tbuckley/cabot-search huggingface dataset:
Prevalence of vitamin D deficiency in Africa: a systematic review and meta-analysis
Authors: Reagan M Mogire, Agnes Mutua, Wandia Kimita, Alice Kamau, Philip Bejon, John M Pettifor, Adebowale Adeyemo, Thomas N Williams, Sarah H Atkinson
Journal: The Lancet Global Health (2019)

BackgroundVitamin D deficiency is associated with non-communicable and infectious diseases, but the vitamin D status of African populations is not well characterised. We aimed to estimate the prevalence of vitamin D deficiency in children and adults living in Africa.MethodsFor this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, African Journals Online, and African Index Medicus for studies on vitamin D prevalence, published from database inception to Aug 6, 2019, without language restrictions. We included all studies with measured serum 25-hydroxyvitamin D (25[OH]D) concentrations from healthy participants residing in Africa. We excluded case reports and case series, studies that measured 25(OH)D only after a clinical intervention, and studies with only a meeting abstract or unpublished material available. We used a standardised data extraction form to collect information from eligible studies; if the required information was not available in the published report, we requested raw data from the authors. We did a random-effects meta-analysis to obtain the pooled prevalence of vitamin D deficiency in African populations, with use of established cutoffs and mean 25(OH)D concentrations. We stratified meta-analyses by participant age group, geographical region, and residence in rural or urban areas. The study is registered with PROSPERO, number CRD42018112030.FindingsOur search identified 1693 studies, of which 130 studies with 21 676 participants from 23 African countries were included in the systematic review and 120 studies were included in the meta-analyses. The pooled prevalence of low vitamin D status was 17·31% (95% CI 9·86–26·27) with a cutoff of serum 25(OH)D concentration less than 30 nmol/L; 34·18% (26·30–42·51) for a cutoff of less than 50 nmol/L; and 58·54% (50·23–66·62) for a cutoff of less than 75 nmol/L. The overall mean 25(OH)D concentration was 68·10 nmol/L (95% CI 64·83–71·37). There was no evidence of publication bias, although heterogeneity was high (I2 ranged from 98·26% to 99·82%). Mean serum 25(OH)D concentrations were lower in populations living in northern African countries or South Africa compared with sub-Saharan Africa, in urban areas compared with rural areas, in women compared with men, and in newborn babies compared with their mothers.InterpretationThe prevalence of vitamin D deficiency is high in African populations. Public health strategies in Africa should include efforts to prevent, detect, and treat vitamin D deficiency, especially in newborn babies, women, and urban populations.FundingWellcome Trust and the DELTAS Africa Initiative.
Bortezomib-Doxorubicin-Dexamethasone as Induction Prior to Reduced Intensity Autologous Transplantation Followed by Lenalidomide as Consolidation/Maintenance in Elderly Untreated Myeloma Patients
Authors: Antonio Palumbo, Patrizia Falco, Francesca Gay, Vittorio Montefusco, Claudia Crippa, Francesca Patriarca, Milena Gilestro, Anna M. Liberati, Fausto Rossini, Tommaso Caravita, Antonietta Falcone, Federica Cavallo, Paolo Corradini, Giuseppe Rossi, Mario Boccadoro
Journal: Blood (2008)
Abstract 375: Acetyl-CoA Production by Specific Metabolites Promotes Cardiac Repair After Myocardial Infarction via Mediating Histone Acetylation
Authors: Ienglam Lei, Shuo Tian, Wenbin Gao, Zhong Wang
Journal: Circulation Research (2019)

