tbuckley/cabot-search huggingface dataset:
Abstract 13015: Inhibition of Mitochondrial Calcium Uptake in the Heart Does Not Compromise Cardiac Energetics or Function Due to a Preferential Increase in Fatty Acid Oxidation During Increased Cardiac Work
Authors: Tariq R Altamimi, Jennifer Kwong, Arata Fukushima, Jeffery D Molkentin, Gary D Lopaschuk
Journal: Circulation (2016)

The mitochondrial calcium (Ca 2+ ) uniporter (MCU) is primarily responsible for relaying cytosolic Ca 2+ transients to the mitochondria. Increasing cardiac workload by positive inotropes results in increased mitochondrial Ca 2+ , increasing glucose oxidation in comparison to fatty acid oxidation. This has been attributed to Ca 2+ stimulation of pyruvate dehydrogenase, the rate-limiting enzyme in glucose oxidation. We examined what effect increasing workload has on cardiac energetics and cardiac function if mitochondrial Ca 2+ levels are decreased in hearts from inducible cardio-specific deleted MCU (MCU -/- ) mice. Hearts from MCU -/- and MCU fl/fl control mice were isolated and perfused as working hearts with 5 mM glucose, 0.8 mM palmitate, 3% albumin, ± insulin (100 μU/ml) and isoproterenol (10 nM). Surprisingly, MCU -/- hearts showed increased cardiac work (p&lt;0.05 vs. MCU fl/fl ). MCU -/- hearts were also not energy-starved, displaying basal rates of glucose and fatty acid oxidation comparable to controls, and even higher glucose oxidation in response to insulin (3027±213 vs. 2268±166 nmol . g dry wt -1. min -1 in MCU fl/fl , p &lt;0.05). In response to isoproterenol treatment, MCU -/- hearts showed a similar increase in glucose oxidation, compared to controls. However, palmitate oxidation increased to a larger extent in MCU -/- hearts compared to controls (793±60 vs. 558±55 nmol . g dry wt -1. min -1 , p &lt;0.05, respectively), resulting in a greater reliance on fatty acid oxidation for ATP production (40.1±1.9 % vs. 32.7±2.1% in MCU fl/fl , p &lt;0.05). This high fatty acid oxidation supported the higher energy demand at increased workload and provided a higher energy reserve as evident by higher acetyl-CoA/ CoA ratios (0.36±0.03 vs. 0.26±0.02 in MCU fl/fl , p&lt;0.05). The rise in fatty acid oxidation correlated with lower levels of malonyl CoA, an endogenous fatty acid oxidation inhibitor, (4.50±0.29 vs. 8.66±0.98 nmol . g dry wt -1 in MCU fl/fl , p&lt; 0.05), and to an increase in acetylation of the fatty acid oxidation enzyme 3-hydroxyacyl CoA dehydrogenase (which stimulates activity). These results suggest that low mitochondrial Ca 2+ does not compromise cardiac energetics due to a compensatory stimulation of fatty acid oxidation.
Outcomes After Adjustable Gastric Banding—Reply
Authors: Andrew M. Ibrahim, Justin B. Dimick
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Abstract 17181: Association of Intradialytic Hypertension and Mortality According to Responsiveness to Ultrafiltration
Authors: Jason Chou, Elani Streja, Danh Nguyen, Melissa Soohoo, Yoshitsugu Obi, John J Sim, Csaba P Kovesdy, Kamyar Kalantar-Zadeh
Journal: Circulation (2016)

Introduction:  There are mixed data about the association of intradialytic hypertension and mortality in hemodialysis patients. Ultrafiltration (UF) during hemodialysis (HD) can effectively lower blood pressure in some but not all dialysis patients. We hypothesized that intradialytic hypertension that is non-responsive to ultrafiltration has the highest death risk.   Methods:  We examined the association of nadir and change in intradialytic systolic BP (niSBP and ΔiSBP, respectively) with 5-year all-cause (2007-2011) mortality stratified by UF per treatment (defined as Pre-HD minus Post-HD weight) in a cohort of 112,013 incident adult HD patients using Cox regression models adjusted for case-mix, comorbidities, and lab covariates. ΔiSBP was defined as pre-HD SBP minus niSBP.   Results:  We found that as UF increased, patients with niSBP ≥ 140 mmHg had a graded increase in mortality risk (p   Conclusions:  Our results suggest that intradialytic hypertension has a differential mortality risk. We found that intradialytic hypertension that is not reduced by ultrafiltration is associated with an increasingly higher mortality risk. Further studies are needed to identify the optimal niSBP and UF goals and their mechanisms of interaction.
The effect of supplemental estrogen on the outcomes of NSCLC patients in the SEER-Medicare database.
Authors: Samuel P. Heilbroner, Eric Xanthopoulos, Tony J. C. Wang, Simon Cheng
Journal: Journal of Clinical Oncology (2017)

