matricryptin p1158/59 significantly blunted the reduction in cardiac function observed post-MI (saline 12% EF, p1158/59 31% EF, p=0.004). Additionally, p1158/59 reduced LV dilation displaying decreased end-systolic and end-diastolic volumes compared to controls (ESV p=0.014, EDV p=0.037). Similarly, internal diameter (ID) in diastole and systole were also reduced versus saline (IDd p=0.010, IDs p=0.014). Finally, we observed less tinning of the posterior wall (PW) in p1158/59-treated mice compared to vehicle controls (LVPWd p=0.018, LVPWs p=0.047). These results indicate that p1158/59 attenuated cardiac dysfunction and remodeling post-MI by preserving cardiac compliance and structure. Our data suggest that matricryptin p11/58/59 treatment reduces adverse remodeling post-MI resulting in improved cardiac function.