In this study, we set out to identify an interlinked metabolic and epigenetic network that produces acetyl-CoA for histone acetylation and gene regulation, and determine whether this network promotes heart repair and protection after I/R injury. Myocardial ischemic reperfusion (I/R) injury induces dramatic metabolic changes and is accompanied with extensive epigenetic changes. Recent studies reveal that energy metabolism and chromatin epigenetics are intimately linked in cellular functions. In particular, acetyl-CoA is a building block for energy metabolism and histone acetylation. However, the acetyl-CoA mediated regulatory machinery integrating metabolic pathways and chromatin modifications has been under-explored in heart repair and protection. We conducted a screen of energy metabolites in promoting histone acetylation and heart repair both in vivo and in vitro. Our screen identified that acetate, pyruvate, and octanoic acid (8C) but not citrate and nonanoic acid (9C) improved heart function after MI in rats. In particular, 8C administration resulted in the most significant heart functional recovery after MI. More importantly, in a more clinically relevant setting, 8C injection at the time of reperfusion 45 minutes after left anterior descending coronary (LAD) ligation showed comparable repair effect to that of 8C administration before LAD ligation, suggesting that 8C could be a very effective metabolic natural product to treat MI. Mechanistically, 8C promoted histone acetylation in CM chromatin after IR injury and inhibited CM death by activating expression of anti-oxidant genes Nrf2, HO1, and NQO1. We further established that the 8C promoted histone acetylation and heart repair was transduced by metabolic enzyme medium-chain acyl-CoA dehydrogenase (MCAD) and histone acetylase GCN5/KAT2A. Therefore, this study has elucidated an interlinked metabolic/epigenetic network comprising 8C, acetyl-CoA, MCAD, and KAT2A in stimulating histone acetylation and anti-oxidative stress gene expression to combat heart injury. This study provides a novel strategy for treating myocardial I/R disease at the interface of metabolism and epigenetics.
Pathways impact on OCM drug cost.
Authors: Valerie Pracilio Csik, Jared Minetola, Karen Walsh, Michael J. Ramirez, Mark Hurwitz
Journal: Journal of Clinical Oncology (2019)

109 Background: Oncology care, including drugs, represents a significant portion of US healthcare spending. Cost of Part B drugs has increased at a rate 5.7x that of overall Medicare spending (1997-2004). As a participant in the Oncology Care Model (OCM), we found drug costs represent a majority of our total costs. To reduce treatment (Tx) variability, our NCI-designated cancer center chose to implement pathways. Pathways are a clinical decision-support tool that use evidence-based care maps accounting for efficacy, toxicity and cost. At one institution, use of pathways contributed to $15k in savings for stage IV lung cancer Tx. We hypothesized pathway driven Tx standardization would favorably impact total chemotherapy (CTx) costs at the implementation site. Methods: In July 2018, we implemented pathways in Medical and Radiation Oncology for new starts or changes in Tx. Oncologists accessed the tool through our EMR, selected and placed orders for Tx. OCM quarterly data was used to compare 2 quarters immediately pre- and post-pathway implementation. The cancer-mix-adjusted Per-Member-Per-Month (PMPM) Allowed Amounts for CTx were compared between 3 groups; patients on-pathway, patients off-pathway and patients for which the pathways tool was not used (no utilization). PMPMs were evaluated pre- and post-implementation and an ANOVA test was used to evaluate significance of the difference between the two periods. Results: PMPM CTx costs decreased 4.6% between pre- and post-pathway implementation when oncologists followed pathways. By comparison, the off-pathway cohort and the no utilization groups had increases of 0.9% and 17.7% respectively. An evaluation of cost difference proved significant (p &lt; .0001). Breast patients on-pathway had a cost decrease of 20%, compared to increases of 32% and 11% for off-pathway and no utilization groups, respectively. Conclusions: Pathway use reduced variation, a known contributor to healthcare costs, and therefore may be an effective cost control tool. Additional quarters of claims data is needed post-implementation to fully define the impact of pathways on total cost. [Table: see text]
Successful implementation of a quality improvement intervention towards a QOPI-compliant breast cancer center in Mexico.
