tbuckley/cabot-search huggingface dataset:
Abstract 16240: Tristetraprolin (TTP) is a Novel Regulator of Branched-chain Amino Acid (BCAA) Catabolism in the Heart
Authors: Sumeyye Yar, Hsiang-Chun Chang, Meng Shang, Hossein Ardehali
Journal: Circulation (2015)

Introduction: Heart failure (HF) is associated with the accumulation of branched-chain amino acids (BCAAs) in heart and plasma. Besides, BCAAs are essential for normal cell growth and function. Therefore, tight regulation of BCAA metabolism is crucial to maintain normal cellular homeostasis. Tristetraprolin (TTP), an mRNA binding protein that promotes the degradation of its targets and regulates a number of biological processes including cellular metabolism. In in silico analyses, we identified the E2 subunit of branched-chain α-ketoacid dehydrogenase complex (BCKDC), the rate-limiting enzyme complex in BCAA catabolism, as a potential target of TTP. Here we assess the hypothesis that TTP plays a regulatory role in BCAA catabolism through regulating BCKDC-E2 in the heart. We also investigate TTP’s contribution in the pathogenesis of HF by modulating BCAA catabolism. Results: We observed a significant increase in TTP levels in cardiac tissue of human HF and mouse myocardial infarct induced HF samples. We also showed that deletion of TTP significantly decreases BCAA levels in vitro. As BCAA accumulation in the heart is associated with the pathogenesis of HF, we investigated whether TTP can regulate cardiac BCAA catabolism. Computational analysis of mRNAs of enzymes, which are involved in BCAA catabolism, revealed highly conserved TTP binding sites in BCKDC-E2 mRNA, suggesting that it is a potential target of TTP. BCKDC-E2 mRNA levels were significantly higher in the heart of TTP knock-out mice and TTP siRNA treated cardiomyocytes. Additionally, the mRNA stability of BCKDC-E2 was higher in cardiomyocytes with TTP downregulation, further confirming that TTP regulates the stability of this mRNA. Moreover, RNA co-immunoprecipitation studies demonstrated that TTP physically interacts with the BCKDC-E2 mRNA. Finally, we showed that BCKDC-E2 mRNA levels were significantly decreased in human HF samples. Conclusion: Our data indicate that TTP levels are increased in HF samples and TTP regulates BCAA catabolism in the heart by binding to and degrading BCKDC-E2 mRNA. These findings suggest that alterations in TTP expression may play a role in the development of HF based on its effect upon BCKDC-E2 and BCAA catabolism.
Black and Asian doctors earn less than their white colleagues, official NHS figures show
Authors: Abi Rimmer
Journal: BMJ (2018)

New figures showing that black and Asian doctors earn less on average than their white colleagues are evidence of “unacceptable discrimination” in NHS pay levels, the BMA has said.

Data from NHS Digital on mean basic pay show that black female doctors earn £801 (€900; $1042) a month less than their white counterparts, while Asian female doctors earn £344 a month less than white female doctors.1

White male doctors earn £791 more a month than their …
Institutional adherence to National Comprehensive Cancer Network (NCCN) guidelines in neoadjuvant treatment of breast cancer and its correlation to outcomes.
Authors: Raju Kumar Vaddepally, Amal Hejab, Haythem Y. Ali
Journal: Journal of Clinical Oncology (2018)

