tbuckley/cabot-search huggingface dataset:
Metrics to evaluate the performance of cancer center leadership.
Authors: Michael T. Halpern, Hamlet Gasoyan, William E. Aaronson
Journal: Journal of Clinical Oncology (2019)

10 Background: Cancer centers are diverse health care organizations that involve clinicians and researchers focused on understanding, treating, and controlling cancer in the populations they serve. While there are many metrics used to evaluate cancer center performance, few standardized measures have been identified to evaluate the performance of cancer center leadership. The goal of this manuscript is to systematically identify, compare, and categorize metrics used to evaluate the leadership of U.S. cancer centers. Methods: We performed a structured, systematic electronic search of peer-reviewed journals using Medline to identify English language articles discussing metrics used to evaluate cancer center leadership. Identified studies were reviewed by two independent reviewers to determine appropriateness for inclusion. Metrics were classified using ten a priori-defined categories of evaluation for data abstraction. Results: We included 34 manuscripts in this review. The most commonly-discussed evaluation metric category is organizational strategy/planning (31 of the 34 papers), followed by leader characteristics (25 papers), clinical performance (21), and facility characteristics (20). Organizational strategy/planning include governance structure; strategic development; quality assurance/improvement; mission/vision; business planning; and program development. Leader characteristic metrics include communication; vision/strategic thinking; personal skills; team coordination; leadership style; and staff development. Clinical Performance metrics focus on delivery of and outcomes from clinical services while facility characteristics include space allocation and access to support services. Conclusions: The metrics reviewed and synthesized in this report may be considered measurable outcomes to evaluate whether cancer center leadership demonstrates key competencies. Additional research is needed to explore the link between metrics used to evaluate cancer center leaders, the desired competencies for healthcare leaders, and objective measures of whether a cancer center is “successful”.
Effect of a Nutritional and Behavioral Intervention on Energy-Reduced Mediterranean Diet Adherence Among Patients With Metabolic Syndrome
Authors: Carmen Sayón-Orea, Cristina Razquin, Mónica Bulló, Dolores Corella, Montserrat Fitó, Dora Romaguera, Jesús Vioque, Ángel M. Alonso-Gómez, Julia Wärnberg, J. Alfredo Martínez, Luís Serra-Majem, Ramón Estruch, Francisco J. Tinahones, José Lapetra, Xavier Pintó, Josep A. Tur, José López-Miranda, Aurora Bueno-Cavanillas, Miguel Delgado-Rodríguez, Pilar Matía-Martín, Lidia Daimiel, Vicente Martín Sánchez, Josep Vidal, Clotilde Vázquez, Emilio Ros, Miguel Ruiz-Canela, José V. Sorlí, Olga Castañer, Miquel Fiol, Eva M. Navarrete-Muñoz, Fernando Arós, Enrique Gómez-Gracia, M. Angeles Zulet, Almudena Sánchez-Villegas, Rosa Casas, Rosa Bernal-López, José M. Santos-Lozano, Emili Corbella, Cristina Bouzas, Ana García-Arellano, Josep Basora, Eva M. Asensio, Helmut Schröder, Manuel Moñino, Manoli García de la Hera, Lucas Tojal-Sierra, Estefanía Toledo, Andrés Díaz-López, Albert Goday, Jordi Salas-Salvadó, Miguel A. Martínez-González
Journal: JAMA (2019)

