tbuckley/cabot-search huggingface dataset:
CD19 Chimeric Antigen Receptor Therapy for Refractory Aggressive B-Cell Lymphoma
Authors: Caron A. Jacobson
Journal: Journal of Clinical Oncology (2018)

PURPOSE Anti-CD19–directed chimeric antigen receptor (CAR) T-cell therapy has had a resounding effect on the treatment of chemotherapy-insensitive aggressive B-cell non-Hodgkin lymphoma (B-NHL). There are now two US Food and Drug Administration (FDA)–approved products available for treating these patients, and a third product is expected to be approved in the coming months. The question remains: Is there a preferred or best product for my patient? However, answering that question is more complicated than simply balancing the reported efficacy and toxicity results. DESIGN This review outlines potential confounding factors involving the three products and their pivotal clinical trials and highlights additional considerations of manufacturing reliability and overall cost that must be considered when weighing one product against another. It will also review the directions in which the field is moving and strategies being examined to improve efficacy as well as toxicity. CONCLUSION Because a randomized three-arm clinical trial is unlikely, a product may have to be chosen on the basis of results from treatment centers that have experience with all three products. But by the time those results are available, they are likely to be outdated because, given the rapid evolution of the field, the next product will probably have been identified.
Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis
Authors: Qiukui Hao, Malavika Tampi, Martin O’Donnell, Farid Foroutan, Reed AC Siemieniuk, Gordon Guyatt
Journal: BMJ (2018)

Abstract Objective To assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute minor ischaemic stroke or transient ischaemic attack (TIA). Design Systematic review and meta-analysis of randomised, placebo controlled trials. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, ClinicalTrials.gov, WHO website, PsycINFO, and grey literature up to 4 July 2018. Eligibility criteria for selecting studies and methods Two reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. A third team member reviewed all final decisions, and the team resolved disagreements through discussion. When reports omitted data that were considered important, clarification and additional information was sought from the authors. The analysis was conducted in RevMan 5.3 and MAGICapp based on GRADE methodology. Results Three eligible trials involving 10 447 participants were identified. Compared with aspirin alone, dual antiplatelet therapy with clopidogrel and aspirin that was started within 24 hours of symptom onset reduced the risk of non-fatal recurrent stroke (relative risk 0.70, 95% confidence interval 0.61 to 0.80, I 2 =0%, absolute risk reduction 1.9%, high quality evidence), without apparent impact on all cause mortality (1.27, 0.73 to 2.23, I 2 =0%, moderate quality evidence) but with a likely increase in moderate or severe extracranial bleeding (1.71, 0.92 to 3.20, I 2 =32%, absolute risk increase 0.2%, moderate quality evidence). Most stroke events, and the separation in incidence curves between dual and single therapy arms, occurred within 10 days of randomisation; any benefit after 21 days is extremely unlikely. Conclusions Dual antiplatelet therapy with clopidogrel and aspirin given within 24 hours after high risk TIA or minor ischaemic stroke reduces subsequent stroke by about 20 in 1000 population, with a possible increase in moderate to severe bleeding of 2 per 1000 population. Discontinuation of dual antiplatelet therapy within 21 days, and possibly as early as 10 days, of initiation is likely to maximise benefit and minimise harms.
Abstract 18328: Blood Urea Predicts All-cause Mortality in Patients With Severe Aortic Stenosis
Authors: Dan Haberman, Sara Shimoni, Jacob George
Journal: Circulation (2017)

Introduction: Severe Aortic stenosis (SAS) is the most common valvular heart disease in the western world. Various factors are related to SAS prognosis, including chronic kidney disease. Blood urea nitrogen (BUN) is a less specific marker of kidney function than creatinine. However, according to recent studies, elevated BUN is a better prognostic factor in patients with heart failure. Hypothesis: The aim of this study was to evaluate the predictive value of BUN levels on prognosis in patients with SAS. Methods: 142 patients (age 79.1±9.4 years, 88 women) with SAS, were enrolled. The mean valve area was 0.67± 0.17 cm2, the mean and peak gradients were 49±16 mmHg and 77±24mmHG, respectively. The mean NYHA class was 2.6±0.7. 112 patients (79%) underwent percutaneous or surgical aortic valve replacement. Clinical assessment, including diuretic treatment, blood tests and echocardiography were performed at enrollment and follow up visits. The primary endpoint was all-cause mortality. The patient population was ...
Abstract 11430: Clinical Significance of Impaired Vascular Endothelial Function in Patients After Fontan Procedure
Authors: Seiji Asagai, Kei Inai, Hirofumi Tomimatsu, Tokuko Shinohara, Toshio Nakanishi
Journal: Circulation (2014)