2590 Background: Women with lung cancer have better survival regardless of treatment type. Estrogen has been shown to have cancer-specific and non-cancer effects. However, there is conflicting data on the effect of estrogen hormone therapy on lung cancer incidence and mortality in women. We used the SEER-Medicare database to examine the association of estrogen use with overall and cancer cause specific survival in elderly women with non-small cell lung cancer (NSCLC). Methods: Patients in our cohort were women 65+ years old; were diagnosed with Stage I-IV NSCLC between 2007 and 2012; had Part A and B coverage one year before to one year after diagnosis without supplemental coverage from a HMO; had Part D coverage during the 6 months prior to diagnosis; were not in a nursing home at diagnosis. Using an intention to treat analysis, drug use was defined as having at least one Part D claim for estrogen within six months prior to diagnosis. Event free survival was assessed using a multivariate Cox proportional hazard model accounting for the patient (age, socioeconomic status, race, Charlson score) and tumor (stage, site, histology) characteristics. Results: There were 10,562 patients in our cohort. 688 used estrogen and 9,874 did not. The median age was 75 years with median overall survival of 1.0 year. There was a significant difference in age, socioeconomic status, race, Charlson score, stage, site, and tumor histology between the two groups (p &lt; 0.05 for all). Estrogen use was associated with a significant improvement in overall and cause specific survival on univariate and multivariate regression (see table). Conclusions: Estrogen was associated with a significant improvement in survival. Limitations of this study are inherent to a retrospective claims-based database without knowledge of actual drug use or intent. [Table: see text]
Molecular genetic investigation, clinical features, and response to treatment in 21 patients with Schnitzler syndrome
Authors: Dorota M. Rowczenio, Shelly Pathak, Juan I. Arostegui, Anna Mensa-Vilaro, Ebun Omoyinmi, Paul Brogan, Dan Lipsker, Thomas Scambler, Roger Owen, Hadija Trojer, Anna Baginska, Julian D. Gillmore, Ashutosh D. Wechalekar, Thirusha Lane, Rene Williams, Taryn Youngstein, Philip N. Hawkins, Sinisa Savic, Helen J. Lachmann
Journal: Blood (2017)
NCI-MATCH (Molecular Analysis for Therapy Choice) – a national signal finding trial.
Authors: Barbara A. Conley, Alice P. Chen, Peter J. O'Dwyer, Carlos L. Arteaga, Stanley R. Hamilton, Paul M. Williams, Richard F. Little, Naoko Takebe, David Patton, Kamalia Sazali, Jeffrey Zhang, James A. Zwiebel, Edith P. Mitchell, Robert James Gray, Lisa McShane, Shuli Li, Larry Rubinstein, Keith Flaherty
Journal: Journal of Clinical Oncology (2016)

TPS2606 Background: Certain tumor types show dramatic responses to targeted treatments based on demonstration of the corresponding molecular abnormality. The NCI-MATCH study hypothesizes that patients (pts) across a range of histologies whose tumors share molecular abnormalities that have been shown to respond to a targeted treatment may respond to that same treatment, and that responsiveness or resistance may be predictable by concurrent molecular abnormalities. Methods: Pts with refractory solid tumors or lymphomas have molecular profiling on a proximate biopsy, using a validated, locked next generation sequencing (NGS) assay (143 genes; single nucleotide variants, copy number variants and fusions) and selected other molecular assays. The trial will have > 20 phase II targeted treatments (arms). Drugs are provided by various pharmaceutical companies and could be FDA approved or investigational single agents or combinations. The arms are placed under a “master protocol”, allowing new arms to be added to replace a filled cohort or to add a new molecularly based treatment. Specific rules are established to qualify the selection of the molecular subtype and to select the candidate treatment. A rules engine assigns pts to molecularly targeted treatments based on actionable mutation of interest (aMOI), as well as other factors that inform about likelihood of response. Each arm will enroll 35 pts (one stage design) with appropriate aMOI, regardless of histopathologic tumor type. The primary endpoint is response rate (5% vs 25%). Biopsy is requested upon progression. This trial opened in August 2015. Currently 798 of a planned 3000 patients have been screened. A protocol-directed pause in accrual occurred after 3 months, and interim analysis (feasibility) is ongoing. The current 10 arms and additional arms in the process of being added address molecular abnormalities in: EGFR, ERBB2, PIK3CA, PTEN, ALK, ROS, BRAF, NRAS, NF2, KIT, NF1, SMO, PTCH1, MET, FGFR, AKT, NTRK, cell cycle and PI3K pathway as well as other less common molecular abnormalities. Data from the NCI-MATCH trial is designed to identify signals from molecularly targeted treatment that will inform and accelerate further therapy development leading to clinical benefit. Clinical trial information: NCT02465060.
Abstract 16876: Measuring Thirst in Patients With Heart Failure: The Thirst Distress Scale for Patients With HF is Ready to Use!
Authors: Tiny Jaarsma, Nana Waldréus, Martje van der Wal, Naoko Perkiö Kato
Journal: Circulation (2016)