High-quality dietary patterns may help prevent chronic disease, but limited data exist from randomized trials about the effects of nutritional and behavioral interventions on dietary changes.To assess the effect of a nutritional and physical activity education program on dietary quality.Preliminary exploratory interim analysis of an ongoing randomized trial. In 23 research centers in Spain, 6874 men and women aged 55 to 75 years with metabolic syndrome and no cardiovascular disease were enrolled in the trial between September 2013 and December 2016, with final data collection in March 2019.Participants were randomized to an intervention group that encouraged an energy-reduced Mediterranean diet, promoted physical activity, and provided behavioral support (n = 3406) or to a control group that encouraged an energy-unrestricted Mediterranean diet (n = 3468). All participants received allotments of extra-virgin olive oil (1 L/mo) and nuts (125 g/mo) for free.The primary outcome was 12-month change in adherence based on the energy-reduced Mediterranean diet (er-MedDiet) score (range, 0-17; higher scores indicate greater adherence; minimal clinically important difference, 1 point).Among 6874 randomized participants (mean [SD] age, 65.0 [4.9] years; 3406 [52%] men), 6583 (96%) completed the 12-month follow-up and were included in the main analysis. The mean (SD) er-MedDiet score was 8.5 (2.6) at baseline and 13.2 (2.7) at 12 months in the intervention group (increase, 4.7 [95% CI, 4.6-4.8]) and 8.6 (2.7) at baseline and 11.1 (2.8) at 12 months in the control group (increase, 2.5 [95% CI, 2.3-2.6]) (between-group difference, 2.2 [95% CI, 2.1-2.4]; P < .001).In this preliminary analysis of an ongoing trial, an intervention that encouraged an energy-reduced Mediterranean diet and physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significantly greater increase in diet adherence after 12 months. Further evaluation of long-term cardiovascular effects is needed.isrctn.com Identifier: ISRCTN89898870.
A Novel Cycs Missense Mutation in the α-Helix of the Cycs C-Terminal Domain Causes Non-Syndromic Thrombocytopenia
Authors: Yuri Uchiyama, Kunio Yanagisawa, Shinji Kunishima, Masaaki Shiina, Yoshiyuki Ogawa, Mitsuko Nakashima, Satoko Miyatake, Satomi Mitsuhashi, Atsushi Takata, Noriko Miyake, Kazuhiro Ogata, Hiroshi Handa, Naomichi Matsumoto, Takeshi Mizuguchi
Journal: Blood (2018)
The Clinical Utility of Pharmacogenomics Testing in Assessing Tyrosine Kinase Inhibitor Therapy, Intolerance and Responses in Patients with Chronic Myelogenous Leukemia
Authors: Darci Zblewski, Naseema Gangat, Michelle A. Elliott, Aref Al-Kali, Mark R. Litzow, C. Christopher Hook, Tyler Mielke, Alexandra Wolanskyj, Willam Hogan, Animesh Pardanani, Mithun Vinod Shah, Hassan B. Alkhateeb, Lindsey Ann Kluck, Adrienne Nedved, Kristen McCullough, Matthew Smith, Tammy McAllister, Konstantinos Lazaridis, A Keith Stewart, Mrinal M. Patnaik
Journal: Blood (2018)
Tumor Associated Antigen Reactive Donor T Cells As Elementary Components of Streptamer Isolated Multi-Antigen Specific T Cells
Authors: Marthe C.J. Roex, Ellis van Liempt, Lois Hageman, Lothar Germeroth, Constantijn J.M. Halkes, J.H. Frederik Falkenburg, Inge Jedema
Journal: Blood (2014)
Treatment patterns and cost of care in commercially insured relapsed acute myeloid leukemia (AML) patients in the outpatient setting.
Authors: Chunlin Qian, Feng Lin, Jackie Kwong
Journal: Journal of Clinical Oncology (2019)