Background: It has been reported that patients have reduced vascular endothelial function after Fontan procedure; however, its underlying mechanisms and correlation with exercise capacity are not w...
Microbiota and cancer immunotherapy: in search of microbial signals
Authors: Raad Z Gharaibeh, Christian Jobin
Journal: Gut (2018)

The intestinal microbiota, a conglomerate of microorganisms comprising bacteria, viruses, archaea and fungi, has been recognised as an important component of host physiology through, for example, its influence on nutritional biotransformation, immune response and xenobiotic metabolism.1 These functions are performed via a complexed and multilayer set of controls coming from within the microbial community as well as host factors. Consequently, this intricate microbiota–host partnership is viewed as an essential element of health. For example, intestinal bacterial, fungal and viral composition is different in patients with IBDs and colorectal cancer compared with healthy subjects.2–4 A number of investigative lines probing the impact of microbiota in disease initiation, progression and therapeutics are currently underway. The microbial therapeutic field is particularly dynamic, in part due to the impressive success of faecal microbiota transplantation (FMT) for treatment of recurrent Clostridium difficile infection.5 Whether FMT or derivative synthetic cocktail could be applied to other disease conditions is unclear, and a number of clinical trials for the treatment of metabolic syndrome, diabetes and IBD are currently underway to address this question.

The field of cancer has been particularly attentive to the interaction between bacteria and therapeutics.6 7 This impact of bacteria on therapeutics is wide and includes modulation of chemotherapeutic and immunotherapeutic agents’ efficacy and toxicity via metabolic and immune-mediated mechanisms.8–11 In particular, the recent discovery that intestinal microbiota profoundly impacts responses of patients with cancer to immune checkpoint blockade therapy (Routy  et al ,12 Gopalakrishnan  et al 13 and Matson  et al 14) has attracted much attention. In these studies, the authors used an antibody targeting the coinhibitory receptor/ligand system programmed death-1 (PD-1)/PDL-1 administered to patients with metastatic melanoma13 14 or non-small cell lung cancer and renal cell carcinoma.12 The overall hypothesis pursued by these research teams was …
Intermittent Imatinib Mesylate in Children with Chronic Myeloid Leukemia: Results and Outcome
Authors: Francesco Malaspina, Maria Caterina Putti, Michelina Santopietro, Saverio Ladogana, Rosamaria Mura, Roberta Burnelli, Nadia Vacca, Lorenzo Rizzo, Maria Luisa Moleti, Anna Maria Testi, Andrea Biondi, Franco Locatelli, Giuseppe Saglio, Robin Foà, Fiorina Giona
Journal: Blood (2018)
Guidelines Do Not Proscribe Surgeons Performing Genetic Testing
Authors: Kevin S. Hughes, Peter Beitsch, Steven Chen
Journal: JAMA Surgery (2018)

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
Biomarker microfibril-associated glycoprotein 4 for non-invasive diagnosis and therapeutic evaluation of hepatic fibrosis in patients with hepatitis C
Authors: Young Woo Eom, Soon Koo Baik
Journal: Clinical and Molecular Hepatology (2018)

See the Original "Direct-acting antivirals-based therapy decreases hepatic fibrosis serum biomarker microfibrillar-associated protein 4 in hepatitis C patients" on page 42.
Abstract MP019: Should Global Cardiovascular Risk Guide Treatment of Stage One Hypertension? A Cost-effectiveness Analysis
Authors: Andrew Moran, Petra Rasmussen, Rachel Zhao, Pamela G Coxson, David Guzman, Mark Pletcher, Kirsten Bibbins-Domingo, Lee Goldman
Journal: Circulation (2012)