Introduction: Some heart failure (HF) patients have severe thirst distress. However, there were no validated and reliable instruments to measure thirst distress among HF patients. Aim: To develop a...
Epithelioid Granulomas Associate With Increased Severity and Progression of Crohn’s Disease, Based on 6-Year Follow-Up
Authors: Christopher M. Johnson, Douglas J. Hartman, Claudia Ramos-Rivers, Bhavana Bhagya Rao, Abhik Bhattacharya, Miguel Regueiro, Marc Schwartz, Jason Swoger, Jana Al Hashash, Arthur Barrie, Timothy P. Pfanner, Michael Dunn, Ioannis E. Koutroubakis, David G. Binion
Journal: Clinical Gastroenterology and Hepatology (2017)
Increased Risk of Otitis Media, Pneumonia, and Antibiotic Utilization Following RSV Bronchiolitis Among Infants Born to Mothers With and Without Asthma
Authors: Andrew Abreo, Tan Ding, Cosby A. Stone, Kedir N. Turi, Tebeb Gebretsadik, Pingsheng Wu, Tina V. Hartert
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 19933: Late Fontan Completion Associates with a Reduced Distensibility of the Ascending Aorta in Long-term Fontan Survivors
Authors: Yohsuke Hayama, Hideo Ohuchi, Aya Miyazaki, Satoshi Yazaki, Etsuko Tsuda, Osamu Yamada
Journal: Circulation (2014)

Background: Stiffened and dilated ascending aorta (AAo) before and long after operation, which may be an important predictor of cardiovascular morbidity and mortality has been reported in Fontan pa...
Abstract 20195: NLRP3 Inflammasome Inhibitor Prevents Cardiac Dysfunction Induced by Western Diet in the Mouse
Authors: Salvatore Carbone, Gabriele Adolfo Mauro, Eleonora Mezzaroma, Donatas Kraskauskas, Pascaline Ezouah, Leo Buckley, Raffaella Buzzetti, Benjamin W Van Tassell, Antonio Abbate, Stefano Toldo
Journal: Circulation (2016)

Introduction:  A diet rich in saturated fat and sugars, Western diet (WD), is sufficient to induce cardiac dysfunction in the mouse. Saturated fats and sugars can prime and activate the NLRP3 inflammasome producing cardiodepressant pro-inflammatory cytokines.   Hypothesis:  We hypothesized that administration of an NLRP3 inflammasome inhibitor (NLRP3inh) would prevent WD-induced cardiac dysfunction.   Methods:  Eight week-old CD1 male mice were randomly assigned to either WD (saturated fat 12.8%, sucrose 30%) with (N=10) or without (N=8) 0.15% NLRP3inh 16673-34-0, or Standard Diet (SD)(saturated fat 0.8%, sucrose 0%) with (N=8) or without (N=7) NLRP3inh for 12 weeks. Oral glucose tolerance test (2 g/kg) was performed at baseline and at 12 weeks. Food intake was measured daily and body weight weekly. Transthoracic echocardiography at baseline and 12 weeks was performed to measure interval changes in LV fractional shortening (LVFS), isovolumetric relaxation time (IRT) and myocardial performance index (MPI).   Results:  When compared with SD-fed mice, WD-fed mice had higher daily caloric intake (21±0.5 vs 17±0.9 kcal; p   Conclusions:  The data show, for the first time, that cardiac diastolic dysfunction induced by WD is prevented in mice treated with NLRP3inh in the diet, independent of the effects on body weight or glucose metabolism, suggesting a key role of the NLRP3 inflammasome in the pathogenesis of diet-induced diastolic dysfunction. Further studies in patients with diastolic dysfunction are warranted.
Characteristics Associated With Decreased or Increased Mortality Risk From Glycemic Therapy Among Patients With Type 2 Diabetes and High Cardiovascular Risk: Machine Learning Analysis of the ACCORD Trial
Authors: Sanjay Basu, Sridharan Raghavan, Deborah J. Wexler, Seth A. Berkowitz
Journal: Diabetes Care (2017)