47 Background: The aim of the study is to assess the adherence to National Comprehensive Cancer Network (NCCN) guidelines in the neoadjuvant treatment of breast cancer and evaluate its correlation to outcomes. Higher adherence rates correlate with improved survival and are a potential measure of the quality of care. Methods: We screened patients who were treated with neoadjuvant chemotherapy at our institution for the years 2015 &amp; 2016, a total 46 patients met the criteria. To evaluate adherence we tabulated 8 adherence categories per NCCN. We then screened patients who were only eligible to receive the treatment specific to a certain adherence category. A total adherence rate was calculated by dividing the number of categories for which they underwent intervention by the total number of eligible adherence categories. Rates of pathologic complete response (PCR) and Breast Conservation surgery (BCS) were calculated to measure the outcomes. Results: We had 9 triple negative breast cancer (TNBC), 28 Her2 overexpression (Her2+) and 17 triple positive patients. We had 100% adherence in categories such as, appropriate pre-chemotherapy evaluation {total eligible patients, n = 46}, completeness of histopathology report (n = 46), use of anti-Her2 antibody drug in patients with Her2 overexpression positive by IHC or FISH (n = 28) and adjuvant radiation therapy (n = 39). In the following categories, adherence rates were as follows, 70% (n = 33) genetic consult, 69% (n = 32) reconstructive surgery, 65% (n = 46) cancer distress screen performed. We could not assess the adherence to reproductive gynecology consult. Our median total adherence rates were 85% for all of the adherence categories in eligible patients. We had PCR and BCS rates of 39% &amp; 41% respectively. Further analysis showed PCR &amp; BCS rates of 46% &amp; 39% in Her2+ patients, 33% &amp; 44% in TNBC patients, 35% &amp; 38% in Doxorubicin treatment and 46% &amp; 39% in anti-Her2 antibody treatment group respectively. Conclusions: Our study shows adherence to NCCN guidelines leads to improved outcomes. To improve quality of care, institutions should closely monitor the adherence to NCCN or other alternative national guidelines.
Abstract 10460: Completeness of Revascularization and its Impact on the Outcomes of a Staged Approach of Percutaneous Coronary Intervention Followed by Minimally Invasive Valve Surgery for Patients With Concomitant Coronary Artery and Valvular Heart Disease
Authors: Andres M Pineda, Ramesh Chandra, Saqib A Gowani, Christos G Mihos, Orlando Santana, Ajay J Kirtana, Gregg W Stone, Paul Kurlansky, Craig R Smith, Nirat Beohar
Journal: Circulation (2015)

Introduction: A staged approach of percutaneous coronary intervention (PCI) followed by minimally invasive valve surgery (MIVS) is an alternative to the conventional combined coronary artery bypass and valve surgery for patients with concomitant coronary artery and valve disease. Hypothesis: Incomplete revascularization may negatively affect clinical outcomes amongst patients with severe coronary artery and valve disease undergoing a staged approach of PCI followed by MIVS. Methods: A total of 138 patients, who underwent a staged approach between January 2009 and June 2013, were retrospectively evaluated. Coronary angiograms were reviewed by 2 cardiologists blinded to outcomes and were then categorized into 2 groups: complete or incomplete revascularization, which was defined as ≥1 major epicardial coronary arteries of at least 2.0 mm diameter with ≥70% untreated obstruction after the index percutaneous coronary intervention and before minimally invasive valve surgery. Results: Complete and incomplete revascularization was achieved in 105 (76%) and 33 (24%) patients, respectively (Table). The patients with incomplete revascularization had a lower ejection fraction, a higher STS score, and more prior myocardial infarctions and multi-vessel coronary artery disease. There were no differences in the post-operative complications, 30-day mortality, or 3-year survival (84 vs. 83%, p=0.68). After a median follow up of 29 months, incompletely revascularized patients had a higher incidence of acute coronary syndrome (2.9 vs. 12.9%, p=0.05). Conclusions: In patients undergoing a staged approach of percutaneous coronary intervention followed by minimally invasive valve surgery, incomplete revascularization did not significantly impact the short or mid-term survival, but was associated with an increased incidence of acute coronary syndrome at follow up.
DNA methylation profiling is a method of choice for molecular verification of pediatric WNT-activated medulloblastomas
Authors: Andrey Korshunov, Felix Sahm, Olga Zheludkova, Andrey Golanov, Damian Stichel, Daniel Schrimpf, Marina Ryzhova, Alexander Potapov, Antje Habel, Jochen Meyer, Peter Lichter, David T W Jones, Andreas von Deimling, Stefan M Pfister, Marcel Kool
Journal: Neuro-Oncology (2018)

Wingless-activated medulloblastoma (WNT MB) represents a well-characterized molecular variant accounting for 10–15% of all MB and is associated with a favorable clinical outcome. Patients with localized WNT MBs could benefit from de-intensification of combined treatment, which would require an accurate diagnosis of these tumors. However, despite the presence of molecular features related with a WNT MB signature (nuclear ß-catenin immunoexpression, CTNNB1 mutation, and monosomy 6), a prompt and reliable diagnostic verification of these tumors is not yet feasible. In the current study, we analyzed 78 samples of WNT MB treated in a single institute through genome-wide DNA methylation and targeted next generation sequencing to elaborate an optimal method for WNT MB molecular verification. We found that DNA methylation profiling discloses significant advantages for molecular diagnostic of WNT MB. All other "routine" methods applied, such as ß-catenin immunohistochemistry, CTNNB1 mutation analysis, and detection of monosomy 6, failed to identify all WNT MB cases. Survival analysis revealed that application of a reduced radiotherapy protocol for WNT MB treatment had no influence on patients' survival. Only one patient died due to local relapse but recurrent tumor was pathologically and molecularly diagnosed as a secondary glioblastoma. DNA methylation analysis should be considered as a method of choice for further clinically relevant stratification of WNT MB and for correct diagnosis of the recurrent tumors. WNT MB patients with localized disease could benefit from treatment de-intensification.
Is there congruence between the types of triggers that cause delight or disgust in cancer care?
Authors: Laura M Holdsworth, Dani Zionts, Steve Asch, Marcy Winget
Journal: Journal of Clinical Oncology (2018)