Authors: Omar Peña-Curiel, Cynthia Villarreal-Garza, Mauricio Canavati-Marcos, Karen M. Velazquez-Ayala, Janeth Castro-Carrasco, María Alejandra Garza-Ledezma, Katia Zarzar-Handal, Héctor Díaz-Pérez, David Omar Rodriguez, Vedner Guerrier
Journal: Journal of Clinical Oncology (2019)

59 Background: Ensuring quality of care in our breast cancer center (BCC) at Hospital Zambrano Hellion in Monterrey, Mexico has been one of the main objectives since its commencement in 2016. To achieve this goal, we evaluated our compliance to ASCO’s Quality Oncology Practice Initiative (QOPI) 84 breast cancer related metrics as a part of a quality improvement (QI) project undertaken during the 2018 Quality Training Program (QTP) in Alexandria, VA. Methods: We established a multidisciplinary QI team engaged in data acquisition, process improvement and implementation in our BCC. We developed a Microsoft Word medical record template and established a new “first time visit” model to achieve our objective of 80% documentation rate of 13 identified reasonably achievable QOPI metrics. Monthly Plan-Do-Study-Act cycles were conducted for 6 months from August through December 2018. Results: After a sample data abstraction of 20 patients’ medical records, our baseline QOPI-compliance resulted in 40/84 QOPI metrics being met by our BCC program. The remaining 44/84 were distributed in two categories, the first 13/44 were labeled as “done/not documented” metrics, and the second set of 31/44 metrics were labeled as “not done/not documented” metrics given they were not performed at all. We approached the 13/44 “done/not documented” metrics for this project based on our priority matrix. After our QI intervention, we surpassed our objective by the third PDSA cycle. Furthermore, by March 2019 we reached 95% cumulative compliance of those metrics. Conclusions: The development of a systematic QI approach enhanced our BCC QOPI-compliance in 13 reasonably achievable metrics to 95% over a 6-month period. Currently, we are targeting the remaining 40/84 metrics to ultimately adhere to all breast cancer QOPI standards. To our knowledge, we are the first Mexican BCC pursuing a QOPI-compliant practice through ASCO’s QTP initiative.
Functional Screening Of Oncomir-196b-RISC Captured Targets Reveal Mir-Inhibition Of Tumor Suppressor Activity In MLL-AF9 Mediated Leukemogenesis
Authors: Sara E. Meyer, Rogers M. Andrew, Bruce J Aronow, Kakajan Komurov, Ashish Lal, Judy Lieberman, H. Leighton Grimes
Journal: Blood (2013)
Long Term Survival Analysis of Multiple Myeloma Patients Receiving Induction Therapy+ Autologous STEM CELL Trasplantation, Comparing Velcade-Dexametasone to Alkylating Polichemotherapy As Induction Therapy
Authors: Sara Caceres, Rocio Cardesa, Carmen Cabrera, M. Helena Bañas, Fatima Ibañez, Julio Prieto, Jorge Groiss, Damian Toran, Carmen Hernandez, Ortegon Sergio, Duvos Elena, Maria Soledad Casado, Esperanza Cerezo, Raul Siguenza, Sara Suarez-Varela, Fernando Carnicero, Maria Luisa Martin Mateos, Maria J. Arcos, Angel Rodriguez, Baldomero Moriano, Ignacio Casas, Francisco Perez Leal, Teresa Vazquez Godoy, Jose M. Bagace, Miguel A. Sanz, Juan Miguel Miguel Bergua Burgues
Journal: Blood (2018)
Using a geographic and interdisciplinary strategy to improve patient care outcomes.
