tbuckley/cabot-search huggingface dataset:
Myeloablative busulfan/melphalan (BuMel) consolidation following induction chemotherapy for patients with high-risk neuroblastoma: A Children’s Oncology Group (COG) study.
Authors: Meaghan Granger, Gregory A. Yanik, Arlene Naranjo, Jeannine S. McCune, Steven G. DuBois, Rochelle Bagatell, Brian D. Weiss, Stephan A. Grupp, Sheena Cretella Tenney, Shahab Asgharzadeh, Michael D. Hogarty, Joseph Ezra Panoff, John Han-Chih Chang, Julie M Gastier-Foster, Denise Mills, Julie R. Park
Journal: Journal of Clinical Oncology (2016)

10528 Background: The COG conducted a groupwide study of a Busulfan/Melphalan (BuMel) myeloablative regimen in patients with newly diagnosed, high-risk neuroblastoma (ANBL12P1). Previously used in SIOP-EN studies, this is the first trial using BuMel following a COG induction platform. The primary objective was regimen-related toxicity, with a specific focus on pulmonary and hepatic events. Methods: Five cycles of induction were administered, followed by intravenous busulfan (daily, days -6 to -3), melphalan (140mg/m2, day -1) and stem cell rescue. Age and weight based dosing were used for busulfan administration. First dose busulfan pharmacokinetics were mandated and adjustments made to target an AUC <5500 (micromole/liter)*minute. Following hematologic recovery, patients were eligible to receive external beam radiotherapy to primary and residual metastatic sites and then proceed to maintenance immunotherapy. Unacceptable pulmonary toxicity was defined as Grade 4 pulmonary events (CTCAEv.4.0). Sinusoidal Obstructive Syndrome (SOS) was a composite definition using Baltimore criteria. Results: Between 4/2013 and 4/2015, 150 patients were enrolled. One hundred thirteen patients were evaluable for end-induction response assessment, with 27 (25%) CR, 27 (24%) VGPR and 39 (35%) PR, for an overall response rate of 82%. At the time of consolidation, 101 patients are evaluable for toxicity. The incidence of unacceptable pulmonary toxicity was 3.0% (n = 3), SOS 5.9% (n = 6), and combined hepato-pulmonary toxicity 8.9% (N = 9) during consolidation (days 0–28). There were 0 toxic deaths during consolidation. For all subjects (n=98), the median busulfan AUC was 3554 (range: 2360-4555) micromole/liter*minute, with a median AUC of 4558 (range: 3462-5189) micromole/liter*minute for those developing SOS (n =6) and 3232 (range: 3010-5037) micromole/liter*minute for those developing severe pulmonary toxicity (n= 3). Conclusions: BuMel following COG induction regimen is well tolerated with acceptable pulmonary and hepatic toxicity in high-risk neuroblastoma. Clinical trial information: NCT01798004.
Abstract 315: Stromal Cell-derived Factor 1 Protects From Diabetic Cardiomyopathy
Authors: Xiaoqing Yan, Shudong Wang, Jing Chen, Jun Chen, Jun Zeng, Yi Tan
Journal: Circulation Research (2015)

We have demonstrated that stromal cell-derived factor 1(SDF-1) protects against palmitate-induced cardiac apoptosis, which is mediated by NOX-activated nitrosative damage and endoplasmic reticulum stress, via CXCR7, to activate AMPK/p38 MAPK-mediated IL-6 generation (Diabetes 62:2545-2558, 2013). Whether SDF-1 prevents diabetic cardiomyopathy has not been addressed. Here we evaluated the preventive effects of SDF-1 from diabetic cardiomyopathy in a high fat diet plus streptozotocin (HFD/STZ)-induced type 2 diabetic model in C57BL/6J mice. After 1 month on HFD, cardiac function was assayed by echocardiography, and then HFD-fed mice were injected with one low dose STZ (100mg/kg body weight, ip). Five days after STZ injection, mice with blood glucose levels ≥250 mg/dl were defined as diabetic. In parallel, the age-matched normal diet-fed mice injected with a same volume of citrate buffer (pH4.5) were used as control. After onset of diabetes, the mice were maintained on HFD or normal diet for another 4 months with or without SDF-1 treatment. Then cardiac function was assayed again, and the mice were sacrificed and cardiac tissue collected for cardiomyopathic index assay. We found that 1 month HFD feeding induced a significant insulin resistance without effect on cardiac function, but continued HFD feeding after STZ injection significantly impaired cardiac function, which were accompanied by increased insulin resistance and blood glucose, as well as blood insulin, triglyceride and cholesterol levels. Treatment with SDF-1 dose-dependently prevented diabetes-induced cardiac dysfunction but without significant effects on the above mentioned other pathophysiological parameters. These results indicate that SDF-1 possibly prevents diabetic cardiomyopathy via a direct cardiomyocyte action, which needs to be further defined in future study.
Abstract P332: Effects of Intravenous Infusion of Polyunsaturated Fatty Acids and Dextrose on Blood Pressure and Endothelial Function in Obese Subjects
Authors: Aidar R Gosmanov, Dawn Smiley, Joselita Siquiera, Gonzalo Robalino, Limin Peng, Guillermo E Umpierrez
Journal: Circulation Research (2011)

