tbuckley/cabot-search huggingface dataset:
PATIENT SATISFACTION WITH DAY-CASE BRAIN BIOPSY
Authors: Crispin Weidmann, Joy Roach, Paul Grundy
Journal: Neuro-Oncology (2018)

Image-guided biopsy of intrinsic brain tumours is a common neurosurgical procedure. In 2008 we reported the first UK series of day-case craniotomy and biopsy. In 2017 our unit presented a series of 645 biopsies over 10 years, of which 355 were discharged the same day. We now report the results of the first UK patient satisfaction questionnaire of day-case brain biopsy. Consecutive patients undergoing image-guided biopsies were sent questionnaires. All patients received sedation for their procedure and had a CT brain scan 6 hours post operatively before discharge home. Over nine months a total of 60 brain biopsies were carried out. 43 of these were identified as being suitable for day-case surgery and 39/43 were discharged 6 hours postoperatively. The remainder were thought to be unsuitable for day-case surgery. 32 questionnaires were sent out and 26 responses received. 24/26 patients felt involved in the decision making process to undergo a biopsy. Of the operation 8/26 remember nothing, 8/26 most of, and 10/26 remembered little of the procedure. 22/26 patients felt the timing of discharge was acceptable, only one thought they should remain in hospital for longer. All of the patients received adequate discharge information and felt supported once home. Previous articles have demonstrated the safety of day-case image guided brain biopsies yet enhanced recovery programmes remain scarce in neurosurgery. Sustainability and transformation projects for the NHS require services to look at ways of reducing length of stay to reduce unnecessary admissions. Day-case neurosurgery is a practical option with clear significant cost saving implications. In the last 10 -12 years our unit has challenged accepted practice and undertaken day-case and short stay neuro-oncology surgery. This satisfaction survey of day-case brain biopsies demonstrates that it is well tolerated and accepted by patients and imparts confidence to continue this practice.
<i>Notes from the Field:</i> Spatially Associated Coincident and Noncoincident Cases of La Crosse Encephalitis — North Carolina, 2002–2017
Authors: Brian D. Byrd, Carl J. Williams, J. Erin Staples, Kristen L. Burkhalter, Harry M. Savage, Michael S. Doyle
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In August 2017, the North Carolina Department of Public Health (NCDPH) was notified of a suspected La Crosse virus (LACV) encephalitis case in a boy aged 2 years from western North Carolina. The following day, NCDPH was notified that the patientâs brother, aged 11 years, was also ill with symptoms consistent with viral meningoencephalitis. Laboratory testing confirmed that both siblings had evidence of recent LACV infection.
Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial
Authors: Juan Pablo Frias, Michael A Nauck, Joanna Van, Mark E Kutner, Xuewei Cui, Charles Benson, Shweta Urva, Ruth E Gimeno, Zvonko Milicevic, Deborah Robins, Axel Haupt
Journal: The Lancet (2018)
Abstract 18477: Understanding the Causal Relevance of Apo(a) Isoform Size, Lipoprotein (a) and Oxidized Phospholipids in Coronary Heart Disease
Authors: Danish Saleheen, Philip Haycock, Wei Zhao, Asif Rasheed, Adam Taleb, Philippe Frossard, Sotirios Tsimikas, Joseph L Witzum, Santica Marcovina, Daniel J Rader, John Danesh
Journal: Circulation (2016)

Introduction: The lipoprotein(a) (Lp[a]) pathway is implicated in the etiology of coronary heart disease (CHD). We used a genetic approach to disentangle the relevance to CHD of distinct components...
Abstract 21400: Morphological Analysis of Transcranial Doppler Waveforms for Large Vessel Occlusion Diagnosis
Authors: Robert Hamilton, Samuel Thorpe, Corey Thibeault, Leo Martinez, Seth Wilk, Thomas Devlin
Journal: Circulation (2017)

