tbuckley/cabot-search huggingface dataset:
Costs after incident breast cancer diagnosis among high-deductible health plan members.
Authors: James Wharam, Jamie Wallace, Christine Lu, Anita K. Wagner, Stephen Soumerai, Craig Earle, Larissa Nekhlyudov, Dennis Ross-Degnan, Fang Zhang
Journal: Journal of Clinical Oncology (2019)

120 Background: High-deductible health plans (HDHP) are associated with breast cancer treatment delays of up to 10 months, but their impact on health outcomes is unknown. We hypothesized that, compared with women in generous plans, HDHP members would present with more advanced disease and thus experience higher total costs of early care. Methods: We studied 2004-2014 claims data from a large US health insurer. We included women aged 25-64 who were in traditional low-deductible (≤$500) health plans for 1 baseline year then experienced either an employer-mandated switch to HDHPs (≥$1000) for up to 4 or years or an employer-mandated continuation in low deductible plans. We defined the HDHP switch date as the index date. We then restricted to women who developed incident breast cancer after the index date. Using baseline characteristics, we closely matched HDHP members with incident breast cancer to contemporaneous women with incident breast cancer who remained in low-deductible plans. We measured total costs of all health care services in the 60 days after incident breast cancer diagnosis as a proxy for the intensity of incident breast cancer care. We used negative binomial regression adjusted for baseline characteristics to compare total 60-day costs among HDHP and control members. We also subset analyses to low-income women. Results: We included 1514 HDHP members and 9283 matched controls. 60-day costs after incident breast cancer diagnosis were $24,151 (95% CI: $22,766, $25,535) among HDHP members and $22,474 ($21,952, $22,996) among controls, an absolute difference of $1677 ($197, $3156) and a relative difference of 7.5% (8.1%, 14.1%). Low-income HDHP members had corresponding absolute and relative differences of $2653 ($368, $4939) and 12.5% (1.5%, 23.5). Conclusions: HDHP members with incident breast cancer had 7.5% higher health care costs in the 60 days after incident breast cancer than women with more generous coverage, a finding driven 12.5% higher costs among low-income HDHP members. Results raise concerns that delays in breast cancer care among HDHP members are associated with more advanced disease and adverse outcomes.
Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma
Authors: Bin Zhang, Min Min Li, Wen Hui Chen, Jian Fu Zhao, Wei Qi Chen, Yu Hao Dong, Xiao Gong, Qiu Ying Chen, Lu Zhang, Xiao Kai Mo, Xiao Ning Luo, Jie Tian, Shui Xing Zhang
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial. <h3>Objectives</h3> To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach. <h3>Data Sources</h3> PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019. <h3>Study Selection</h3> Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC. <h3>Data Extraction and Synthesis</h3> Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model. <h3>Main Outcomes and Measures</h3> Overall survival (OS), progression-free survival (PFS), distant metastasis–free survival (DMFS), and locoregional recurrence-free survival (LRFS). <h3>Results</h3> A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC. <h3>Conclusions and Relevance</h3> These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.
Abstract 238: Critical Role of Ryanodine Receptor Bound Calmodulin to Prevent Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Yoshihide Nakamura, Takeshi Yamamoto, Shigeki Kobayashi, Masaki Tamitani, Yoriomi Hamada, Go Fukui, Xiaojuan Xu, Shigehiko Nishimura, Takayoshi Kato, Hitoshi Uchinoumi, Tetsuro Oda, Shinichi Okuda, Masafumi Yano
Journal: Circulation Research (2019)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by a single point mutation in the cardiac type 2 ryanodine receptor (RyR2). Using knock-in mouse (KI) model (R2474S/+), we previously reported that a single point mutation within the RyR2 sensitizes the channel to agonists, primarily mediated by defective inter-domain interaction within the RyR2 molecule and subsequent dissociation of calmodulin (CaM) from the RyR2. Here, we examined whether CPVT can be genetically rescued by enhancing the binding affinity of CaM to the RyR2. We first determined whether there is a possible amino-acid substitution at the CaM-binding domain in the RyR2 (3584-3603) that can enhancethe binding affinity of CaM, and found that V3599K substitution showed the highest binding affinity of CaM to CaM-binding domain. Hence, we generated a heterozygous KI mouse model (V3599K/+) with a single amino acid substitution in the CaM-binding domain of the RyR2, and crossbred it with the heterozygous CPVT -associated R2474S/+ KI mouse to obtain a double heterozygous R2474S/V3599K KI mouse. The CPVT phenotypes—bidirectional or polymorphic ventricular tachycardia, spontaneous Ca2+ transients, and Ca2+ sparks—were all inhibited in the R2474S/V3599K mice. Thus, enhancement of the CaM binding affinity of the RyR2 is essential to prevent CPVT-associated arrhythmogenesis.