216 Background: Much of patient satisfaction theory relates to meeting expectations and resolving needs, especially around doctor-patient interactions and the care environment. While there is substantial literature on the correlates of patient satisfaction, few have compared how positive attributes that improve patient satisfaction might create dissatisfaction when negative. The aim of this paper is to explore the symmetry between the types of triggers that delight and disgust patients. Methods: Qualitative analysis of interviews and free-text handwritten survey comments collected in a medical center’s cancer clinics. We created a taxonomy for rating the intensity of attitudes expressed in handwritten comments and verbal data, with the extremes rated as delighters (positive) or disgusters (negative). Results: The main causes of delight for patients related to issues around the technical process of care, such as the technical skills of providers and nurses, and the interpersonal connection and communication with people involved in their care. Causes of disgust were broader, spanning all thematic categories, particularly: insensitive behavior, perceived poor quality technical care or communication, access problems (e.g. wait times, scheduling, and travel), and receiving test results. Handwritten comments related to patient disgust or negativity were frequently longer and included rich description, whereas delights were often brief and usually indicated people or attributes perceived as delightful, such as ‘caring, ‘friendly’, and ‘compassionate’. Conclusions: While issues of provider/staff skill and interpersonal relationships caused both delight and disgust, there was a lack of congruence between more systemic or mundane features of care which did not contribute to delight, but did feature in disgust. This suggests that there are normative expectations around systemic issues that appear invisible when they occur as expected, but are apparent only when negative. The implication for patient satisfaction models is that interpersonal and technical aspects of care might be weighted more heavily by patients, but that any aspect of the health care encounter may be important when it is negative.
Improving the Medical Orders for Life-Sustaining Treatment (MOLST) form documentation process in an outpatient oncology clinic.
Authors: Jennifer Faig, Jessica A. Zerillo, Danielle Wright, Aya Sato-DiLorenzo, Michelle Mahony, Charlene Mantia, Rolando Salazar, Carol O'Leary, Mayca Nguyen, Mary K. Buss
Journal: Journal of Clinical Oncology (2018)

299 Background: Advance care planning is an important aspect of providing high quality care to oncology patients. ASCO Quality Oncology Practice Initiative (QOPI) recognizes the importance of advance directive documentation as a quality measure. MOLST forms are often completed to document a patient’s preferences for medical care at the end of life. The primary objective of this study was to improve the MOLST form documentation process in an outpatient solid tumor oncology clinic. Methods: We conducted a survey to identify areas for improvement and created a process map illustrating the complexities of the current MOLST form documentation process. A multidisciplinary team comprised of physicians, nurses, administrative staff, a quality improvement leader and a palliative care expert was created to focus on this initiative. We developed a new process whereby completed MOLST forms were uploaded into the electronic medical record (EMR) system. We implemented the following interventions: 1) made MOLST forms accessible to clinicians; 2) created a centralized location to place MOLST forms; 3) educated oncology staff about the new process; and 4) streamlined the MOLST form scanning process into the EMR. This process was studied during a pilot between January 22, 2018-February 2, 2018. A pre-pilot convenience sample was compared to pilot data. Results: Oncologists identified the need to improve the MOLST form documentation process on the pre-pilot survey. The percentage of completed MOLST forms scanned into the EMR increased from 44.4% (4 out of 9 forms) pre-pilot to 87.5% (7 out of 8 forms) during the pilot (p = 0.06). All of the MOLST forms completed using the new process were scanned into the EMR. Physician satisfaction with the MOLST process increased from 7.1% (2 out of 28 survey respondents) pre-pilot to 87.5% (14 out of 16 survey respondents) post-pilot (p &lt; 0.01). Conclusions: A targeted process to enhance the documentation of completed MOLST forms succeeded and increased physician satisfaction. Further work will need to be performed to better identify oncology patients appropriate for MOLST form discussions.
Tele-oncology at MSK: Delivering innovative, patient-centered care.
Authors: Christian Otto, Jennifer Wang, Chasity Walters, Mark E. Robson, William Breitbart, Kylie Cotter, Jashonna Harris, Megan Harlan Fleischut, Youngho Paul Kim, Reggie Saldivar, Judith Eve Nelson, Robert Sidlow
Journal: Journal of Clinical Oncology (2018)