Introduction: Underlying cardiac conditions such as atrial fibrillation (AF) and cardiac procedures such as transcatheter aortic valve replacement (TAVR) and coronary artery bypass grafting (CABG) have been shown to lead to large vessel occlusions (LVO) causing significant mortality and morbidity and improved pre, peri, post procedural methods for diagnosis are needed. Transcranial Doppler (TCD) is a rapid, inexpensive and portable tool for assessment of cerebral blood flow velocity (CBFV) that is used clinically and has been shown to have potential as a diagnostic aid for LVO. The utilization of the morphological information from the TCD waveform has shown to provide additional diagnostic capabilities in many neurological conditions and may improve LVO detection over traditional TCD metrics of mean velocity and pulsatility index. However, traditional TCD techniques suffer from a number of limitations including operator skill level and variability due to depth and location selection. Hypothesis: The morphology of CBFV waveforms measured with TCD enables detection of LVO while relaxing the need for exact insonation depth relative to occlusion location. Methods: Bilateral TCD scans of 17 pts (66.8 ± 15.2 yrs) with confirmed MCA occlusion were performed immediately following CT/CTA. TCD was also performed on 28 healthy out of hospital controls (55.3 ± 9.5 yrs). Waveform morphology was compared between the two groups. Results: Morphological analysis wherein MCA data for each subject was randomly sampled across depths showed median AUC of 96.3% for LVO detection, with median SEN of 88.9% and SPE of 96.3%. Fig. 1 shows an example of TCD waveforms for control and LVO subjects with similar traditional TCD metrics, but different subtle morphological profiles. Conclusion: Morphological analysis demonstrated high diagnostic accuracy additionally without the need for optimal depth selection, which may reduce the requirement of a trained sonographer.
Abstract 14469: Risk Factors for the Development of Heart Failure in Women Without Obstructive Coronary Artery Disease. A Follow Up Study From the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE)
Authors: Parham Zarrini, Sofy Landes, Janet Wei, Galen Cook-Wiens, Ahmed Albadri, Eileen M Handberg, Vera A Bittner, George Sopko, Steven Reis, Sheryl Kelsey, Carl J Pepine, Noel Bairey Merz
Journal: Circulation (2016)

Women with signs and symptoms of ischemia and no obstructive coronary artery disease (CAD)have previously been shown to have an increased risk of heart failure (HF) hospitalization. However, risk p...
Can microsatellite status of colorectal cancer (CRC) be reliably assessed after neoadjuvant therapy?
Authors: Eduardo Vilar Sanchez, William Wu, Gita Bhatia, Amanda Cuddy, Maureen M. Mork, Sarah A. Bannon, Patrick M. Lynch, Miguel A. Rodriguez-Bigas, Melissa W. Taggart, Y. Nancy You
Journal: Journal of Clinical Oncology (2013)

1525 Background: Universal testing of resected CRC for Microsatellite Instability (MSI) status has been widely advocated. While PCR-based MSI analysis is the current gold standard test, immunohistochemistry (IHC) of mismatch repair (MMR) proteins is more commonly performed. At present, it remains un-established whether PCR-based MSI analysis remains reliable when performed on post-neoadjuvant treated specimens. Our goal was to examine the effect of neoadjuvant therapy on MSI analysis using both in vitro and clinical data. Methods: MSI analysis was performed using the standard panel of 7 markers. In vitro, MMR deficient (HCT116) and proficient (HCT116+Ch3) isogenic cell lines were exposed to 3 cycles of single agent 5-Fluorouracil, Oxaliplatin and Irinotecan and MSI analysis was tested after each cycle. To evaluate the induction of genomic instability, 3 additional coding microsatellite tracts in ATR, BLM and CHK1 were assessed by fragment analysis. In parallel, clinical data from 238 CRCs that were resected after neoadjuvant chemoradiation (n=191) or chemotherapy (n=47) between 9/2009 and 8/2011 were queried for MSI results. MSI analysis performed on paired pre-treatment and post-treatment resection tissues was compared. Results: No changes in MSI status were detected and there was no increase in genomic instability post-treatment in cell line models. In the clinical setting, pre-neoadjuvant MSI testing was limited by the availability of pre-treatment biopsy tissue. 3 patients found to be MMR proficient based on MSI analysis performed on pre-treatment biopsy remained microsatellite stable when analyzed on post-treatment resection tissue. 7 patients were MMR deficient based on MSI analysis performed on post-treatment resection tissue but most had strong clinical evidence to expect MMR deficiency. Conclusions: Based on both preclinical in vitro and clinical data, results of the MSI analysis does not appear to be affected by neoadjuvant therapy for both MMR proficient and deficient cases. In addition, preclinical results do not suggest that neoadjuvant chemoradiation induces an increase in genomic instability. Therefore, MSI analysis remains a reliable gold standard test on post-treatment specimens.
Lack Of Pdgf-B Retention Ameliorates Hypoxia-Induced Pulmonary Hypertension
Authors: P. Tannenberg, E. Folestad, Y. T Chang, H. Gladh, L. Muhl, Bàrbara Laviña, G. Genove, Christer Betsholtz, K. Tran-Lundmark
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
FUNCTIONALLY GUIDED SUPRAMAXIMAL RESECTION OF IDH-WILDTYPE GLIOBLASTOMAS AND THE EFFECT ON PROGRESSION FREE SURVIVAL
Authors: Laurent James Livermore, Sarah Williams, Lei Clifton, Peter McCulloch, Olaf Ansorge, Natalie Voets, Puneet Plaha
Journal: Neuro-Oncology (2018)