Whole Genome Association Study in Acute Myeloid Leukemia with a Normal Karyotype, Using a Single-Nucleotide Polymorphism (SNP) Analysis.
Authors: Yongjun Cha, Kwang-Sung Ahn, Juwon Park, Byung-Su Kim, Soo-Mee Bang, In-Ho Kim, Sung-Soo Yoon, Dongsoon Lee, Jong Seok Lee, Young Yiul Lee, Seonyang Park, Byoung Kook Kim
Journal: Blood (2007)
Autologous Stem Cell Transplantation For Multiple Myeloma In Patients Over Age 70: Decision Making, Eligibility, and Preliminary Outcomes
Authors: Aleksandra E Schriber, Gail Sulski, Nicole Thurman, Rochelle Chiffelle, Anthony Szetela, Denise Gibson, Aocns, Abbas Jonathan, Selma Kendrick, Adrienne D. Briggs
Journal: Blood (2013)
Abstract 794: Endothelial Specific Ablation of Estrogen Receptor Alpha Rapid Signaling Revealed Exacerbated Vascular Remodeling Response
Authors: Pangyen Liu, Yukio Hiroi, Kazutaka Ueda, Nobuaki Fukuma, Yuxin Li, Kensuke Noma, James K. Liao
Journal: Circulation Research (2019)

Background: Estrogen exerts complex physiological effects via its rapid (non-genomic) and genomic actions. In particular, rapid signaling of estrogen receptor alpha (ERα) has been implicated in the vasculo-protective effects, in which both endothelial and smooth muscle cells might be involved. However, no prior studies have determined the role of ERα rapid signaling in the endothelium. This study aims to clarify the impact of ERα rapid signaling in the vasculo-protection, using a novel mouse model lacking endotheilal-specific ERα rapid signaling. Methods and Results: In immunoblotting, p85α and pGSK3β, non-genomic pathway downstream signals, were reduced in ERα mutants RR259/260AA with estradiol (E2) stimulation at concentrations of 10 -11 and 10 -10 M . ERE-luciferase assay demonstrated E2 induced genomic pathway activity was preserved even in ERα mutants RR259/260AA. We generated a mouse model in which rapid signaling of ERα was ablated in the endothelium by crossing Tie2-Cre transgenic mice with floxed ERα mutants (RR 259/260 AA) in which p85α and ERα interaction was disrupted. In endothelial cells isolated from ERα KI/KI Tie2 cre/+ animals, E2 at a concentration of 10 -8 M failed to induce phosphorylation of Akt, confirming the absence of ERα rapid signaling. Baseline characteristics at 8 to 12 weeks of age were undistinguishable between the genotypes, including body weight (KI:19.2±0.366 g vs WT: 18.9±0.356 g ) systolic blood pressure (KI:106.1±3.336 vs WT: 103.5±2.133 mmHg) and echocardiographic fractional shortening (KI:54.4±0.751 vs WT: 55.19±0.947 %). We then assessed how vascular remodeling process was impacted in a carotid artery wire injury model. Histological analyses with Elastica van Gieson staining two weeks after induction of injury revealed that wall thickness and area of medial layer composed mainly of smooth muscle cells were significantly increased in ERα KI/KI Tie2 cre/+ mouse, as compared to wild types (KI:44.85±1.948 μm vs WT: 29.32±1.753 μm , KI:42,047±1,560 μm 2 vs WT: 32,815±1,211 μm 2 , respectively ). Conclusions: Our results demonstrate that the rapid signaling of ERα in the endothelium critically regulates vascular smooth muscle cell growth after vascular injury, suggesting the essential role to vascular remodeling.