Introduction: Current U.S. hypertension guidelines base treatment on clinic blood pressure (BP) alone. International guidelines recommend adding global cardiovascular disease (CVD) risk to guide treatment. We projected incremental effectiveness and costs of treating stage 1 hypertension based on CVD risk assessment. Methods: We used the Coronary Heart Disease (CHD) Policy Model, a validated state-transition simulation of the CVD epidemic in the US, to model CHD and stroke events, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness (ICE) of increasingly aggressive treatment of hypertensive patients. Census and national survey data were used to estimate joint distributions of risk factors by age and sex; the CVD risk function was based on Framingham. We modeled treatment of BP to an approximate target &lt;140/90 mmHg using standard dose medications, including averaged annual drug costs (e.g., $253 for a systolic BP reduction of 11.5 mmHg; $1,036 for reduction of 36.7 mmHg) and monitoring costs (2 or 4 visits/year for stage 1 or 2 plus 1 lab test/year for all). We compared a strategy in which only stage 2 hypertensives (≥160/≥100 mmHg) were treated to increasingly aggressive strategies in which stage 1 hypertensives (140-159/90-99 mmHg) with successively lower global CVD risk (15%, 10%, 5% risk, then all of stage 1) were also treated. Results: Reaching hypertension treatment targets with any policy simulated would prevent between 389,000 and 478,000 CVD events annually ( Table ). Treating all stage 2 and ≥15% CVD risk stage 1 hypertensives would be cost-saving and treating stage 1 with ≥10% or ≥5% CVD risk would incur modest costs. Treating all stage 1 would cost $161,000/QALY more than treating only ≥5% CVD risk. Conclusions: Treatment of low risk stage 1 hypertensives appears to come at high cost and limited added benefit unless treatment costs can be minimized. Using global CVD risk assessment might allow re-allocation of resources toward controlling hypertension in the highest risk patients. Table Simulated CVD outcomes, costs, and cost-effectiveness, 2010-2011, the CHD Policy Model Scenario Annual number hypertensives treated Annual CVD events Annual QALYs (millions) Annual costs (millions, $US) ICER * Base case, no intervention - 2,387,000 127.67 $827,313 reference Treat only stage 2 23,364,180 1,997,000 128.78 $825,264 cost saving Treat stage 2 + stage 1 &gt;=15% CVD risk 30,654,361 1,943,000 128.93 $824,541 cost saving Treat stage 2 + stage 1 &gt;=10% CVD risk 34,947,200 1,928,000 128.97 $824,898 $9,381 Treat stage 2 + stage 1 &gt;= 5% CVD risk 44,321,985 1,913,000 129.02 $826,433 $28,931 Treat stage 2 + all stage 1 50,863,390 1,909,000 129.04 $828,290 $160,630 *ICER = difference in cost/difference in QALY in comparison with the next less effective strategy
Abstract MP01: Ideal Cardiovascular Health is Low Among U.S. Workers 45 Years and Older: Results of a National Population-based Cohort Study
Authors: Leslie A MacDonald, Stephen Bertke, Misty J Hein, Suzanne Judd, Sherry Baron, Robert Merritt, Virginia J Howard
Journal: Circulation (2016)

