tbuckley/cabot-search huggingface dataset:
Abstract 17897: Pharmacological Inhibition of PTEN Increases Myocardial Salvage, Reduces Infarct Size, and Decreases Adverse Post-infarction Left Ventricular Remodeling in a Porcine Model of Reperfused Myocardial Infarction
Authors: Carlos G Santos-Gallego, Belén Picatoste, Ida U Njerve, Torsten P Vahl, Kiyotake Ishikawa, Javier Sanz, Roger J Hajjar, Valentin Fuster, Juan Badimon
Journal: Circulation (2014)

RISK pathway is the main cardioprotective pathway against ischemia-reperfusion (I-R) injury, and it starts with the phosphorylation (activation) of Akt. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a primary phosphatase that negatively regulates Akt phosphorylation. We hypothesized that the PTEN inhibitor, VO-OHpic, increases myocardial salvage, reduces myocardial infarction (MI) size, and mitigates left ventricular (LV) remodeling in a porcine model of I-R. Methods: Acute MI was induced in 10 pigs by balloon occlusion of the proximal LAD for 60 min, followed by reperfusion. Animals randomly received VO-OHpic 15 minutes prior to reperfusion, or saline for controls. Animals were evaluated with cardiac MRI and 3D-echo at 1 week and 1 month post MI. Histology was performed after 1 month to assess LV remodeling. Results: One week after MI, despite similar of myocardium at risk in both groups (40.9 ± 2.5% vs 40.9 ± 2.5%, p=NS), VO-OHpic significantly reduced MI size (28.3 ±1.7% vs 36.7 ± ...
Abstract 19675: Testing Strategies and Poor Outcomes of Syncope among Medicare Beneficiaries
Authors: Meena P Rao, Lisa A McCoy, Judith Stafford, Lesley H Curtis, Sana Al-Khatib, Adrian F Hernandez
Journal: Circulation (2014)

Background: Syncope is a common problem among older patients in the United States and national guidelines recommend a variety of tests to determine the etiology. However, few data are available regarding how tests are used nationwide and outcomes of patients presenting with syncope. Methods: Using the nationally representative 5% sample of Medicare beneficiaries 65 years or older, we identified patients who had at least 1 inpatient or 2 outpatient claims for syncope between 2001 and 2010. We excluded beneficiaries with a pacemaker or implantable cardioverter defibrillator in situ prior to the incident syncope encounter that required no prior claim of syncope in the prior 365 days. Results: The overall incidence of syncope in 2001 was 11.8 per 1000 person years and remained stable over time ranging from 10.3 to 14.6 per 1000 person years. The average age of beneficiaries with syncope was 79, with the majority being women (63.3%) and white (87.5%). Hypertension was the most common comorbid condition (84%) followed by coronary heart disease (46.5%). When considering the tests ordered within 90 days of the incident encounter, the most frequently ordered tests were CT head (57%) and echocardiogram (50%). Holter monitors were ordered for 18% of beneficiaries, implantable loop recorders for 0.2%, tilt table testing for 4% and electrophysiology study for 2.7% of beneficiaries. From 2001 to 2010, the frequency of these tests did not significantly vary. Mortality at one year was 13% overall (17% for inpatients and 6% for outpatients). All cause readmission at one year was 44% with readmissions for syncope 9% (figure). Conclusion: Syncope is a common condition and is associated with a high mortality and hospitalization within 1 year of initial presentation. Guideline recommended diagnostic tests are ordered infrequently and represent an opportunity to improve care by developing a structured approach for the evaluation of syncope.
The prechemoradiotherapy/nadir ratio of white blood-cell count to predict tumor response and survival in locally advanced rectal cancer.
Authors: Joo Hwan Lee, Sung Hwan Kim, Jong Hoon Lee, Soo Yoon Sung, Hong Seok Jang
Journal: Journal of Clinical Oncology (2018)