99 Background: Outpatient administration of cancer therapy has become more common in recent years. The objective of this study was to evaluate treatment patterns and cost of care for relapsed AML patients in the outpatient setting. Methods: A retrospective analysis was performed using the IQVIA Health Plan Claims Data–US database. Patients were eligible if they had at least one outpatient claim associated with relapsed AML diagnosis as identified by ICD-9 (205.02) and ICD-10 (C92.02, C92.42, C92.52, C92.62, C92.A2) codes between 1/1/2009 to 12/31/2017, had no inpatient claim for AML diagnosis within 30 days of index claim, and received treatment for relapsed AML as recommended by NCCN guidelines within 30 days of index outpatient claim. Utilization of high intensity chemotherapy (HIC), hypomethylating agent (HMA), low-dose cytarabine (LoDAC) and sorafenib, duration of treatment and the cost per 28-day treatment cycle were examined. Patients were censored at either treatment switching or end of follow-up. Results: Of the 6,242 patients with relapsed AML diagnosis in the IQVIA™ database, 709 did not have inpatient claim of which only 281 patients [26.0% &gt;65 years; 43.8% females] met inclusion criteria and received a total of 1,336 treatment cycles of NCCN recommended treatment as outpatient. About 75% of patients (n=209) received HMA, 6% (n=17) received HIC and 19.6% (n=55) received LoDAC. Patients &gt;65 years were more likely to receive HMA than HIC and LoDAC (p=0.003). Mean (SD) number of treatment cycles for HMA, high-intensity chemotherapy and LoDAC was 5.7 (5.2), 1.2 (0.4) and 2.2 (1.4), respectively. Sorafenib was used in 4.8%, 17.6% and 3.6% patients treated with HMA, HIC and LoDAC. Mean (SD) cost per cycle was $11,246 (8,895), $10,620 (16,722), $3,254 (2,948), and $10,799 (3,057) for HMA, HIC, LoDAC and sorafenib, respectively. Conclusions: Treatment for relapsed AML in the outpatient setting without hospitalization was uncommon during the study period. Low-intensity regimens remain the mainstay of therapy in the outpatient setting, suggesting that treatment toxicities and monitoring requirement are key determinants for treatment setting for relapsed AML.
Long-Term Follow-Up of Patients With Nodular Lymphocyte-Predominant Hodgkin Lymphoma Treated in the HD7 to HD15 Trials: A Report From the German Hodgkin Study Group
Authors: Dennis A. Eichenauer, Annette Plütschow, Michael Fuchs, Stephanie Sasse, Christian Baues, Boris Böll, Bastian von Tresckow, Volker Diehl, Peter Borchmann, Andreas Engert
Journal: Journal of Clinical Oncology (2019)

PURPOSE The optimal treatment of newly diagnosed nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is ill defined. We therefore conducted a retrospective analysis using the database of the German Hodgkin Study Group (GHSG). PATIENTS AND METHODS The long-term course of 471 patients with NLPHL (early stages, n = 251; intermediate stages, n = 76; advanced stages, n = 144) who had received stage-adapted first-line treatment in the randomized GHSG HD7 to HD15 studies was investigated. Treatment consisted of radiotherapy alone, chemotherapy alone, or combined-modality approaches. RESULTS The median age at NLPHL diagnosis was 39 years (range, 16 to 75 years). Patients were mostly male (75.8%). The median observation time was 9.2 years. At 10 years, progression-free survival and overall survival estimates were 75.5% and 92.1% (early stages, 79.7% and 93.3%; intermediate stages, 72.1% and 96.2%; advanced stages, 69.8% and 87.4%), respectively. A total of 48 patients (10.2%) developed a second malignancy during follow-up (non-Hodgkin lymphoma, n = 13; leukemia, n = 6; solid tumor, n = 25; unspecified malignancy, n = 4). Death occurred in 43 patients (9.1%). However, only a minority of deaths were NLPHL related (n = 10), whereas second malignancies (n = 20) and nonmalignant conditions possibly associated with radiotherapy or chemotherapy (n = 13) caused the death in the majority of patients. CONCLUSION The overall outcome of patients with NLPHL who had received Hodgkin lymphoma–directed first-line treatment in randomized GHSG trial protocols was good. Nonetheless, treatment optimization is still necessary to reduce toxicity in standard-risk patients and to improve the prognosis in high-risk patients.
Abstract 226: Apoai Mimetic Peptide 6f Prevent Pulmonary Hypertension Induced by Oxidized Lipids
Authors: Gregoire Ruffenach, Ellen O'Connor, Mylene Vaillancourt, Shervin Sarji, Nancy Cao, Laila Aryan, Christine Cunningham, Victor Grijalva, Soban Umar, Srininivasa Reddy, Mansoureh Eghbali, Donya Moazeni
Journal: Circulation Research (2019)