Jadenu Substituting Exjade in Beta Thalassemia Major (BTM) Patients with Iron Overload: Effect on Serum Ferritin Concentration, Liver Iron Content and Biochemical Profiles
Authors: Mohamed A Yassin, Abdulqadir Nashwan, Nancy Kassem, Ashraf Tawfiq Soliman, Vincenzo De Sanctis, Ahmed A Adel, Radwa M Hussein, Ahmed Basha, Randa Al -Okka, Rula Ghasoub
Journal: Blood (2018)
Comparative Efficacy of Interventions for Aggressive and Agitated Behaviors in Dementia
Authors: Jennifer A. Watt, Zahra Goodarzi, Areti Angeliki Veroniki, Vera Nincic, Paul A. Khan, Marco Ghassemi, Yuan Thompson, Andrea C. Tricco, Sharon E. Straus
Journal: Annals of Internal Medicine (2019)

Both pharmacologic and nonpharmacologic interventions are used to treat neuropsychiatric symptoms in persons with dementia.To summarize the comparative efficacy of pharmacologic and nonpharmacologic interventions for treating aggression and agitation in adults with dementia.MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO between inception and 28 May 2019 without language restrictions; gray literature; and reference lists scanned from selected studies and systematic reviews.Randomized controlled trials comparing interventions for treating aggression and agitation in adults with dementia.Pairs of reviewers independently screened studies, abstracted data, and appraised risk of bias.After screening of 19 684 citations, 163 studies (23 143 patients) were included in network meta-analyses. Analysis of interventions targeting aggression and agitation (148 studies [21 686 patients]) showed that multidisciplinary care (standardized mean difference [SMD], -0.5 [95% credible interval {CrI}, -0.99 to -0.01]), massage and touch therapy (SMD, -0.75 [CrI, -1.12 to -0.38]), and music combined with massage and touch therapy (SMD, -0.91 [CrI, -1.75 to -0.07]) were clinically more efficacious than usual care. Recreation therapy (SMD, -0.29 [CrI, -0.57 to -0.01]) was statistically but not clinically more efficacious than usual care.Forty-six percent of studies were at high risk of bias because of missing outcome data. Harms and costs of therapies were not evaluated.Nonpharmacologic interventions seemed to be more efficacious than pharmacologic interventions for reducing aggression and agitation in adults with dementia.Alberta Health Services Critical Care Strategic Clinical Network. (PROSPERO: CRD42017050130).
Use of All Trans Retnoic Acid (ATRA) Via Nasogastric Tube (NGT) in Patients Unable to Swallow in Treatment of Acute Promyelocytic Leukemia (APL): A Case Series
Authors: Mohan Preet, Gurinder Sidhu, Rajnish Khillan, Marc Silbergleit, Albert S. Braverman, Ratesh Khillan
Journal: Blood (2011)
Phase II study of R–CVP followed by rituximab maintenance therapy for patients with advanced marginal zone lymphoma: consortium for improving survival of lymphoma (CISL) study
Authors: Sung Yong Oh, Won Seog Kim, Jin Seok Kim, Seok Jin Kim, Dok Hyun Yoon, Deok‐Hwan Yang, Won Sik Lee, Hyo Jung Kim, Ho‐Young Yhim, Seong Hyun Jeong, Jong Ho Won, Suee Lee, Jee Hyun Kong, Sung‐Nam Lim, Jun Ho Ji, Kyung A. Kwon, Gyeong‐Won Lee, Jae Hoon Lee, Ho Sup Lee, Ho‐Jin Shin, Cheolwon Suh
Journal: Cancer Communications (2019)

Abstract Background The response rate and survival improvement for rituximab, a CD20‐targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single‐arm, open‐label phase II study evaluated the survival efficacy of 2 years of rituximab‐maintenance therapy in patients with stage III–IV CD20‐positive MZL who had responded to first‐line R–CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R–CVP warrants further investigation. Methods Prior to rituximab‐maintenance therapy, patients received 6–8 cycles of first‐line R–CVP therapy for stage III–IV MZL. Rituximab (375 mg/m 2 ), cyclophosphamide (750 mg/m 2 ), and vincristine (1.4 mg/m 2 ; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3‐week cycle, while oral prednisolone (100 mg) was given on days 1–5 of each 3‐week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R–CVP treatment, were prescribed rituximab‐maintenance therapy