783 Background: Predicting treatment response of preoperative chemoradiotherapy (CRT) in patients with rectal cancer is important for physicians to guide a patient to the relevant treatment. We evaluate the change of white blood cell (WBC) count before and during CRT if it is associated with susceptibility to the CRT and affects tumor response. Methods: Medical records of 641 patients with rectal cancer who received preoperative CRT followed by curative surgery were retrospectively reviewed. Complete blood cell counts were measured weekly before and during the radiation therapy. We assessed the pre-CRT/nadir ratio of WBC count for the treatment response to CRT and recurrence-free survival. Results: The enrolled patients were divided into two groups of high WBC ratio (HWR) and low WBC ratio (LWR) with the cutoff value of 0.49, which was found by receiver operating characteristic curve (Sensitivity, 0.38 and 1-Specificity, 0.22; p=0.007). In 641 patients, 490 (76.4%) were HWR group and 151 (23.6%) were LWR group. Complete pathologic response rates were 12.2% in HWR group and 23.8% in LWR group, respectively (p=0.001). Downstaging rates of each group were 37.8% and 48.3%, respectively (p=0.02). In the logistic regression analysis, CEA level over 5ng/ml (Adjusted OR 0.566, 95% CI 0.351-0.912; p=0.019) and HWR (Adjusted OR 0.412, 95% CI 0.256-0.663; p=0.001) were significant adverse factors of the pathologic complete response. The 5-year recurrence-free survival rate was significantly higher in LWR group than in HWR group (67.6% and 83.3%; p=0.001). Conclusions: Low WBC ratio predicts a good tumor response to the preoperative CRT, and is significantly associated with an improved recurrence-free survival in rectal cancer.
The impact of value-based payment on the referral of oncology patients to tobacco cessation services.
Authors: Louise Bedard, Jennifer J. Griggs
Journal: Journal of Clinical Oncology (2018)

116 Background: The purpose of this study is to investigate the relationship between the introduction of value-based payment, the initiation of a quality improvement project, and practices’ performance to refer or administer tobacco cessation counseling to patients. Methods: The Michigan Oncology Quality Consortium (MOQC) is a statewide quality collaborative sponsored by Blue Cross/Blue Shield of Michigan (BCBSM). MOQC uses ASCO's Quality Oncology Practice Initiative (QOPI) for measurement.Value-based payment (VBP) was introduced in 2017 by BCBSM. The VBP is achieved if a region reaches a target established for four QOPI measures. One of the four quality measures is QOPI's core measure 22bb: tobacco cessation counseling administered or patient referred. At the time the VBP was introduced, a subset of MOQC practices chose to initiate a quality project to improve performance on this measure. Analyses describes the performance of all MOQC practices with the introduction of the VBP, and performance of the practices who chose to revise their tobacco cessation processes to address performance. Results: The proportion of patients who were administered or referred to tobacco cessation services in participating MOQC practices was 49% (n = 793 charts) from abstracted rounds Spring 2014 - 2017. After the introduction of VBP, this proportion increased to 58% (n = 307 charts) in Fall 2017. Performance improved on this QOPI measure for both subsets of MOQC practices - those practices that chose to initiate a quality project focused on this measure (n = 19) and practices that selected another measure (n = 27). Practices that developed a quality project improved their aggregate proportion from 46% (Spring 2014-2017, n = 839 charts) to 51% (Fall 2017, n = 266 charts). Practices that focused on another quality measure improved from 51% (Spring 2014-2017, n = 789 charts) to 65% (Fall 2017, n = 265 charts). Conclusions: Our data suggest that the presence of VBP may have had a positive impact on referral patterns for tobacco cessation services for cancer patients. Additional analyses are required to determine if there is a combination or sequencing of VBP and process improvement strategies to optimize the delivery of quality care.
Quality assessment of tumor boards across an academic and community cancer network.
Authors: Daniel Aaron Roberts, Robert Stuver, Igor Schillevoort, Jessica A. Zerillo
Journal: Journal of Clinical Oncology (2018)