OBJECTIVE Identifying patients who may experience decreased or increased mortality risk from intensive glycemic therapy for type 2 diabetes remains an important clinical challenge. We sought to identify characteristics of patients at high cardiovascular risk with decreased or increased mortality risk from glycemic therapy for type 2 diabetes using new methods to identify complex combinations of treatment effect modifiers. RESEARCH DESIGN AND METHODS The machine learning method of gradient forest analysis was applied to understand the variation in all-cause mortality within the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial (N = 10,251), whose participants were 40–79 years old with type 2 diabetes, hemoglobin A1c (HbA1c) ≥7.5% (58 mmol/mol), cardiovascular disease (CVD) or multiple CVD risk factors, and randomized to target HbA1c &amp;lt;6.0% (42 mmol/mol; intensive) or 7.0–7.9% (53–63 mmol/mol; standard). Covariates included demographics, BMI, hemoglobin glycosylation index (HGI; observed minus expected HbA1c derived from prerandomization fasting plasma glucose), other biomarkers, history, and medications. RESULTS The analysis identified four groups defined by age, BMI, and HGI with varied risk for mortality under intensive glycemic therapy. The lowest risk group (HGI &amp;lt;0.44, BMI &amp;lt;30 kg/m2, age &amp;lt;61 years) had an absolute mortality risk decrease of 2.3% attributable to intensive therapy (95% CI 0.2 to 4.5, P = 0.038; number needed to treat: 43), whereas the highest risk group (HGI ≥0.44) had an absolute mortality risk increase of 3.7% attributable to intensive therapy (95% CI 1.5 to 6.0; P &amp;lt; 0.001; number needed to harm: 27). CONCLUSIONS Age, BMI, and HGI may help individualize prediction of the benefit and harm from intensive glycemic therapy.
Trump says tax bill “essentially repealed Obamacare”
Authors: Owen Dyer
Journal: BMJ (2017)

Donald Trump has claimed that the tax bill passed by the US Senate on 19 December had “essentially repealed” Barack Obama’s signature health law, the Affordable Care Act, and hinted that Republicans had been less than frank with the public about the bill’s healthcare provisions.

“I shouldn’t say this, but we essentially repealed Obamacare,” he said in a speech on the White House lawn celebrating the passage of his party’s tax overhaul. “Obamacare has been repealed in this bill. We didn’t want to bring it up. I told people specifically, ‘Be quiet with the fake news media because I don’t want them talking too much about it.’ Because I didn’t know how people would . . . but now that it’s approved, I can say.”

Shortly afterwards, he added, “We have essentially repealed Obamacare, and we’ll come up with …
Abstract 19243: Using Inpatient Mortality Differential from Weekend Admission to Identify the Role of Hospital Structures: The Case of Ischemic Stroke
Authors: Amresh D Hanchate, Elaine Hylek
Journal: Circulation (2010)