which was administered intravenously at a dose of 375 mg/m 2 every 8 weeks for up to 12 cycles. The primary endpoint was progression‐free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety. Results 47 patients were enrolled, of whom, 45 (96%) received rituximab‐maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R–CVP first‐line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow‐up of 38.2 months, their observed 3‐year PFS rate was 81%. During the rituximab‐maintenance, 6 PR and 1 SD patients achieved CR following the administration of R–CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS ( P = 0.003) and demonstrated a 3‐year OS rate of 90%. Rituximab‐maintenance therapy was well tolerated, and the common treatment‐emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%). Conclusion Rituximab‐maintenance therapy following first‐line R–CVP demonstrated good PFS in patients with stage III–IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov : NCT01213095
Effective mRNA pulmonary delivery by dry powder formulation of PEGylated synthetic KL4 peptide
Authors: Yingshan Qiu, Rico C.H. Man, Qiuying Liao, Keshia L.K. Kung, Michael Y.T. Chow, Jenny K.W. Lam
Journal: Journal of Controlled Release (2019)

Pulmonary delivery of messenger RNA (mRNA) has considerable potential as therapy or vaccine for a range of lung diseases. Inhaled dry powder formulation of mRNA is particularly attractive as it has superior stability and dry powder inhaler is relatively easy to use. A safe and effective mRNA delivery vector as well as a suitable particle engineering method are required to produce a dry powder formulation that is respirable and mediates robust transfection in the lung. Here, we introduce a novel RNA delivery vector, PEG12KL4, in which the synthetic cationic KL4 peptide is attached to a monodisperse linear PEG of 12-mers. The PEG12KL4 formed nano-sized complexes with mRNA at 10:1 ratio (w/w) and mediated effective transfection on human lung epithelial cells. PEG12KL4/mRNA complexes were successfully formulated into dry powder by spray drying (SD) and spray freeze drying (SFD) techniques. Both SD and SFD powder exhibited satisfactory aerosol properties for inhalation. More importantly, the biological activity of the PEG12KL4 /mRNA complexes were successfully preserved after drying. Using luciferase mRNA, the intratracheal administration of the liquid or powder aerosol of PEG12KL4 /mRNA complexes at a dose of 5 μg mRNA resulted in luciferase expression in the deep lung region of mice 24 h post-transfection. The transfection efficiency was superior to naked mRNA or lipoplexes (Lipofectamine 2000), in which luciferase expression was weaker and restricted to the tracheal region only. There was no sign of inflammatory response or toxicity of the PEG12KL4 /mRNA complexes after single intratracheal administration. Overall, PEG12KL4 is an excellent mRNA transfection agent for pulmonary delivery. This is also the first study that successfully demonstrates the preparation of inhalable dry powder mRNA formulations with in vivo transfection efficiency, showing the great promise of PEG12KL4 peptide as a mRNA delivery vector candidate for clinical applications.
Positive Stool Cultures Could Predict the Clinical Outcomes of Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Lijuan Hu, Qi Wang, Xiaohui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Kaiyan Liu, Hui Wang, Xiaojun Huang, Xiao-Dong Mo
Journal: Blood (2018)
Increased Survival and Migration of CLL B-Cells in the Presence of Marrow Mesenchymal Stromal Cells: Novel Findings for Microenvironment-Targeted Therapies
Authors: Elisa Ave, Federica Frezzato, Cristina Gattazzo, Valentina Trimarco, Veronica Martini, Andrea Visentin, Monica Castelli, Samuela Carraro, Federica Lessi, Anna Cabrelle, Monica Facco, Gianpietro Semenzato, Livio Trentin
Journal: Blood (2012)
Clinical Relevance Of Cachexia Assessed By An Anthropometric Tool In Elderly Patients With Diffuse Large B-Cell Lymphoma Treated By Immunochemotherapy