122 Background: Cancer tumor boards (TB), or multidisciplinary team meetings are standard of care in oncology care worldwide. Specific components are described by the American College of Surgeon's Commission on Cancer Program. Most data show consistent improvement in outcomes including a change in diagnostic findings, treatment, and possibly improved survival with TBs. Methods: We adapted a performance assessment tool based on a validated survey implemented in the United Kingdom. An initial survey aimed at assessing tumor board structure and design was sent to 21 TB leaders, and subsequently a tumor board quality assessment survey was sent to 175 participants throughout an academic and community network. The quality assessment survey required participants to identify an answer on a 5-point Likert scale in the categories of "very poor, poor, average, good, and very good". Results: TB leaders representing 16 of 21 (response rate 76%) TBs responded to the structure/design survey. Twelve TBs were from the academic center and included diseases such as Gynecologic Oncology, Cutaneous Oncology, Genitourinary Oncology, and Sarcoma, while four were from community sites. TB leaders indicated that 55% of TBs did not receive CME credit and 60% did not document their recommendations. One hundred eleven TB participants of 175 (response rate 63%) responded to the quality assessment survey. Participants identified the following strengths: 1) all relevant subspecialties present for meetings, 2) respectful teamwork and culture, and 3) operating on an organized agenda. Areas for improvement included: 1) inconsistent tumor board recommendation documentation and 2) post-meeting coordination of care. Results were reviewed with network and cancer center leadership as well as with the Cancer Committee. Conclusions: We assessed our own tumor boards across our cancer network by utilizing an adapted version of a validated TB performance measurement tool for the first time in the United States. Through this assessment we identified key areas for improvement including the need for obtaining CME credit for TB attendance, and developed a policy, process, and template for documenting TB recommendations in an easily accessible centralized location.
Methylation-dependent Tissue Factor Suppression Contributes to the Reduced Malignancy of IDH1-mutant Gliomas
Authors: Dusten Unruh, Snezana Mirkov, Brian Wray, Michael Drumm, Jonathan Lamano, Yuping D. Li, Qazi F. Haider, Rodrigo Javier, Kathleen McCortney, Amanda Saratsis, Denise M. Scholtens, Jann N. Sarkaria, C. David James, Craig Horbinski
Journal: Clinical Cancer Research (2018)

Gliomas with isocitrate dehydrogenase 1 mutations (IDH1mut) are less aggressive than IDH1 wild-type (IDH1wt) gliomas and have global genomic hypermethylation. Yet it is unclear how specific hypermethylation events contribute to the IDH1mut phenotype. Previously, we showed that the gene encoding the procoagulant tissue factor (TF), F3, is among the most hypermethylated and downregulated genes in IDH1mut gliomas, correlating with greatly reduced thrombosis in patients with IDH1mut glioma. Because TF also increases the aggressiveness of many cancers, the current study explored the contribution of TF suppression to the reduced malignancy of IDH1mut gliomas.Experimental Design: TF expression was manipulated in patient-derived IDH1mut and IDH1wt glioma cells, followed by evaluation of in vitro and in vivo behavior and analyses of cell signaling pathways.A demethylating agent, decitabine, increased F3 transcription and TF-dependent coagulative activity in IDH1mut cells, but not in IDH1wt cells. TF induction enhanced the proliferation, invasion, and colony formation of IDH1mut cells, and increased the intracranial engraftment of IDH1mut GBM164 from 0% to 100% (P = 0.0001). Conversely, TF knockdown doubled the median survival of mice engrafted with IDH1wt/EGFRvIIIamp GBM6, and caused complete regression of IDH1wt/EGFRamp GBM12 (P = 0.001). In vitro and in vivo effects were linked to activation of receptor tyrosine kinases (RTK) by TF through a Src-dependent intracellular pathway, even when extracellular RTK stimulation was blocked. TF stimulated invasion predominately through upregulation of β-catenin.These data show that TF suppression is a component of IDH1mut glioma behavior, and that it may therefore be an attractive target against IDH1wt gliomas.
Identification of a 3′‐Untranslated Genetic Variant of <i><scp>RARB</scp></i> Associated With Carotid Intima‐Media Thickness in Rheumatoid Arthritis: A Genome‐Wide Association Study
Authors: Raquel López‐Mejías, F. David Carmona, Fernanda Genre, Sara Remuzgo‐Martínez, Carlos González‐Juanatey, Alfonso Corrales, Esther F. Vicente, Verónica Pulito‐Cueto, José A. Miranda‐Filloy, Marco A. Ramírez Huaranga, Ricardo Blanco, Montserrat Robustillo‐Villarino, Javier Rodríguez‐Carrio, Mercedes Alperi‐López, Juan J. Alegre‐Sancho, Verónica Mijares, Leticia Lera‐Gómez, Eva Pérez‐Pampín, Antonio González, Rafaela Ortega‐Castro, Chary López‐Pedrera, Mari L. García Vivar, Catalina Gómez‐Arango, Enrique Raya, Javier Narvaez, Alejandro Balsa, Francisco J. López‐Longo, Patricia Carreira, Isidoro González‐Álvaro, Luis Rodríguez‐Rodríguez, Benjamín Fernández‐Gutiérrez, Iván Ferraz‐Amaro, Oreste Gualillo, Santos Castañeda, Javier Martín, Javier Llorca, Miguel A. González‐Gay
Journal: Arthritis & Rheumatology (2018)

To investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA).We performed a genome-wide association study (GWAS) in which, after quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analyzed in 2,989 RA patients of European origin. Data on subclinical atherosclerosis, obtained through assessment of carotid intima-media thickness (CIMT) and presence/absence of carotid plaques by carotid ultrasonography, were available for 1,355 individuals.A genetic variant of the RARB gene (rs116199914) was associated with CIMT values at the genome-wide level of significance (minor allele [G] β coefficient 0.142, P = 1.86 × 10-8 ). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biologic pathway enrichment and predictive protein-protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (Gene Ontology no. 0032964; false discovery rate-adjusted P = 4.01 × 10-3 ). Furthermore, our data suggest potential influences of the previously described candidate CV risk loci NFKB1, MSRA, and ZC3HC1 (P = 8.12 × 10-4 , P = 5.94 × 10-4 , and P = 2.46 × 10-4 , respectively).The present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA.
A systematic review of clinical trial registration in major respiratory journals 2010–2018
Authors: Nelli S.M. Suntila, Alexandria Smith, Yusuf Al-Dabbagh, James D. Chalmers
Journal: European Respiratory Journal (2018)

The results of randomised clinical trials are regarded as the highest level of evidence for informing clinical guidelines and clinical practice [1, 2]. The robustness of conduct and reporting of the results of randomised clinical trials is therefore of primary importance. To improve the transparency and quality of reporting of clinical trials, the International Committee of Medical Journal Editors (ICMJE) endorsed a policy on mandatory registration of clinical trials, which came into effect in July 2005 [3]. The trial registration recommendations outlined by the ICMJE state that a trial must be registered in a publicly accessible registry, before the enrolment of the first study participants, in order to be considered for publication. This policy is designed to reduce publication bias, prevent selective reporting of desirable or non-reporting of undesirable results, and reduce research waste by making the research community aware of what questions are already being addressed by active trials. Retrospective trial registration remains common in respiratory clinical trials, and may be associated with reporting bias <http://ow.ly/S7p230m5kqV>
Sixty seconds on . . . P-hacking
Authors: Nigel Hawkes
Journal: BMJ (2018)

It’s proved so for Brian Wansink, a prominent food researcher who has resigned from his post at Cornell University after six papers were retracted by JAMA and its specialty journals over suspicions of P-hacking.1

Playing around with data until you find a correlation that meets the statistical standard for significance, which is P less than 0.05.

P measures …
Update on functional recovery process for the injured athlete: return to sport continuum redefined
Authors: Matthew Buckthorpe, Antonio Frizziero, Giulio Sergio Roi
Journal: British Journal of Sports Medicine (2018)

The traditional functional recovery model and return to sport (RTS) decision-making process after long-term injury is insufficient in the real world of sports medicine. There are lower than ideal numbers of athletes returning to competitions after certain injury types.1 2 Additionally, those who do RTS have heightened risk of reinjury,3 may not return to preinjury performance levels,4 or may be unable to sustain the same level of competitive play in the subsequent years after injury.5 This paper provides an update on the RTS process, reflecting the new literature and knowledge in the area as well as applied practice, to support practitioners working with athletes after injuries and in particular after severe injuries (>28 days).6 

A dichotomous conception of functional recovery was common in the past (and often still present) which involved the separation of clinical rehabilitation and RTS. Initially, the patient begins with the medical team before been transferred to the performance team (coaching and fitness staff) for sport-specific training and RTS. There is often little or no overlap in the process, and limited communication and sharing of knowledge during the functional recovery process.