Background:  Although hospitals vary widely in inpatient mortality (IM) from acute stroke, little is known about the influence of hospital structures, i.e., the setting in which care is delivered. We examine this using a unique study design (difference-in-difference estimation) based on exploiting the within-hospital variation in IM between weekday and weekend admissions, thereby attenuating confounding from unobserved differences across hospitals.    Methods:  We merged discharge and American Hospital Association data for all hospitalizations for ischemic stroke (N=257,089) from all hospitals (N=407) from four states (AZ, FL, MA and NJ; 2004-08). We estimated a hierarchical logit IM prediction model, including interactions of weekend admission and hospital structure indicators. The odds ratio (OR) of each interaction (difference-in-difference estimate) compares the excess IM from weekend admission (“excess weekend IM”) for hospitals with a structure (say, bed capacity   Results:  Average hospital IM was 4.7% with interquartile range of 1.0% to 8.9%. Weekend admissions accounted for 25% of all admissions. Average excess weekend IM was +7.5% with hospital interquartile range of -23% to +42%. We examined nine hospital structure indicators (see Table); three structures were associated with significant excess weekend IM - hospitals with a)    Conclusion:  Hospitals with lower bed capacity, higher daily census and higher stroke volume were associated with significant excess IM from weekend admission for ischemic stroke.
CD47 Blockade as an Adjuvant Immunotherapy for Resectable Pancreatic Cancer
Authors: Alex D. Michaels, Timothy E. Newhook, Sara J. Adair, Sho Morioka, Bernadette J. Goudreau, Sarbajeet Nagdas, Matthew G. Mullen, Jesse B. Persily, Timothy N. J. Bullock, Craig L. Slingluff, Kodi S. Ravichandran, J. Thomas Parsons, Todd W. Bauer
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgical resection and adjuvant chemotherapy have an expected survival of only 2 years due to disease recurrence, frequently in the liver. We investigated the role of liver macrophages in progression of PDAC micrometastases to identify adjuvant treatment strategies that could prolong survival. Experimental Design: A murine splenic injection model of hepatic micrometastatic PDAC was used with five patient-derived PDAC tumors. The impact of liver macrophages on tumor growth was assessed by (i) depleting mouse macrophages in nude mice with liposomal clodronate injection, and (ii) injecting tumor cells into nude versus NOD-scid-gamma mice. Immunohistochemistry and flow cytometry were used to measure CD47 (“don't eat me signal”) expression on tumor cells and characterize macrophages in the tumor microenvironment. In vitro engulfment assays and mouse experiments were performed with CD47-blocking antibodies to assess macrophage engulfment of tumor cells, progression of micrometastases in the liver and mouse survival. Results: In vivo clodronate depletion experiments and NOD-scid-gamma mouse experiments demonstrated that liver macrophages suppress the progression of PDAC micrometastases. Five patient-derived PDAC cell lines expressed variable levels of CD47. In in vitro engulfment assays, CD47-blocking antibodies increased the efficiency of PDAC cell clearance by macrophages in a manner which correlated with CD47 receptor surface density. Treatment of mice with CD47-blocking antibodies resulted in increased time-to-progression of metastatic tumors and prolonged survival. Conclusions: These findings suggest that following surgical resection of PDAC, adjuvant immunotherapy with anti-CD47 antibody could lead to substantially improved outcomes for patients. Clin Cancer Res; 24(6); 1415–25. ©2017 AACR.
Sarcoidosis mortality in Sweden: a population-based cohort study
Authors: Marios Rossides, Susanna Kullberg, Johan Askling, Anders Eklund, Johan Grunewald, Elizabeth V. Arkema
Journal: European Respiratory Journal (2018)

We aimed to investigate sarcoidosis mortality in a large, population-based cohort, taking into account disease heterogeneity.Individuals with incident sarcoidosis (n=8207) were identified from the Swedish National Patient Register using International Classification of Disease codes (2003‒2013). In a subset, cases receiving treatment ±3 months from diagnosis were identified from the Prescribed Drug Register. Nonsarcoidosis comparators from the general population were matched to cases 10:1 on birth year, sex and county. Individuals were followed for all-cause death in the Cause of Death Register. Adjusted mortality rates, rate differences and hazard ratios (HRs) were estimated, stratifying by age, sex and treatment status.The mortality rate was 11.0 per 1000 person-years in sarcoidosis versus 6.7 in comparators (rate difference 2.7 per 1000 person-years). The HR for death was 1.61 (95% CI 1.47‒1.76), with no large variation by age or sex. For cases not receiving treatment within the first 3 months, the HR was 1.13 (95% CI 0.94‒1.35). The HR was 2.34 (95% CI 1.99‒2.75) for those receiving treatment.Individuals with sarcoidosis are at a higher risk of death compared to the general population. For the majority, the increased risk is small. However, patients whose disease leads to treatment around diagnosis have a two-fold increased risk of death. Future interventions should focus on this vulnerable group.
Re: Bimal Bhindi, Igor Frank, Ross J. Mason, et al. Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy: A Pathologic Stage-matched Analysis. Eur Urol 2017;72:660–4
Authors: Georgios Papadopoulos, Charalampos Fragkoulis, Konstantinos Ntoumas
Journal: European Urology (2017)