Hyperglycemia and elevated free fatty acids (FFAs) are implicated in the development of hypertension and endothelial dysfunction. We recently reported that 8-hour infusion of soy-bean oil containing polyunsaturated fatty acids (Intralipid) results in the elevation of blood pressure (BP) and endothelial dysfunction in obese healthy subjects. However, the effects of dextrose infusion or combination of dextrose and Intralipid on BP, endothelial function and insulin action are not known. Accordingly, we compared the effects of 8-hour infusion of normal saline at 40 ml/hr, Intralipid 20% at 40 mL/hr, dextrose 10% at 40 ml/hr and combination of Intralipid and dextrose on BP, endothelial function in 12 obese healthy subjects [ages:41±7 yrs, BMI:32±2 kg/m 2 , BP:113/65 mmHg, HOMA-IR: 2.0±1.0]. Blood pressure, brachial artery flow-mediated dilatation (FMD), and levels of FFAs, glucose, and insulin were measured at 0, 4 and 8 h of infusion. Intralipid infusion significantly increased BP, decreased FMD, and increased plasma FFAs (Table). Unlike Intralipid alone, the combination of Intralipid and dextrose did not increase BP but resulted in FMD changes similar to Intralipid alone. Levels of plasma glucose and insulin increased over time after dextrose infusion alone or in combination with Intralipid but not with lipid infusion alone. Compared with Intralipid, the addition of dextrose to Intralipid led to restoration of FFAs to normal level. In summary, Intralipid but not dextrose infusion alone or in combination with Intralipid results in significant elevation in blood pressure in obese healthy subjects. In contrast, dextrose administration had no effect on Intralipid-induced endothelial dysfunction. The mechanisms underlying differences in vascular response after addition of dextrose to Intralipid are not known, but these results indicate that dextrose-induced mild hyperinsulinemia may regulate adverse hemodynamic effects of fat administration in obese subjects.
EZH2 Protein Expression Is Decreased in MDS and MDS/MPN and Correlated with EZH2 Mutation Status, Chromosomal 7 Abnormalities and Clinical Outcome
Authors: Kathy L Mcgraw, Johnny Nguyen, Najla Alali, Jinming Song, David Sallman, Eric Padron, Jeffrey E. Lancet, Daihui Qin, P.K. Epling-Burnette, Lynn C. Moscinski, Rami S. Komrokji, Alan F List, Ling Zhang
Journal: Blood (2016)
Doctors urge Britain to take lead on nuclear disarmament
Authors: Abi Rimmer
Journal: BMJ (2017)

A group of leading doctors and healthcare professionals have called on Britain to work towards multilateral nuclear disarmament.

In a letter to the Daily Telegraph published on 25 July,1 15 doctors and health professionals wrote that Britain should “take a lead in making the world safer” by working towards multilateral disarmament.

The letter’s signatories include Fiona Godlee, editor in chief of The BMJ , Richard Horton, editor in chief of the Lancet , …
Readmissions Have Declined, and Mortality Has Not Increased
Authors: Karen E. Joynt Maddox
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Treating SLAP II lesions with sham surgery
Authors: Dafydd Sion Edwards, Len Funk
Journal: British Journal of Sports Medicine (2017)

We greatly enjoyed reading the most recent article by Shroder et al1 detailing their findings of a well thought out, executed and written-up randomised blinded trial of sham surgery versus labral repair or biceps tenodesis in the surgical management of a SLAP II lesion.

The SLAP lesion, as detailed by the authors, was first described by Snyder et al in 1990.2 The original classification details four distinct lesions of the superior labrum found on shoulder arthroscopy. Since …
Abstract 413: Different Effects Of Organic Nitrates On Endothelial Progenitor Cell Mobilisation And Endothelial Function In Patients With Established Coronary Artery Disease
Authors: Thomas Thum, Volker Wiebking, Georg Ertl, Johann Bauersachs
Journal: Circulation (2008)

Endothelial progenitor cells (EPC) contribute to vascular homeostasis and are in part regulated by nitric oxide (NO). Reduced levels and impaired function of EPC contribute to vascular dysfunction ...
Effects of Homocysteine-Lowering With Folic Acid Plus Vitamin B<sub>12</sub>vs Placebo on Mortality and Major Morbidity in Myocardial Infarction Survivors
Authors: Jane M Armitage, Louise Bowman, Robert J Clarke, Karl Wallendszus, Richard Bulbulia, Kazem Rahimi, Richard Haynes, Sarah Parish, Peter Sleight, Richard Peto, Rory Collins
Journal: JAMA (2010)

Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal.To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes.Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008.2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo.First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization.Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]).Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence.isrctn.org Identifier: ISRCTN74348595.
Manufacturing of graded titanium scaffolds using a novel space holder technique
Authors: Yunhui Chen, Damon Kent, Michael Bermingham, Ali Dehghan-Manshadi, Gui Wang, Cuie Wen, Matthew Dargusch
Journal: Bioactive Materials (2017)

To optimize both the mechanical and biological properties of titanium for biomedical implants, a highly flexible powder metallurgy approach is proposed to generate porous scaffolds with graded porosities and pore sizes. Sugar pellets acting as space holders were compacted with titanium powder and then removed by dissolution in water before sintering. The morphology, pore structure, porosity and pore interconnectivity were observed by optical microscopy and SEM. The results show that the porous titanium has porosity levels and pore size gradients consistent with their design with gradual and smooth transitions at the interfaces between regions of differing porosities and/or pore sizes. Meanwhile, the porous titanium has high interconnectivity between pores and highly spherical pore shapes. In this article we show that this powder metallurgy processing technique, employing the novel sugar pellets as space-holders, can generate porous titanium foams with well-controlled graded porosities and pore sizes. This method has excellent potential for producing porous titanium structures for hard tissue engineering applications.
The Loss of GSTM1 Associates with Kidney Failure and Heart Failure
Authors: Adrienne Tin, Robert Scharpf, Michelle M. Estrella, Bing Yu, Megan L. Grove, Patricia P. Chang, Kunihiro Matsushita, Anna Köttgen, Dan E. Arking, Eric Boerwinkle, Thu H. Le, Josef Coresh, Morgan E. Grams
Journal: Journal of the American Society of Nephrology (2017)

Glutathione S-transferase mu 1 ( GSTM1) encodes an enzyme that catalyzes the conjugation of electrophilic compounds with glutathione to facilitate their degradation or excretion. The loss of one or both copies of GSTM1 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of GSTM1 is also associated with incident kidney failure and heart failure, we estimated GSTM1 copy number using exome sequencing reads in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based prospective cohort of white and black participants. Overall, 51.2% and 39.8% of white participants and 25.6% and 48.5% of black participants had zero or one copy of GSTM1 , respectively. Over a median follow-up of 24.6 years, 256 kidney failure events occurred in 5715 participants without prevalent kidney failure, and 1028 heart failure events occurred in 5368 participants without prevalent heart failure. In analysis adjusted for demographics, diabetes, and hypertension, having zero or one copy of GSTM1 associated with higher risk of kidney failure and heart failure (adjusted hazard ratio [95% confidence interval] for zero or one versus two copies of GSTM1 : kidney failure, 1.66 [1.27 to 2.17]; heart failure, 1.16 [1.04 to 1.29]). Risk did not differ significantly between participants with zero and one copy of GSTM1 ( P &gt;0.10). In summary, the loss of GSTM1 was significantly associated with incident kidney and heart failure, independent of traditional risk factors. These results suggest GSTM1 function is a potential treatment target for the prevention of kidney and heart failure.
Shining a light on burnout
Authors: Navjoyt Ladher
Journal: BMJ (2017)

Last week a photograph of a sign affixed to a faulty vending machine went viral on Twitter, for its perfect description of burnout: "The light inside has broken but I still work." 1 Most doctors experience burnout at some point in their career, so the feeling will familiar to many of us.But the situation is getting worse.Burnout rates among doctors are rising and reaching almost epidemic levels, say Jane Lemaire and Jean Wallace in an editorial (doi:10.
Erratum to: Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma
Authors: Mira A. Patel, Jennifer E. Kim, Debebe Theodros, Ada Tam, Esteban Velarde, Christina M. Kochel, Brian Francica, Thomas R. Nirschl, Ali Ghasemzadeh, Dimitrios Mathios, Sarah Harris-Bookman, Christopher C. Jackson, Christina Jackson, Xiaobu Ye, Phuoc T. Tran, Betty Tyler, Vladimir Coric, Mark Selby, Henry Brem, Charles G. Drake, Drew M. Pardoll, Michael Lim
Journal: Journal for ImmunoTherapy of Cancer (2016)

