tbuckley/cabot-search huggingface dataset:
Effect of conventional liver irradiation on the pharmacokinetics of sorafenib through p-glycoprotein: Results of concurrent and sequential strategy.
Authors: Chen-Hsi Hsieh, Tung-Hu Tsai, Yu-Jen Chen, Li-Ying Wang
Journal: Journal of Clinical Oncology (2018)

338 Background: Sorafenib is a multi-kinase inhibitor that demonstrated a significant improved survival of patients with hepatocellular carcinoma (HCC). The efficacy of radiotherapy (RT) concurrent or sequential with sorafenib in unresectable HCC patients has better effects than single agent. However, the mechanism for local RT on sorafenib in the plasma system remains unclear. Here, we evaluate the mechanism of liver irradiation on the pharmacokinetics (PK) of sorafenib using rats as an experimental model. Methods: Free-moving rat model was used in the current study. Image-guided RT with 2 Gy was delivered to the whole liver of Sprague-Dawley rats. The experimental animals were randomized to (A) the sorafenib-only (40 mg/kg, p.o.) group and (B) pre-treated with cyclosporin A [CsA, p-glycoprotein (p-gp) inhibitor, 20mg/kg, i.p. 30 min before RT] group. In each group, the experimental animals were randomized to sham RT (0 Gy with sorafnib), concurrent (after RT 1 hour) and sequential group (after RT 24 hour), respectively. The PK of sorafenib in the plasma system was calculated. Each group’s data was collected from six rats Results: For sorafenib-only group, compared to the sham-irradiated controls, the area under the concentration versus time curve (AUC) of sorafenib was increased by 132% in concurrent group [719 versus (vs.) 1669 min*ug/mL, p = 0.046]. On the contrary, the AUC of sorafenib was decreased by 59% in sequential group (719 vs. 297 min*ug/mL, p = 0.036). Compared to the sorafenib-only group, the AUC of sorafenib in the concurrent group pre-treated with CsA was decreased by 83% (1669 vs. 278 min*ug/mL, p = 0.011). Interestingly, the AUC of sorafenib in the sequential group pre-treated with CsA was increased by 275% (297 vs. 1113 min*ug/mL, p = 0.023). Conclusions: P-pg plays an important role for the PK of sorafenib that was modulated by whole liver irradiation in rodent model. The strategy for modulating the RT-PK phenomenon of sorafenib through p-gp is worth to investigate in the future.
Surgeon who shared his experiences of inappropriate behaviour escapes sanction
Authors: Clare Dyer
Journal: BMJ (2018)

An orthopaedic surgeon who made unwanted sexual advances towards a foundation year one doctor has escaped sanction by a medical practitioners’ tribunal because he later used his case as an example to warn other doctors against harassing colleagues.

Milind Mehta, 48, called the younger doctor into his office at Dr Gray’s Hospital in Elgin, Scotland, in February 2015, ostensibly to show her presentation slides. She had recently told him that her boyfriend in Glasgow had been diagnosed with cancer.

Mehta told her that she “would not be cheating” if she “found someone to confide in” who was not her boyfriend, and that she “needed …
Abstract 16506: A Defect of the Aortic Wall Regenerated by a Novel Warp Knitting Fabric Comprising a Combination of Biodegradable and Non-biodegradable Yarn
Authors: Shintaro Nemoto, Hayato Konishi, Ryo Shimada, Hideaki Yamada, Jun Sakurai, Atsuko Onishi, Kazuteru Kohno, Masaya Ito
Journal: Circulation (2016)