Authors: Tony Philip, Corey Karlin-Zysman, Alex Rimar, Tara Liberman, Donna Cardoza, Jane E. Carleton, Craig E. Devoe
Journal: Journal of Clinical Oncology (2019)

78 Background: Long Island Jewish Medical Center at Northwell Health is an urban/suburban academic tertiary care hospital located across the street from the Northwell Health Cancer Institute. The Division of Hospital Medicine partnered with Hematology/Oncology and Palliative Care to co-manage inpatient oncology patients on a geographic unit. The goal was to improve patient care through co-ownership and co-accountability of cancer patients in conjunction with a unit-based collaboration with Nursing, Pharmacy, Social Work, Case Management and Physical Therapy. Methods: A unit-based, interdisciplinary care team was formed consisting of Medical Oncologists, Hospitalists, Palliative Care specialists, Radiation Oncologists, as well as unit based and specialty trained nurses, social workers and advanced care practitioners. The team meets Monday thru Friday during interdisciplinary rounds to collaboratively discuss the care plans of each patient. We recently added a hospital-based medical oncologist to support greater continuity and communication. Results: Since full implementation including improvements in patient cohorting, the oncology care model has resulted in a 20% reduction in Medicare readmissions, a significant reduction in CAUTIs and CLABSIs, a 50% reduction in C.diff, a decreased CMI-adjusted length of stay and an improvement in pain management HCAHP scores, despite a 10% increase in CMI. An interdisciplinary approach has also improved documentation of goals of care discussion from 6% to 40-58%, furthering the idea of providing a unified medical voice to a vulnerable population. Conclusions: The oncology care model highlights that implementing multidisciplinary rounding, co-management and population-based geography can deliver a higher quality and more efficient level of care even in the face of higher patient acuity.
Long-Term Outcomes of Arteriovenous Fistulas with Unassisted versus Assisted Maturation: A Retrospective National Hemodialysis Cohort Study
Authors: Timmy Lee, Joyce Zhang Qian, Yi Zhang, Mae Thamer, Michael Allon
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Before successful use in dialysis, many arteriovenous fistulas (AVFs) require one or more endovascular or surgical interventions to assist clinical maturation. However, the effect of assisted maturation on long-term postmaturation AVF outcomes is poorly studied. In this retrospective analysis, the authors analyzed the US Renal Data System to identify elderly patients who underwent AVF creation after initiation of hemodialysis, and whose AVF was used successfully for dialysis with or without assisted maturation. Their analysis of the relationship between the number of prematuration AVF interventions and postmaturation AVF outcomes found a positive association between the number of prematuration interventions and the likelihood of primary patency loss and frequency of interventions after maturation. These findings highlight the high burden of costly interventions to assist clinical maturation for successful AVF use. Background About half of arteriovenous fistulas (AVFs) require one or more interventions before successful dialysis use, a process called assisted maturation. Previous research suggested that AVF abandonment and interventions to maintain patency after maturation may be more frequent with assisted maturation versus unassisted maturation. Methods Using the US Renal Data System, we retrospectively compared patients with assisted versus unassisted AVF maturation for postmaturation AVF outcomes, including functional primary patency loss (requiring intervention after achieving AVF maturation), AVF abandonment, and frequency of interventions. Results We included 7301 patients ≥67 years who initiated hemodialysis from July 2010 to June 2012 with a catheter and no prior AVF; all had an AVF created within 6 months of starting hemodialysis and used for dialysis (matured) within 6 months of creation, with 2-year postmaturation follow-up. AVFs matured without prior intervention for 56% of the patients. Assisted AVF maturation with one, two, three, or four or more prematuration interventions occurred in 23%, 12%, 5%, and 4% of patients, respectively. Patients with prematuration interventions had significantly increased risk of functional primary patency loss compared with patients who had unassisted AVF maturation, and the risk increased with the number of interventions. Although the likelihood of AVF abandonment was not higher among patients with up to three prematuration interventions compared with patients with unassisted AVF maturation, it was significantly higher among those with four or more interventions. Conclusions For this cohort of patients undergoing assisted AVF maturation, we observed a positive association between the number of prematuration AVF interventions and the likelihood of functional primary patency loss and frequency of postmaturation interventions.
Oncologist decision drivers in stage III non-small cell lung cancer: Outcomes of a web-based survey.