Purpose: We examined the prevalence of ideal cardiovascular health of workers within a national U.S. population-based cohort. Methods: Participants included 5,566 black and white men and women age 45 and older who were employed and free of CHD/stroke when enrolled into the REasons for Geographic and Racial Differences in Stroke Study. Clinical and behavioral cardiovascular risk factor data were obtained at enrollment. Ideal CVH (iCVH) was assessed from seven modifiable CVD risk factors based on the AHA’s Life’s Simple 7. Three clinical (blood pressure (BP), total cholesterol, fasting glucose) and 4 behavioral (physical activity, smoking, diet quality, BMI) factors were each scored according to AHA criteria. Jobs held at enrollment were grouped into aggregate standard occupational groups. National prevalence estimates were computed using SAS Survey Logistic with weights based on actual sampling probabilities of the sub-sample. In significance testing, each occupation group was compared with all other groups combined, adjusting for age, race, sex, and region (stroke-belt, other). Results: The prevalence of iCVH among older workers free of CHD/stroke is low. Although 88% were non-smokers and 78% had ideal glucose, 41% or less achieved ideal levels of all other risk factors. Management/professionals had higher ideal BP and BMI, and were more likely to be non-smokers and physically active; however those employed in business and finance were more likely to have a poor diet (72%). Ideal BP was highest for healthcare practitioners (43%) and those employed in the arts, entertainment, sports and media (47%). Service workers were more likely to have uncontrolled BP, glucose and cholesterol, have lower ideal BMI, and smoke. Uncontrolled BP was high among sales workers (23%) and highest (35%) among those in protective services (e.g., police, firefighters). Dyslipidemia was highest (22%) among personal care and service workers. Obesity was highest among those employed in healthcare support (54%) and food preparation and serving (55%). Those in sales and low status office work were more likely to smoke (17%) and be inactive (38%). Skilled laborers in installation, maintenance and repair had low dyslipidemia (5%), but had the lowest ideal BMI (10%). Transportation and material moving workers had high uncontrolled BP (24%) and the highest smoking prevalence (22%). Conclusions: The prevalence of iCVH among older workers free of CHD/stroke is low, but substantial differences in CVH exist by occupation. Targeted screening and health promotion is warranted to accommodate the information, resource, and schedule needs of older workers employed in diverse occupational settings with different clinical and behavioral risk factor profiles.
Abstract MP028: Physical Activity Relates to Lower Visceral Adiposity in Children and Adolescents
Authors: Amanda E Staiano, Stephanie T Broyles, Alok K Gupta, Peter T Katzmarzyk
Journal: Circulation (2012)

Introduction: Expansion of visceral adipose tissue (VAT) associates with adverse metabolic changes. While regular moderate-to-vigorous activity is associated with lower total body fat in children and adolescents, it is unknown how physical activity relates to other adiposity indices, including VAT. Hypothesis: We hypothesized that regular physical activity in children and adolescents associates with lower body fat, percent body fat, abdominal subcutaneous adipose tissue (SAT), and VAT. Methods: The sample included 393 boys and girls aged 5–18 years (45.6% White, 50.6% African American, and 3.8% Other). Body fat and percent body fat were measured by dual-energy x-ray absorptiometry. Abdominal SAT and VAT mass were measured by magnetic resonance imaging between the highest point of the liver and the lower pole of the right kidney (using 5 to 8 cross-sectional slices, 4.76 cm apart). Participants were categorized as being regularly active by self-report: moderate-to-vigorous physical activity of ≥ 60 minutes/day, ≥ 4 days/week. Those who were physically active fewer than 4 days/week were categorized as not regularly active. Results: In this sample of children and adolescents, 45.6% of participants were regularly active. One-way ANCOVAs adjusted for age and sex demonstrated that regularly active youth had significantly less body fat (p&lt;0.01) and lower percent body fat (p&lt;0.01) than those who were not regularly active. One-way ANCOVAs adjusted for age, gender, and body fat, revealed that regularly active children and adolescents had no difference in SAT but had significantly lower amounts of VAT (p&lt;0.05) when compared to those who were not regularly active. Conclusion: Engagement in moderate-to-vigorous physical activity for at least 60 minutes on four or more days of the week in children and adolescents was related to lower body fat, percent body fat and VAT, when compared to those youth who were less active. The promotion of regular physical activity has significant public health implications for body fat accumulation and for controlling excess VAT during childhood and adolescence.
Patient-Reported Outcomes Over 5 Years After Whole- or Partial-Breast Radiotherapy: Longitudinal Analysis of the IMPORT LOW (CRUK/06/003) Phase III Randomized Controlled Trial
Authors: Indrani S. Bhattacharya, Joanne S. Haviland, Anna M. Kirby, Cliona C. Kirwan, Penelope Hopwood, John R. Yarnold, Judith M. Bliss, Charlotte E. Coles
Journal: Journal of Clinical Oncology (2018)