Introduction:  Vascular wall regeneration has been attempted using various types of biodegradable materials and stem cells, but the results have been disappointing.   Hypothesis:  Aortic wall regeneration can be promoted by use of an elaborately designed synthetic cardiovascular patch (OFT patch).   Methods:  The OFT patch is made from an extensible warp-knitted fabric that is a combination of biodegradable (poly-L-lactic acid: PLLA) and non-biodegradable (polyethylene terephthalate: PET) yarn. The fabric was coated with gelatin crosslinked with glutaraldehyde to provide water resistance. The in vitro mechanical properties of the OFT patch were compared with those of currently used surgical patches. Part of the wall of the canine descending aorta was replaced with an OFT patch. The patch was explanted three months later for histological examination.   Results:  The OFT patch had excellent tensile strength, suture retention strength, and bending resistance that were equivalent to those of current patches. The aortic lumen of the explanted OFT patch was covered with smooth intimal tissue. Microscopic examination revealed ideal tissue regeneration characterized by layered smooth muscle cells and collagen fibers with tissue connection across the OFT patch with neo-arterioles in the early stage after implantation. There was little inflammatory reaction and no calcium deposition on the patch yarn, and no aneurysmal or stenotic changes in patch-implanted regions.   Conclusions:  Since the non-biodegradable yarn of the patch is program-designed to expand to quadruple its initial size, the regenerated vascular wall can grow in size as the biodegradable PLLA portion is absorbed. Our results suggest that the OFT patch is suitable for use as a surgical patch in pediatric cardiac surgery.
HEMODYNAMIC AND ECHOCARDIOGRAPHIC COMPARISON AT 1 YEAR OF THE LOTUS AND COREVALVE TRANSCATHETER AORTIC VALVES IN HIGH AND EXTREME SURGICAL RISK PATIENTS: AN ANALYSIS FROM THE REPRISE III RANDOMIZED CONTROLLED TRIAL
Authors: Federico M. Asch, Mani Vannan, Siddharth Singh, Bijoy Khandheria, Stephen Little, Dominic Allocco, Ian Meredith, Ted Feldman, Michael Reardon, Neil Weissman
Journal: Journal of the American College of Cardiology (2018)
<i>What does a geneticist do?</i>
Authors: Fiona Lalloo
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site</i>
Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin
Authors: Alexander Edlich, Pierre Volz, Robert Brodwolf, Michael Unbehauen, Lars Mundhenk, Achim D. Gruber, Sarah Hedtrich, Rainer Haag, Ulrike Alexiev, Burkhard Kleuser
Journal: Biomaterials (2018)
Hepatitis D virus replication is sensed by MDA5 and induces IFN-β/λ responses in hepatocytes
Authors: Zhenfeng Zhang, Christina Filzmayer, Yi Ni, Holger Sültmann, Pascal Mutz, Marie-Sophie Hiet, Florian W.R. Vondran, Ralf Bartenschlager, Stephan Urban
Journal: Journal of Hepatology (2018)
Improving pathology and laboratory medicine in low-income and middle-income countries: roadmap to solutions
Authors: Shahin Sayed, William Cherniak, Mark Lawler, Soo Yong Tan, Wafaa El Sadr, Nicholas Wolf, Shannon Silkensen, Nathan Brand, Lai Meng Looi, Sanjay A Pai, Michael L Wilson, Danny Milner, John Flanigan, Kenneth A Fleming
Journal: The Lancet (2018)
Maternal Microbiota, Prepregnancy Weight, and Mode of Delivery
Authors: Giulia Paolella, Pietro Vajro
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
REMOVING THE LIPOPROTEIN(A)-CHOLESTEROL FROM THE LDL-C MEASUREMENT RESULTS IN A 38% REDUCTION IN PREVALENCE OF ELEVATED LDL-C AT ANY THRESHOLD: IMPLICATIONS FOR THE PREVALENCE AND DIAGNOSIS OF LDL-MEDIATED RISK
Authors: Patrick M. Moriarty, Calvin Yeang, Stephen A. Varvel, Joseph P. McConnell, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2018)
Prevention of Photoreceptor Cell Loss in a Cln6 Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells
Authors: Sophia-Martha kleine Holthaus, Joana Ribeiro, Laura Abelleira-Hervas, Rachael A. Pearson, Yanai Duran, Anastasios Georgiadis, Robert D. Sampson, Matteo Rizzi, Justin Hoke, Ryea Maswood, Selina Azam, Ulrich F.O. Luhmann, Alexander J. Smith, Sara E. Mole, Robin R. Ali
Journal: Molecular Therapy (2018)