Authors: Adam Yagui-Beltran, Kellie Ryan, Marnie L. Boron, Ion Cotarla, Daryl S. Spinner, Eric C. Faulkner, Marissa C. Carroll, Surbhi Shah, Shawna L. Cullen
Journal: Journal of Clinical Oncology (2019)

35 Background: Clinical guidelines seek to optimize patient care. We investigated how oncologists manage stage III non-small cell lung cancer (NSCLC) patients from diagnosis through treatment decision-making and drivers impacting guideline adherence. Methods: A sample of US medical oncologists (n=150) participated in a 38-question, 25-min web-based quantitative survey in January 2019. Participation required at least 3 yrs in practice and 3 stage III NSCLC patients treated in the prior 6-mo period. Results: Surveyed oncologists (82% community; 18% academic), on average, had 15 yrs of clinical experience and treated 20 stage III NSCLC patients in the prior 6 mos. Time from first treatment decision to initiation averaged &gt;2–4 wks in 31% and &gt;4 wks in 20% of patients, respectively. Oncologists recommend definitive concurrent chemoradiation therapy (cCRT) in 48% of unresectable stage III NSCLC patients. Reasons for not recommending cCRT include patient unlikely to tolerate cCRT (64% of oncologists), presence of a targetable mutation (41%), patient inability to travel consistently to receive treatment/inconvenient dosing (41%), and patient cost/affordability (34%). Eighteen percent of unresectable stage III NSCLC patients decline recommended cCRT. Fifty-five percent of patients who receive cCRT go on to receive consolidation immunotherapy (IO). Insurance challenges led to oncologists not recommending consolidation IO in 19% of patients. In the 85% of oncologists who conduct EGFR or PD-L1 testing, positive EGFR or negative PD-L1 tests are reasons for not recommending consolidation IO in 27% of patients (12% and 15%, respectively). Over half (55%) of unresectable stage III NSCLC patients who receive definitive cCRT also receive consolidation chemotherapy, which is no longer recommended in guidelines. Patients receiving consolidation CT were less likely to receive consolidation IO than the overall cohort of patients receiving cCRT (42% vs. 55%). Conclusions: Oncologists reported important variances in guidelines and standards of care related to the stage III NSCLC patient treatment journey. While some deviations from both are expected, there may be areas of focus for quality improvement initiatives.
Abstract 800: HECT Domain Containing-3 (HECTD3) is a Novel Regulator of Cardiac Hypertrophy and Inflammation
Authors: Ashraf Y Rangrez, Ankush Borlepawar, Nesrin Schmiedel, Lynn Christen, Anushka Deshpande, Alexander Bernt, Manju Kumari, Anca Remes, Andreas Helbig, Andreas Jungmann, Samuel Sossalla, Andreas Tholey, Oliver Mueller, Derk Frank, Norbert Frey
Journal: Circulation Research (2019)

Objective: In this study, using a Yeast two-hybrid screen, we identified the HECT domain-containing E3 ubiquitin ligase 3 (HECTD3) as one of the novel cardiac binding partners of SUMO2. Present study thus focusses on deciphering the cardiac function of HECTD3. Methods and Results: HECTD3-SUMO2 interaction was further validated by co-immunoprecipitation analysis. Interesting, adenovirus-mediated overexpression of HECTD3 in neonatal rat ventricular cardiomyocytes (NRVCMs) resulted in downregulation of endogenous as well as overexpressed SUMO2. Proteasome inhibitor MG132 treatment however inhibited HECTD3-mediated SUMO2 downregulation, suggesting SUMO2 as a likely substrate of HECTD3 in ubiquitin-proteasome system dependent protein degradation. To get further insights into cardiac substrates of HECTD3, we performed mass-spectrometry analysis of NRVCM protein lysate. Interestingly, several proteins from interferon signaling, including signal transducer and activator of transcription-1 (STAT1), were significantly downregulated by HECTD3 overexpression. Functional dissection of HECTD3-SUMO2-STAT1 interaction revealed attenuation of cellular hypertrophy and LPS mediated activation of inflammatory cascade in NRVCMs. Importantly, in vitro findings were consistent in vivo , where, AAV-9 mediated overexpression of HECTD3 substantially reduced cardiac hypertrophy and fibrosis, inhibited activation of STAT1-mediated downstream signaling, and attenuated infiltration of inflammatory cells to the heart after transverse-aortic constriction or Angiotensin II treatment. Conclusions: In conclusion, we describe here a novel cardioprotective mechanism involving the ubiquitin ligase HECTD3, which exerts anti-hypertrophic and anti-inflammatory effects via dual regulation of SUMO2 and its sumoylation target STAT1. This “dual pathway” inhibition may be exploited for the prevention and/or therapy of cardiac hypertrophy and heart failure.