IMPORT LOW demonstrated noninferiority of partial-breast and reduced-dose radiotherapy versus whole-breast radiotherapy for local relapse and similar or reduced toxicity at 5 years. Comprehensive patient-reported outcome measures collected at serial time points are now reported.
Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models
Authors: Elizabeth A. Killion, Jinghong Wang, Junming Yie, Stone D.-H. Shi, Darren Bates, Xiaoshan Min, Renee Komorowski, Todd Hager, Liying Deng, Larissa Atangan, Shu-Chen Lu, Robert J. M. Kurzeja, Glenn Sivits, Joanne Lin, Qing Chen, Zhulun Wang, Stephen A. Thibault, Christina M. Abbott, Tina Meng, Brandon Clavette, Christopher M. Murawsky, Ian N. Foltz, James B. Rottman, Clarence Hale, Murielle M. Véniant, David J. Lloyd
Journal: Science Translational Medicine (2018)

Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) has been identified in multiple genome-wide association studies (GWAS) as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). On the basis of this genetic evidence, we developed anti-GIPR antagonistic antibodies as a potential therapeutic strategy for the treatment of obesity and observed that a mouse anti-murine GIPR antibody (muGIPR-Ab) protected against body weight gain, improved multiple metabolic parameters, and was associated with reduced food intake and resting respiratory exchange ratio (RER) in DIO mice. We replicated these results in obese nonhuman primates (NHPs) using an anti-human GIPR antibody (hGIPR-Ab) and found that weight loss was more pronounced than in mice. In addition, we observed enhanced weight loss in DIO mice and NHPs when anti-GIPR antibodies were codosed with glucagon-like peptide-1 receptor (GLP-1R) agonists. Mechanistic and crystallographic studies demonstrated that hGIPR-Ab displaced GIP and bound to GIPR using the same conserved hydrophobic residues as GIP. Further, using a conditional knockout mouse model, we excluded the role of GIPR in pancreatic β-cells in the regulation of body weight and response to GIPR antagonism. In conclusion, these data provide preclinical validation of a therapeutic approach to treat obesity with anti-GIPR antibodies.
Abstract P323: Cardiac Rehabilitation is Associated With Decreased Mortality in HIV Patients With Cardiovascular Disease
Authors: Justin M Bachmann, Suman Kundu, Kaku So-Armah, Amy Justice, Jason Sico, Vincent Marconi, Alberta Warner, Adeel Butt, Kris Ann Oursler, Kathleen McGinnis, Matthew Freiberg
Journal: Circulation (2017)

Background: Human immunodeficiency virus (HIV+) patients are at high risk for cardiovascular disease (CVD). While cardiac rehabilitation (CR) reduces mortality in uninfected (HIV-) patients with CVD, there are no specific data on CR use in CVD patients with HIV. Methods: We analyzed data on 7650 veterans (28.4% HIV+) eligible for CR from the Veterans Aging Cohort Study, an observational cohort of HIV+ and HIV- veterans. CR eligibility was defined as a hospitalization for acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, or cardiac valve surgery from 2003-2012, identified using ICD9 and CPT codes. CR use was ascertained from VA and non-VA facilities within one year of discharge from the index CVD hospitalization using CPT codes. We evaluated the association between CR and mortality after adjusting for age, eligibility diagnosis, race, sex, and comorbidities using Cox proportional hazard models. Results: CR use was low in HIV+ and HIV- veterans (9.1% vs. 9.6%, respectively, p=0.06). Among the 7650 CR eligible veterans, there were 2211 deaths over 25,715 person-years of follow-up. Mortality rates were higher among those who did not receive CR, regardless of HIV status (Figure). In adjusted models stratified by HIV status, CR was associated with a significant reduction in mortality for HIV+ (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.26-0.59) and HIV- veterans (HR 0.52, 95% CI 0.42-0.65). Among those receiving CR, HIV was not associated with an increased risk of mortality (Figure) even after adjusting for confounders (HR 1.01, 95% CI 0.63-1.61). Conclusions: CR utilization in both HIV+ and HIV- veterans is low. Participation in CR programs is associated with a significant reduction in mortality, regardless of HIV status. When CR is utilized, however, the risk of mortality is the same for HIV+ and HIV- veterans. CR may be particularly important for reducing mortality in HIV+ patients with CVD.