Unfortunately, after publication of this article [[1][1]], it was noticed that a funding source was not mentioned. Bristol-Myers Squibb was intended to be included in the 'Financial Support' section of the article. 1. 1.[↵][2]1. 2. Patel MA , 3. Kim JE , 4. Theodros D
Randomized Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents in Patients Treated With Percutaneous Coronary Intervention
Authors: Lisette Okkels Jensen, Per Thayssen, Henrik Steen Hansen, Evald Høj Christiansen, Hans Henrik Tilsted, Lars Romer Krusell, Anton Boel Villadsen, Anders Junker, Knud Nørregaard Hansen, Anne Kaltoft, Michael Maeng, Knud Erik Pedersen, Steen Dalby Kristensen, Hans Erik Bøtker, Jan Ravkilde, Richardo Sanchez, Jens Aarøe, Morten Madsen, Henrik Toft Sørensen, Leif Thuesen, Jens Flensted Lassen, Per Thayssen, Lisette Okkels Jensen, Kristian Thygesen, Christian Juhl Terkelsen, Bjarne Linde Norgaard, Morten Madsen, Lars Pedersen, Henrik Toft Sørensen, Per Thayssen, Lisette Okkels Jensen, Hans Henrik Tilsted, Jan Ravkilde, Jens Flensted Lassen, Leif Thuesen
Journal: Circulation (2012)

Background— Among drug-eluting stents released to date, the sirolimus-eluting stent has demonstrated the least amount of late lumen loss, but its efficacy and safety have not been compared head-to-head with the next-generation everolimus-eluting stent. Methods and Results— The Scandinavian Organization for Randomized Trials with Clinical Outcome IV (SORT OUT IV) trial was a randomized multicenter, single-blind, all-comer, 2-arm, noninferiority trial comparing the everolimus-eluting stent with the sirolimus-eluting stent in patients with coronary artery disease. The primary end point was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularization) parameters. The noninferiority criterion was a risk difference of 0.015. Intention-to-treat analyses were done at 9- and 18-month follow-ups. A total of 1390 patients were assigned to receive the everolimus-eluting stent and 1384 patients to the sirolimus-eluting stent. At the 9-month follow-up, 68 patients (4.9%) treated with the everolimus-eluting stent compared with 72 patients (5.2%) treated with the sirolimus-eluting stent experienced the primary end point (hazard ratio, 0.94; 95% confidence interval, 0.67–1.31; P for noninferiority=0.01). At the 18-month follow-up, this differential remained: 99 patients (7.2%) treated with the everolimus-eluting stent versus 105 (7.6%) treated with the sirolimus-eluting stent (hazard ratio, 0.94; 95% confidence interval, 0.71–1.23). At the 9-month follow-up, the rate of definite stent thrombosis was higher in the sirolimus-eluting group (2 patients [0.1%] versus 9 patients [0.7%]; hazard ratio, 0.22; 95% confidence interval, 0.05–1.02). At the 18-month follow-up, this difference was sustained (3 patients [0.2%] versus 12 patients [0.9%]; hazard ratio, 0.25; 95% confidence interval, 0.07–0.88). Conclusion— The everolimus-eluting stent was found to be noninferior to the sirolimus-eluting stent. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00552877.
Wnt5a promotes osteoblastic prostate cancer bone metastases through increasing osteoblastogenesis and invasion
Authors: Jinlu Dai, Chris Hall, June Escara-Wilke, Evan Keller
Journal: Cancer Research (2007)

464   Prostate cancer (PCa) frequently metastasizes to bone, resulting in osteoblastic metastases. We have previously shown that bone morphogenetic proteins (BMPs) promote PCa osteoblastic activity, but upstream inducers of BMP expression in PCa are unknown. Wnts are mediators of osteogenesis. Thus, we investigated a potential role for Wnts in prostate cancer osteoblastic lesions. RT-PCR revealed that the PCa cell line C4-2B, derived from LNCaP cells, expressed multiple Wnts and their receptors. Wnt5a increased BMP4, 6, and 7 mRNA expression in C4-2B cells. Furthermore, Wnt5a activated the BMP 4 and 6 promoters. DKK-1, a Wnt inhibitor, diminished BMP4 and 6 promoter activity in C4-2B cells. Conditioned media (CM) from C4-2B cells induced pro-osteoblastic activity (increased alkaline phosphatase and osteocalcin) in pre-osteoblast cells. DKK-1 diminished partially C4-2B CM-induced pro-osteoblastic activity. In addition to increasing osteoblastogenesis, Wnt5a also increased the invasive ability of C4-2B cell in vitro. This process was blocked partially by DKK-1, or Noggin, a BMP inhibitor. These observations indicate that Wnt5a promotes osteoblastic prostate cancer bone metastases, in part, through induction of BMP activity and their ability to induce osteoblastogenesis and invasion.
Cost saving is nothing to be proud of
Authors: M Justin Zaman
Journal: BMJ (2017)

“Hospitals and other NHS providers ended 2016-17 £791m in the red, down from a £2.4bn deficit in 2015-16 but missing their target of £580m,” summarises Torjesen’s news article on cutting the NHS deficit.1

In the full article, Jeremy Hunt says that the NHS Confederation has achieved “the impossible,” but I …