The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life of patients, but it is not targeted effectively by brain-directed therapies. Here we set out to explore the therapeutic potential of an ocular gene therapy to treat sight loss in NCL due to a deficiency in the transmembrane protein CLN6. We found that, although Cln6nclf mice presented mainly with photoreceptor degeneration, supplementation of CLN6 in photoreceptors was not beneficial. Because the level of CLN6 is low in photoreceptors but high in bipolar cells (retinal interneurons that are only lost in Cln6-deficient mice at late disease stages), we explored the therapeutic effects of delivering CLN6 to bipolar cells using adeno-associated virus (AAV) serotype 7m8. Bipolar cell-specific expression of CLN6 slowed significantly the loss of photoreceptor function and photoreceptor cells. This study shows that the deficiency of a gene normally expressed in bipolar cells can cause the loss of photoreceptors and that this can be prevented by bipolar cell-directed treatment.
Abstract 16423: Pulmonary Vascular Resistance is a Better Predictor than Pulmonary Artery Pressure of Non-Response to Cardiac Resynchronization Therapy
Authors: Ganesh S Kamath, Ajay Shah, Azhar Supariwala, Sameh Mohareb, Rajeev Joshi, Debbie Kim, Sandhya Balaram, Jonathan S Steinberg, Farooq A Chaudhry
Journal: Circulation (2012)

Background:  Cardiac resynchronization therapy (CRT) is an established therapy modality for advanced heart failure (HF). Despite advances, response rates to CRT remain 50-60%. Pulmonary vascular resistance (PVR) is an independent predictor of HF admission, heart transplantation and all-cause mortality. However, the impact of PVR on response to CRT is not defined.   Methods:  72 pts (68 ± 11 yrs, 43 males, 50% ischemic CMP, EF 18 ± 6 %) with advanced HF (NYHA Class 3.1 ± 0.5) on optimal medical therapy underwent CRT. PVR in Wood Units (WU) was measured using the maximum velocity of tricuspid regurgitant jet (TR max) and VTI of right ventricular outflow tract (RVOT VTI), using the validated formula [TR max/RVOT VTI] x10 +0.16. TR max was used to calculate pulmonary artery pressure (PAP). Left ventricular ejection fraction (LVEF) and LV end systolic volume index (LVESVI) were calculated using modified Simpson’s biplane method during a follow up of 22 ± 12 months. Responders were defined by decrease in LVESVI of 15% from baseline.   Results:  39 pts (54%) were responders and demonstrated significant decrease in LVESVI (85 ± 25 ml/m 2  to 61 ± 19 ml/m 2;  p 2  to 100 ± 27 ml/m 2 ; p=0.12; LVEF 16 ± 6 to 20 ± 11%; p=0.5). PAP (34 ± 12 vs. 37 ± 16; p=0.45) did not differ between the 2 groups but PVR was significantly higher in non-responders (2.7 ± 0.9 vs. 1.9 ± 0.6; p   Conclusion:  Echocardiographic PVR can differentiate between CRT responders and non-responders. PVR is a better predictor of CRT response than PAP.
Neurology and neurosurgery
Authors: Jothy Kandasamy
Journal: BMJ (2004)

The internet is a good resource for the trainee neurologist or neurosurgeon and there are several helpful websites relating to aspects of fundamental neuroscience, clinical practice, and research.

A good website to start with is www.neuropat.dote.hu. This site is run by the Department of Neurology, University of Debrecen, Hungary, and geared towards education. It provides links to comprehensive information on basic neuroanatomy, neurophysiology, neuropathology, clinical examination, and investigation. Also indexed are tutorials, self-examinations, historical advances, journals, case …
SAFETY OF RHYTHM CONTROL AND CARDIOVERSION FOR PATIENTS WITH RECURRENT SYMPTOMATIC ATRIAL FIBRILLATION IN THE ABSENCE OF ANTICOAGULATION FOLLOWING PERCUTANEOUS LEFT ATRIAL APPENDAGE OCCLUSION
Authors: Rajan Shah, Waleed Al-Darzi, Adam Greenbaum, Marvin Eng, Dee Dee Wang, Joshua Greenberg, Marc Lahiri, Arfaat Khan, William W. O’Neill, Claudio Schuger, Gurjit Singh
Journal: Journal of the American College of Cardiology (2018)
I'm in F1 and pregnant—what do I do now?
Authors: Sarah Thomas
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
External beam radiotherapy (EBRT) and high dose rate (HDR) brachytherapy for intermediate and high-risk prostate cancer: Whole pelvis or prostate-only EBRT?
Authors: Hannah Tharmalingam, Yatman Tsang, Ananya Choudhury, Peter Hoskin
Journal: Journal of Clinical Oncology (2018)