When there is a need to prepare the athlete for direct re-entry into sport after injury, it is necessary to consider an overlap of the rehabilitation and RTS processes. This area of overlap …
Deconditioning after "Moving On" rehabilitation.
Authors: Suzanne R. Fanning
Journal: Journal of Clinical Oncology (2018)

291 Background: “Moving On” is a 12-week physical rehabilitation program that is offered to patients following cancer treatment. Autologous hematopoietic stem cell transplantation (HSCT) is considered a more aggressive cancer treatment due to myeloablative doses of chemotherapy. Our previous research has shown that deconditioning at the time of referral to Moving On is not significantly different in HSCT patients and non-HSCT cancer patients. Our objective here is to determine how deconditioning after Moving On completion compares in HSCT and non-HSCT groups, as well as by age. Methods: We retrospectively reviewed data from Moving On referrals made between March 2013 and March 2016 (N = 1,057) who completed the Moving On program (N = 322). This includes patients with solid or hematologic malignancies, some of whom received HSCT. Brief Fatigue Inventory scores and 6-minute timed walk (6-MTW) distances were recorded to assess deconditioning. Results: We found 296 of 615 (48%) non-HSCT patients evaluated for Moving On, completed the program; 26 of 43 (60%) HSCT patients evaluated for Moving On completed the program. For those completing Moving On, we found a mean fatigue score of 1.6 in non-HSCT patients (SD = 1.9) and 1.3 in HSCT patients (SD = 2.3) (p = 0.43). The mean distance walked in six minutes was 1543 feet (SD = 237) in non-HSCT patients and 1624 feet (SD = 247) in HSCT patients (p = 0.11). In patients &lt; 70 years old, average fatigue scores were 1.6 for non-HSCT and 1.2 in HSCT (p = 0.29); average 6-MTW distances were 1564 ft. for non-HSCT and 1644 ft. in HSCT (p = 0.17). In patients ≥70 years old, average fatigue scores were 1.4 for non-HSCT and 1.6 in HSCT (p = 0.82); average 6-MTW distances were 1451 feet for non-HSCT and 1560 feet in HSCT (p = 0.20). Conclusions: We find that 25% more HSCT patients complete Moving On than non-HSCT patients. There is no significant difference in post-Moving On fatigue scores or 6-MTW distances between HSCT and non-HSCT groups. A significant difference in 6-MTW by age, is found in the non-HSCT group but not in HSCT patients. This may be due to selection bias in this group, as more fit patients ≥70 undergo HSCT. Our results show that deconditioning following rehabilitation in autologous HSCT is comparable to cancer patients not receiving HSCT, regardless of age.
Abstract 12199: Prognostic Value of Cardiac Time Intervals Measured by Tissue Doppler Imaging M-Mode in the General Population
Authors: Tor Biering-Sørensen, Rasmus Mogelvang, Jan Skov Jensen
Journal: Circulation (2014)

Purpose: Tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy, fast, and precise method to estimate the cardiac time intervals from one cardiac cycle (Figure). The aim was to evaluate the usability of the cardiac time intervals in predicting major cardiovascular events (MACE) in the general population. Methods: In a large community based population study, cardiac function was evaluated in 1,915 participants by both conventional echocardiography and by TDI. The cardiac time intervals, including the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI M-mode through the mitral leaflet (Figure). IVCT/ET, IVRT/ET and the myocardial performance index (MPI=(IVRT+IVCT)/ET) were calculated. Results: During follow-up (median 10.8 years), 383 (20%) participants reached the combined endpoint MACE (ischemic heart disease, heart failure or cardiac death). After multivariable adjustment for clinical predictors and conventional echocardiography, only the combined indexes, including information on both the systolic and diastolic performance (IVRT/ET and MPI), remained significant prognosticators (IVRT/ET: Subdistribution Hazard Ratio (SHR) 1.16 (1.00-1.34), p = 0.047; MPI: 1.11 (1.03-1.23), p = 0.024). Adding IVRT/ET or MPI to a model already including all other echocardiographic parameters resulted in a significant increase in the Harrell’s c-statistics (p&lt;0.05 for both). Finally, when adding IVRT/ET or MPI to the clinical predictors improved reclassification significantly (p&lt;0.05 for both). Conclusion: In the general population, the combined cardiac time intervals which include information on both the systolic and diastolic function in one index (IVRT/ET and MPI) are not only powerful and independent predictors of future MACE, but provide additional prognostic information to clinical and conventional echocardiographic measures of systolic and diastolic function.