272 Background: MSK is deploying teleoncology solutions that improve the patient experience, quality of care, and enhance patient access. MSK’s teleoncology mission is to utilize digital technology as a mainstream channel for connected care across the cancer continuum. Methods: Teleoncology programs were established between Manhattan and four regional sites in support of Psychiatry, Genetic Counseling, and Supportive Care. MSK’s “Virtual Programs” delivered tele-education and tele-support to patients and caregivers in their home or place of work to prepare them for each stage of their care. Patient acceptability ratings were evaluated for quality of care, ease of use, interaction quality, and satisfaction and future use. Results: The four programs generated 7563 teleoncology visits. Virtual Programs served 3865 patients over 766 sessions. Fifty-eight percent (N = 2269) of patients participated in group education sessions (8.3±1.2 patients per session), while 41.3% (N = 1596) participated in support groups (3.2±0.3 patients per session). Overall, 60% of Virtual Program sessions were delivered to patients at home, and 20% to patients at work. Tele-genetics counseling was provided to 3516 patients. The majority of tele-genetics sessions occurred at regional sites (61.4%). Thirty-eight patients completed 159 telepsychiatry visits (4.2±5.8 visits/patient). In Supportive Care, 23 patients completed 38 visits (1.6±1.4 visits/patient). Patients saved 95 minutes of travel time per teleoncology visit. Acceptability ratings for teleoncology were collected from 1185 patients (15.7%). Ninety-one percent of patients were satisfied or extremely satisfied with their teleoncology experience, 95.6% with the information they received, 94.4% with the skill of the provider, and 86.3% with the ease of use of the teleoncology platform. Conclusions: Teleoncology offers an innovative means of providing cancer care to patients by decreasing the stress of travel, missed work, and caregiver requirements. Patients reported that teleoncology made care more accessible and allowed them to remain in their community with family support. For clinicians, teleoncology expanded patient outreach, and improved patient adherence.
Abstract 20842: Nicotine Replacement Therapy is Safe in Smokers Hospitalized With Acute Coronary Heart Disease
Authors: Quinn R Pack, Aruna R Priya, Tarau Lagu, Penelope S Pekow, Auras R Atreya, Nancy A Rigotti, Peter K Lindenauer
Journal: Circulation (2017)

Background: Little is known about the safety of nicotine replacement therapy (NRT) in smokers hospitalized with acute coronary heart disease (CHD). Methods: We examined the safety of NRT use among ...
Abstract 19676: Diagnostic Performance of Instantaneous Wave-Free Ratio for Intermediate Coronary Artery Stenosis in Patients With Severe Aortic Valve Stenosis
Authors: Futoshi Yamanaka, Koki Shishido, Tomoki Ochiai, Kazumasa Yamazaki, Noriaki Moriyama, Seiji Yamazaki, Sigeru Saito
Journal: Circulation (2016)

Introduction: Fractional flow reserve (FFR) is a standard technique to assess the functional severity of coronary artery stenosis in the catheterization laboratory, whereas the instantaneous wave-free ratio (iFR) is being introduced as a new non-pharmacologic-stress index of coronary stenosis severity. The iFR could have great advantages in patients with severe aortic valve stenosis (AS), to evaluate physiologically intermediate coronary artery stenosis, because iFR measurement does not require pharmacologic stress test. However, its performance has not been explored yet. Hypothesis: The hypothesis and aims of this research is to establish best cut off iFR value for FFR ≤0.8 in intermediate coronary artery stenosis in patients with severe AS. Methods: This clinical research launched from Feb 2015. This data was prospectively obtained from multicenter registry and interstitial review board approved in each center. Severe AS was defined an aortic valve area less than 1.0 cm2, a mean aortic valve gradient of...
Abstract 12107: Worsening of Mitral Regurgitation During Off-pump Coronary Artery Bypass Grafting Causes Hemodynamics Deterioration by Dislocation of Beating Heart in Patients With Ischemic Heart Disease
Authors: Masumi Iwai-Takano, Tsuyoshi Fujimiya, Takashi Igarashi, Shinya Takase, Hitoshi Yokoyama
Journal: Circulation (2016)