86 Background: In high-risk prostate cancer, the risk of occult lymph node metastases in the pelvic lymph nodes can be as high as 40%. However, the use of whole pelvis radiotherapy (WPRT) in high-risk patients remains controversial with mixed retrospective evidence and two negative prospective trials. Data from a national UK database of patients treated with external-beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy was reviewed to evaluate the benefit of pelvic treatment. Methods: From 2009 to 2013, 755 patients with intermediate- and high-risk prostate cancer (clinical stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen (pPSA) ≥10) were treated with EBRT and HDR brachytherapy. The pelvic nodes to the level of the common iliac chain were treated in 370 patients with a dose of 46Gy in 23 fractions. The remaining 385 patients received radiotherapy to the prostate only (PORT) at a dose of 37.5Gy in 15 fractions. A single dose of 15Gy was delivered with HDR brachytherapy in each case. Corresponding biologic effective doses to the prostate were 107Gy and 100Gy respectively (α/β = 1.5). 96.5% of patients received ADT with a median duration of 24 months. Biochemical failure was defined as a PSA rise of ≥2ng/ml above nadir. Analysis used log-rank and Cox univariate and multivariate tests. Results: Median follow-up was 4.5 years; 5-year biochemical progression-free survival rates for the WPRT versus the PORT arms were 88% vs 80% (p &lt; 0.05) for all patients and 89% vs 76% (p &lt; 0.05) for high-risk patients. Differences in bPFS remained significant (p &lt; 0.05) after accounting for Gleason score, pPSA, T stage and ADT duration as co-variates. There was no difference in overall survival. Conclusions: Whole pelvis EBRT with HDR brachytherapy appears to significantly improves 5-year biochemical progression-free survival in intermediate- and high-risk prostate cancer compared to prostate-only EBRT and HDR brachytherapy which persists after allowing for covariates including presenting tumour parameters and ADT use. The PIVOTAL boost trial in the UK will assess this further in a prospective randomised study.
Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML
Authors: Matteo Zampini, Claudia Tregnago, Valeria Bisio, Luca Simula, Giulia Borella, Elena Manara, Carlo Zanon, Francesca Zonta, Valentina Serafin, Benedetta Accordi, Silvia Campello, Barbara Buldini, Andrea Pession, Franco Locatelli, Giuseppe Basso, Martina Pigazzi
Journal: Leukemia (2018)
LDL TRIGLYCERIDES AND CORONARY ARTERY DISEASE: AN EPIDEMIOLOGICAL AND GENETIC STUDY
Authors: Günther Silbernagel, Hubert Scharnagl, Marcus Kleber, Graciela Delgado, Tatjana Stojakovic, Reijo Laaksonen, Ulf Landmesser, Jeanette Erdmann, Heribert Schunkert, Winfried März, Tanja Grammer
Journal: Journal of the American College of Cardiology (2018)
COMPARATIVE CARDIOVASCULAR SAFETY AND EFFECTIVENESS OF LINAGLIPTIN IN ROUTINE CARE: AN INTERIM ANALYSIS FROM A MONITORING PROGRAM
Authors: Elisabetta Patorno, Chandrasekar Gopalakrishnan, Dorothee B. Bartels, Kimberly G. Brodovicz, Andrea Meyers, Julie Barberio, Jun Liu, Sebastian Schneeweiss
Journal: Journal of the American College of Cardiology (2018)
Independent imaging review (IIR) results in a phase 3 trial of lenvatinib (LEN) versus sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC).
Authors: Riccardo Lencioni, Masatoshi Kudo, Richard S. Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Ann-Lii Cheng, Fabio Piscaglia, Guohong Han, Masafumi Ikeda, Krzysztof Simon, Dmitry Komov, Xuenong OuYang, T.R. Jeffry Evans, Max W. Sung, Terri A. Binder, Andrew Damon, Silvija Kraljevic, Min Ren, Baek-Yeol Ryoo
Journal: Journal of Clinical Oncology (2018)