Abstract 251: Mitochondrial Calcium Uniporter Regulates Proliferative Activity of Cardiac Fibroblasts Under Angiotensin II Stimulation
Authors: Bong S Jhun, Yuta Suzuki, Michael W Cypress, Peng Zhang, Ulrike Mende, Jin O-Uchi
Journal: Circulation Research (2019)

Introduction: Cardiac fibrosis persists in patients with heart failure (HF) even during treatment with conventional HF therapies designed to control volume/pressure overload and restore cardiomyocyte function. This suggests a critical need to develop novel and effective anti-fibrotic therapies specifically targeting cardiac fibroblasts (CFs). CFs contribute to pathophysiological remodeling such as cardiac fibrosis after cardiac injury and/or during repair in response to various profibrotic stimuli in vivo such as angiotensin II (Ang II). Oxidative stress promotes pathological CF proliferation, but the detailed molecular mechanisms linking mitochondria and CF proliferation remain unclear. Hypothesis: Ang II stimulation promotes mitochondrial ROS (mROS) generation via mitochondrial Ca 2+ (mCa 2+ ) uptake, which subsequently activates mROS-dependent proliferative signaling in CFs. Methods: In CFs isolated from rat hearts, mCa 2+ uptake, mROS levels and mitochondrial morphology were measured using confocal microscopy with a mitochondria-targeted Ca 2+ biosensor mtRCamp1h, a mitochondrial superoxide-sensitive dye MitoSOX, and mitochondria-targeted GFP, respectively.. Results: Ang II (≥1 μM) stimulation induces Ca 2+ release from the endoplasmic reticulum (ER) followed by increased mCa 2+ , mROS, and mitochondrial fragmentation. In addition, Ang II activates ERK1/2- and p38-mediated proliferative pathways, which was inhibited by pretreatment with losartan, an Ang II receptor antagonist. Overexpression of a dominant-negative mCa 2+ uniporter (MCU) with pore domain mutations abolished Ang II-mediated mCa 2+ uptake and mROS generation, and prevented the activation of proliferative pathways. Pretreatment with a mitochondria-targeted antioxidant, mitoTEMPO, also significantly inhibited Ang II-mediated activation of the proliferative pathways without affecting ER-Ca 2+ release or mCa 2+ -uptake. Conclusion: The mROS generation via mCa 2+ accumulation and mitochondrial fragmentation resulting from Ang II stimulation activates mROS-dependent proliferative signaling pathways in CFs. The MCU-dependent mROS generation may serve as an important molecular switch for CF proliferation during cardiac stress.
Prognostic Significance of FDG-PET/CT on Determining Upfront Autologous Stem Cell Transplantation for the Treatment of Peripheral T Cell Lymphomas
Authors: Seo-Yeon Ahn, Seung-Yeon Jung, Sung-Hoon Jung, Jae-Sook Ahn, Je-Jung Lee, Hyeoung-Joon Kim, Sae-Ryung Kang, Yeon-Hee Han, Jae-Yong Kwak, Ho-Young Yhim, Deok-Hwan Yang
Journal: Blood (2018)