Introduction: Worsening of mitral regurgitation (MR) during off-pump coronary artery bypass grafting (OPCAB) is one of the predictors, which is often observed during elevation and dislocation of the beating heart in patients with ischemic heart disease (IHD). It is considered that morphological changes of mitral valve complex and worsening of MR cause the hemodynamic deterioration during OPCAB. However, it remains unclear whether the worsening of MR causes the hemodynamic deterioration during OPCAB. Hypothesis: The dislocation of the beating heart during OPCAB leads to exacerbation of ischemic MR, and the worsening of MR relates with hemodynamics deterioration. Methods: We enrolled 19 patients with IHD, who did not show significant MR in pre-operative period. All patients undertook OPCAB. During OPCAB, we positioned the beating heart in 4 positions for CABG, i.e., control, LAD-, RCA-, and LCX- positions, using Starfish heart positioner TM and Octopus 2 TM (Medtronic). In each position, we assessed the MR jet area by 2D-TEE and the hemodynamic parameters. We evaluated the relationship the worsening of MR and the hemodynamics deterioration. Results: Among the 4 positions, there was a significantly different in central venous pressure (CVP, Control: 9.6±2.7, LAD: 9.5±2.3, LCX: 10.9±2.4, RCA: 10.2±2.6 mmHg, P&lt;0.01) and stroke volume (SV, Control: 69.1±23.3, LAD: 67.9±19.4, LCX: 52.3±14.4, RCA: 51.7±16.1 ml, P&lt;0.01), but not in mean systemic pressure and mean pulmonary arterial pressure (mPA). The MR jet area was significantly increased in LCX and RCA positions compered to control position (control: 0.8±0.7 to LCX: 2.6±2.7, RCA: 2.0±2.2 cm 2 , each P&lt;0.05). In LCX position, the MR jet area has the relationship with mPA (R=0.51, P&lt;0.05) and SV (R=–0.71, P&lt;0.01). On the other hand, the worsening of MR did not show the relationship with the wall motion score index, the location of asynergy and the hemodynamics before OPCAB. Conclusion: The dislocation of the beating heart during OPCAB (especially LCX and RCA positions) leads to the worsening of MR that relates with hemodynamics deterioration.
Results of a nationwide epidemiologic survey of autosomal recessive congenital ichthyosis and ichthyosis syndromes in Japan
Authors: Michiko Kurosawa, Ritei Uehara, Atsushi Takagi, Yumi Aoyama, Keiji Iwatsuki, Masayuki Amagai, Masaki Nagai, Yosikazu Nakamura, Yutaka Inaba, Kazuhito Yokoyama, Shigaku Ikeda
Journal: Journal of the American Academy of Dermatology (2018)
Pan-Canadian Oncology Drug Review (pCODR): A unique model to support harmonization of cancer drug funding decisions in Canada.
Authors: Maureen E. Trudeau, Alexandra Chambers, Kendra Christiansen, Helen Mai
Journal: Journal of Clinical Oncology (2018)

41 Background: Unlike most other countries, Canada has a dedicated HTA process to review cancer drugs. pCODR, a program of CADTH, conducts thorough and objective evaluations of clinical and economic evidence; as well as considering clinician and patient perspectives, and using this information to make recommendations to the participating jurisdictions to guide their drug funding decisions. Previously, Canadian provinces had separate regional drug review processes to inform their local funding decisions. The pCODR process reduces duplication of effort by individual funders and ensures that reviews are done in a timely and consistent manner. Methods: In a retrospective review, we identified all anticancer drugs reviewed by pCODR from July 2011 to March 2018. Results: As of March 31, 2018, pCODR has issued 103 notifications to implement a final recommendation. Of note, 96% of the submissions include patient group input and 88% of the submissions include clinician input. The median time to complete a review is 146 business days. The pCODR Expert Review Committee has issued 21 negative recommendations, while the remainder were either positive recommendations (n = 10), or conditional recommendations (n = 72). The “condition” that must be addressed most frequently in the conditional recommendations is the cost-effectiveness of the drug. Over 75% of the 82 positive and conditional recommendations have received uptake from one or more participating jurisdictions. The concordance rates are as follows: Conclusions: With the implementation of the pCODR process, there is greater harmonization in cancer drug funding decisions and supports equitable access across Canada.[Table: see text]