Introduction: Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial occlusion leading to increased pulmonary arterial pressure. Recently, a growing body of evidence demonstrated a robust increase in oxidized lipids, including 15-hydroxyeicosatetraenoic acids (15HETE), in the lungs and plasma of PAH patients and animal models of pulmonary hypertension (PH). Nonetheless, the the causal role of 15HETE in promoting PH development remains elusive. In order to investigate this mechanism, we fed wild type mice with a diet rich in 15HETE and examine whether ApoA-I mimetic peptide can rescue PH induced by 15HETE. Methods: Wild type male mice (C57BL/6) were fed for 3 weeks with regular chow (n=16-21 mice/group), 15HETE (5μg/day), 15HETE diet supplemented with either empty vector or 6F for the last week of 15HETE diet. PH development was assessed every week via serial echocardiography. Right ventricular systolic pressure (RVSP) was measured via heart catheterization. RV hypertrophy index (RV/[IVS+LV]) was measured. Lung morphology and lipid accumulation were assessed using H&amp;E and Oil red O staining. Results: Echocardiography revealed the first sign of PH as early as one week after starting 15HETE diet and a significant decrease in the pulmonary arterial acceleration time (PAAT) after 2 weeks of treatment (16.6±1.9 vs. 20.6±1.4 msec, p&lt;0.05). At the end of three weeks, mice on 15HETE diet had significantly higher RVSP (31.3±1.1 vs. 38.4±2.3 mmHg, p&lt;0.05) and RV hypertrophy index (0.26 ± 0.02 vs. 0.33 ±0.02, p&lt;0.05). This increased pressure was concomitant with a significant increase in pulmonary arteriolar thickness in mice on 15-HETE diet compared to regular diet (35.1±0.8 vs 53.4±1, p&lt;0.05). At the end of three weeks mice treated with 6F showed a PAAT similar to control value(19±0.5 msec) concomitant with a significantly lower RVSP than mice fed with 15HETE+empty vector (33.6 ±5.7 vs 40.3±4.6, p&lt;0.05). Conclusion: Our data demonstrates that APOA-I mimetic peptide 6F is able to rescue pre-exisiting PH induced by 15-HETE diet in wild type mice.
Genetically determined serum urate levels and cardiovascular and other diseases in UK Biobank cohort: A phenome-wide mendelian randomization study
Authors: Xue Li, Xiangrui Meng, Yazhou He, Athina Spiliopoulou, Maria Timofeeva, Wei-Qi Wei, Aliya Gifford, Tian Yang, Tim Varley, Ioanna Tzoulaki, Peter Joshi, Joshua C. Denny, Paul Mckeigue, Harry Campbell, Evropi Theodoratou
Journal: PLoS Medicine (2019)

Background The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. Methods and findings A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40–69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10−4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization. Conclusion In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities.
Abstract 454: Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology
Authors: Rafael Jaimes, Damon McCullough, Bryan Siegel, Luther Swift, Daniel McInerney, James Hiebert, Jiansong Sheng, Nikki G Posnack
Journal: Circulation Research (2019)

Background: Phthalates are employed as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients. Methods and Results: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations following an exchange transfusion procedure. 30-min exposure to MEHP increased the atrioventricular node (147 vs. 107msec) and ventricular (117 vs. 77.5msec) effective refractory periods, compared with controls. Optical mapping revealed prolonged action potential duration (APD) at slower pacing cycle lengths, akin to reverse use-dependence. The plateau phase of the APD restitution curve steepened and became monophasic in MEHP-exposed hearts (0.18 vs. 0.06 slope). APD lengthening occurred during late-phase repolarization resulting in triangulation (70.3 vs. 56.6 msec). MEHP-exposure also slowed epicardial conduction velocity (35 vs. 60 cm/sec), which may be partly explained by inhibition of Na v 1.5 (874 μM and 231 μM IC50, fast and late sodium current). Conclusions: This study highlights the impact of acute MEHP exposure, using a clinically-relevant dose, on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications – given that action potential triangulation and electrical restitution modifications are a risk factor for early after depolarizations and cardiac arrhythmias.
Diabetes mellitus in ankylosing spondylitis
Authors: Young Ho Lee, Gwan Gyu Song
Journal: Annals of the Rheumatic Diseases (2019)