Authors: Helene Lanic, Jerome Kraut, Romain Modzelewski, Florian Clatot, Jean-Michel Picquenot, Nathalie Contentin, Pascal Lenain, Luminata Groza, Emilie Lemasle, Carole Fronville, Nathalie Cardinael, Marie-Laure Fontoura, Chamseddine Ali, Oana Brehar, Aspasia Stamatoullas, Stéphane Lepretre, Herve Tilly, Fabrice Jardin
Journal: Blood (2013)
Abstract 885: The Role of Paraoxonase 2 (PON2) in Mitochondrial Membrane Phospholipid Composition and Lipid Peroxidation
Authors: Dawoud Sulaiman, Jeremy C Papesh, David Meriwether, Srinivasa T Reddy
Journal: Circulation Research (2019)

Introduction: We have recently reported that PON2 plays a protective role against myocardial ischemia-reperfusion injury (IRI) by reducing oxidative stress and mitochondrial dysfunction, in the form of improved calcium retention capacity and integrity of the mitochondrial membrane potential. It is known that mitochondrial phospholipids (PL) play critical roles in mitochondrial homeostasis via maintenance of normal bioenergetics and membrane function. These PLs undergo oxidative stress during IRI resulting in an increase in lipid peroxidation, damage of the respiratory complexes and loss of mitochondrial membrane potential. Hypothesis: PON2 protects cardiomyocytes against myocardial IRI by modulating the mitochondrial membrane phospholipid composition and lipid peroxidation. Methods: Two methods were developed to measure 1) various oxidized lipid species (i.e. 5, 12, and 15 HETE, 9, 13 HODE, and 5-oxoETE) and inflammatory markers (lipid panel) and 2) a panel of phospholipid species (i.e. PC, PE, PS) (PLP) via mass spectrometry (ESI LC-MS/MS). Mitochondria were isolated from male C57BL6/J (WT) and PON2 deficient (PON2-def) mice. PLs were then extracted using a modified Bligh and Dyer method with the respective internal standards, and run on a SCIEX 5500 QTrap run in negative ion mode and controlled by Analyst 1.6.2 software. Data is expressed as mean±SEM. Student’s T-test is used for statistical analysis, with p&lt;0.05 considered statistically significant. Results: We determined that under baseline conditions, PON2-deficient mice have altered mitochondrial membrane PL composition and lipid peroxidation. We observe that PON2-def mitochondria have a significant decrease in various phosphatidylcholine species and an increase in phosphatidylethanolamine (42:9). In addition, there were variations in the composition of phosphatidylserine and phosphatidylinositol. The alteration of mitochondrial PL were accompanied by significant increases in various oxidized lipids including 9, 13-HODE, 14S, 17S-HDHA, 5, 15-HETE, and 5-oxoETE. Conclusion: Our preliminary studies point to the important role that PON2 plays in modulating mitochondrial PL composition and lipid peroxidation, and warrant further investigation under myocardial IRI.
Oxidative Modified Fibrinogen in Cardiovascular Diseases
Authors: Jana Štikarová, Jiri Suttnar, Zofie Sovova, Eliska Ceznerova, Jaromir Novak, Jan Louzil, Roman Kotlín, Pavla Roselova, Jirina Kaufmanova, Leona Chrastinova, Alzbeta Hlavackova, Pavel Majek, Ondrej Kucerka, Martin Hajsl, Martin Maly, Jan E. Dyr
Journal: Blood (2018)
Multi-Dimensional Analysis of Immune Signature Predicts Response to Decitabine Treatment in Elderly Patients with AML
Authors: Chenchen Zhao, Bei Jia, Liru Wang, David F. Claxton, W. Christopher Ehmann, Witold B. Rybka, Shin Mineishi, Seema Naik, Natthapol Songdej, Muhammad Khawaja, Raymond J. Hohl, Hong Zheng
Journal: Blood (2018)
Comparison of Hospital Costs and in-Hospital Outcomes of Patients Admitted with Sepsis with and without Non Hodgkin Lymphoma
Authors: Karan Jatwani, Shraddha Jatwani, Karan Chugh, Sridevi Rajeeve, Rakesh Kumar Sharma, Stuthi Perimbeti, Vivek Suresh Modi, Siva Krishna Mannem
Journal: Blood (2018)
Incidence, Clinical Characteristics, and Prognostic Significance Of Chromosome 3q Abnormalities In Patients With CML Blast Phase
Authors: Tapan M. Kadia, Naval Daver, Fiona Virani, Elias Jabbour, Sherry Pierce, Naveen Pemmaraju, Alfonso Quintas-Cardama, Gautam Borthakur, Susan O'Brien, Hagop M. Kantarjian, Jorge E. Cortes
Journal: Blood (2013)