345 Background: LEN showed treatment effect on OS by statistical demonstration of noninferiority to SOR in a phase 3 study in pts with uHCC, with significant improvement ( P &lt; 0.00001) in median PFS (7.4 vs 3.7 mos; HR: 0.66; 95% CI, 0.57−0.77), median TTP (8.9 vs 3.7 mos; HR: 0.63. 95% CI, 0.53−0.73), and ORR (24% vs 9%). Tumor assessments were by investigator review (IR) per modified RECIST (mRECIST). We present IIR results to assess concordance for IR vs IIR and mRECIST vs RECIST 1.1 by IIR. Methods: In this open-label study, pts with uHCC, ≥ 1 measurable target lesion, BCLC stage B or C, Child-Pugh class A, ECOG PS ≤ 1, and no prior systemic therapy were randomized 1:1 to LEN (body weight ≥60 kg: 12 mg/d; &lt;60 kg: 8 mg/d) or SOR 400 mg twice daily. Primary endpoint was OS. Secondary efficacy endpoints were PFS, TTP, and ORR by mRECIST. IR tumor assessments were done every 8 wks. Post hoc exploratory blinded IIR studies were done using mRECIST and RECIST 1.1 (first timepoint at wk 8). Results: A total of 954 pts enrolled (LEN: 478; SOR: 476), of which 952 (99.8%) pts were IIR assessable (table). Adjudication rate (AR; percentage of cases adjudicated due to disagreement) for timepoint of PD was similar for mRECIST (47%) and RECIST 1.1 (45%); for responder (CR or PR)/nonresponder (SD, PD, or not evaluable [NE]), it was 32% for mRECIST and 17% for RECIST 1.1. PFS and TTP results were nearly the same per mRECIST by IIR as by IR and the same by IIR per mRECIST and RECIST 1.1. Very good concordance was seen between IIR and IR in best overall response (BOR) per mRECIST with the greatest discordance due to more pts being assessed as PR than SD for LEN. Conclusions: IIR supports IR results. ORR was higher in both arms by IIR vs IR but relative ORR was preserved in LEN vs SOR. Higher AR for IIR per mRECIST on response may be due to the greater number of responders or disease complexity. Median PFS and TTP were the same by IIR per mRECIST and RECIST 1.1, showing these data can be compared between methods. Clinical trial information: NCT01761266. [Table: see text]
Dual Inhibition of IGF-1R and ErbB3 Enhances the Activity of Gemcitabine and Nab-Paclitaxel in Preclinical Models of Pancreatic Cancer
Authors: Adam J. Camblin, Emily A. Pace, Sharlene Adams, Michael D. Curley, Victoria Rimkunas, Lin Nie, Gege Tan, Troy Bloom, Sergio Iadevaia, Jason Baum, Charlene Minx, Akos Czibere, Chrystal U. Louis, Daryl C. Drummond, Ulrik B. Nielsen, Birgit Schoeberl, J. Marc Pipas, Robert M. Straubinger, Vasileios Askoxylakis, Alexey A. Lugovskoy
Journal: Clinical Cancer Research (2018)

Purpose: Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance. Assessment of IGF-1R inhibitors in combination with standard-of-care chemotherapy, however, failed to demonstrate significant clinical benefit. The aim of this work is to unravel mechanisms of resistance to IGF-1R inhibition in pancreatic cancer and develop novel strategies to improve the activity of standard-of-care therapies.Experimental Design: Growth factor screening in pancreatic cancer cell lines was performed to identify activators of prosurvival PI3K/AKT signaling. The prevalence of activating growth factors and their receptors was assessed in pancreatic cancer patient samples. Effects of a bispecific IGF-1R and ErbB3 targeting antibody on receptor expression, signaling, cancer cell viability and apoptosis, spheroid growth, and in vivo chemotherapy activity in pancreatic cancer xenograft models were determined.Results: Growth factor screening in pancreatic cancer cells revealed insulin-like growth factor 1 (IGF-1) and heregulin (HRG) as the most potent AKT activators. Both growth factors reduced pancreatic cancer cell sensitivity to gemcitabine or paclitaxel in spheroid growth assays. Istiratumab (MM-141), a novel bispecific antibody that blocks IGF-1R and ErbB3, restored the activity of paclitaxel and gemcitabine in the presence of IGF-1 and HRG in vitro Dual IGF-1R/ErbB3 blocking enhanced chemosensitivity through inhibition of AKT phosphorylation and promotion of IGF-1R and ErbB3 degradation. Addition of istiratumab to gemcitabine and nab-paclitaxel improved chemotherapy activity in vivoConclusions: Our findings suggest a critical role for the HRG/ErbB3 axis and support the clinical exploration of dual IGF-1R/ErbB3 blocking in pancreatic cancer. Clin Cancer Res; 24(12); 2873-85. ©2018 AACR.