Diabetes mellitus in ankylosing spondylitisWe read with interest the article by Liao et al 1 regarding diabetes mellitus in ankylosing spondylitis and the meta-analysis by Mathieu et al.This nationwide cohort study demonstrated that the overall incidence of diabetes mellitus was 1.21-fold higher in the ankylosing spondylitis group than in the non-ankylosing spondylitis group, 1 and Mathieu et al's research showed an increased cardiovascular events in ankylosing spondylitis. 2The results of Liao et al are in concordance with those of a previous cohort study by Chen et al which showed that the incidence of diabetes mellitus was 1.17-fold higher in the ankylosing spondylitis cohort than in the non-ankylosing spondylitis cohort, with an adjusted HR of 1.16. 3 However, some methodological issues must be discussed.First, the definition of the control group used in this cohort study is too broad.What does the non-ankylosing spondylitis group mean?Second, the statistical robustness of cohort studies is lower than that of randomised trials because of potential biases related to adjustments for confounding variables.Many unhealthy lifestyle habits, including unhealthy dietary patterns, decreased physical activity, sedentary lifestyle and smoking, have been found to be associated with an increased risk of diabetes mellitus. 4In addition, patients with hypertension are more likely to have diabetes mellitus through increased insulin resistance. 5To reduce the effect of potential confounding in observational studies, it would be appropriate to analyse data that is adjusted to account for confounding factors.Third, observational studies are prone to bias, such as reverse causation and residual confounding, thereby precluding a clear understanding of the association between ankylosing spondylitis and diabetes mellitus.Although the investigation of the mechanism underlying the association between ankylosing spondylitis and diabetes mellitus is beyond the scope of this study, further study using Mendelian randomisation, a technique that uses genetic variants as instrumental variables, is needed to assess whether an observational association between a risk factor and an outcome is consistent with a causal effect.
The Survivin Suppressant YM155 Overcomes Microenvironment-Mediated Immune Resistance In a Humanized Multiple Myeloma Mouse Model
Authors: Sanne J. de Haart, Monique C. Minnema, Julie H. Huang, Tineke Aarts-Riemens, Henk Lokhorst, Anton Martens, Constantine S. Mitsiades, Tuna Mutis
Journal: Blood (2013)
Abstract 239: Selective Right-sided Electrical Remodeling In A Pure Model Of Pulmonary Hypertension Promotes Micro-reentrant Arrhythmias
Authors: Benjamin Strauss, Emerson Obus, Nestor Bedoya, Yassine Sassi, Fadi G Akar
Journal: Circulation Research (2019)

Background: Pulmonary arterial hypertension (PAH) is characterized by elevated mean PA pressures that increase right ventricular (RV) afterload, leading to RV failure. Whereas structural and mechanical decompensation in PAH are well established, the extent of electrophysiological (EP) remodeling and arrhythmia propensity are far less clear. This is, in large part, because PAH-related EP properties have been exclusively studied in the monocrotaline (MCT) model, which is confounded by major extra-pulmonary toxicities, including liver failure and direct myocardial damage. To address this knowledge gap, we performed a comprehensive evaluation of the EP substrate, including arrhythmia dynamics, in a new pure model of PAH. Methods: Sprague Dawley rats underwent surgical left pneumonectomy followed by injection of the VEGF inhibitor Sugen 5416 (S/P), or underwent no intervention (CTRL). 5 wks later, rats were euthanized for high-resolution optical action potential (AP) mapping studies in ex vivo perfused hearts. Results: 6/6 S/P vs 0/5 CTRL hearts were prone to pacing-induced VT (P&lt;.05). Underlying this differential susceptibility was disproportionate RV sided prolongation of AP duration in S/P. This, in turn, promoted the formation of right-sided AP alternans at physiological rates in S/P but not CTRL. Correspondingly, KCND2 mRNA transcripts were downregulated by 80X in the RV of S/P relative to CTRL. While propagation was impaired at all rates in S/P, the most profound decrease in conduction velocity (53%) was always observed immediately prior to VT initiation. Nav1.5 and Cx43 mRNA expression were not altered in S/P. In contrast Col1a1, Col3a1, and fibronectin transcripts were upregulated implicating fibrosis in impaired conduction. The average wavelength was significantly decreased in S/P relative to CTRL (P&lt;.05). Once generated, VT was sustained by multiple microreentrant circuits likely facilitated by the short wavelengths. Conclusion: In this pure model of PAH, we document highly selective RV-sided EP remodeling that facilitates the initiation of multi-wavelet micro-reentry underlying VT. The S/P model represents a severe form of PAH that allows the study of EP properties without the confounding influence of extra-pulmonary toxicity.