Gross total resection (GTR), defined as complete resection of enhancing tumour on post-operative MRI, increases progression free survival (PFS) in patients with glioblastoma. We have extended the concept of functionally guided supramaximal resection (SMR) where the aim of surgery is to resect up to 2 cm beyond the enhancing tumour in all directions, limited only by functional boundaries. Boundaries are identified by pre-operative diffusion tensor imaging (DTI) scans, to estimate white matter fibre tract location, and awake craniotomy with cortical and subcortical stimulation. Prospective non-randomised functionally guided surgical resection was undertaken in all IDH-wildtype glioblastomas undergoing primary surgical resection by the senior author between 2012–2017. Based on post-operative MRI scans, data on extent of tumour resection were analysed calculating tumour, brain and post resection volumes. Patients were then categorised into three different extent of resection groups: subtotal resection (STR), GTR, and SMR. All patients underwent post-operative radiotherapy and chemotherapy as per the Stupp protocol and were followed up with 3-monthly MRI scans. 69 cases of IDH-wildtype glioblastoma underwent resection within the timeframe. Survival data are currently available for 45 cases. The outcome measure is PFS, where progression is defined as recurrence of tumour. For actual treatment received, median PFS was 43.9 months (95% CI, 22.8–89.8 months) in the SMR group, 29.3 months (95% CI, 7.4–72.3 months) in GTR group and 13.3 months (95% CI, 10.3–27.6 months) in the STR group. The Kaplan-Meier survival curves of the three groups are clearly separated with no crossing. The logrank test indicates there is a significant difference (P value = 0.0003) between the survival curves of the three groups. There was no difference in the incidence of post-operative neurological deficit between the three groups. Supramaximal resection provides a significant increase in PFS compared to the current accepted standard of GTR.
Abstract 11426: Combination Therapy with Amlodipine and Atrovastatin Prevents Abdominal Aortic Aneurysm Formation in ApoE-Deficient Mice
Authors: Kikuyo Takahashi, Yasuharu Matsumoto, Kazuki Noda, Zhulanqiqige Do.e, Kimio Satoh, Yoshihiro Fukumoto, Hiroaki Shimokawa
Journal: Circulation (2012)

Background: Recent studies have revealed that both calcium channel blockers (CCBs) and statins exert beneficial effect on various cardiovascular diseases. However, it remains unknown whether CCBs, statins, and their combination therapy prevent formation of abdominal aortic aneurysm (AAA), which is an emerging problem in the aging society. In this study, we thus addressed this important issue in mice. Methods and Results: Six-month-old apolipoprotein E-deficient (ApoE-/-) mice were infused with angiotensin II (AngII, 2500 ng/kg/min) for 1 month (n=64). They were randomly divided into the following 5 groups; group 1 with saline infusion alone (sham); group 2, AngII infusion alone (AngII); group 3 AngII infusion plus amlodipine (1 mg/kg/day, AM); group 4, AngII infusion plus atorvastatin (10 mg/kg/day, AT); and group 5, AngII infusion plus combination therapy with amlodipine (1 mg/kg/day) and atorvastatin (10 mg/kg/day) (Com). There was no difference in blood pressure among the 4 AngII-infusion groups. The c...
Abstract 15206: Sustained Beneficial Effects of Multi-Electrode Renal Sympathetic Denervation on Cardiac Adaptations in Resistant Hypertension: A 24-months Follow-Up Study
Authors: Kyriakos Dimitriadis, Costas Tsioufis, Alexandros Kasiakogias, Panayiotis Vasileiou, Aggelos Papanikolaou, Voula Pylarinou, Elizabeth Lau, Stephen G Worthley, Vasilios Papademetriou, Dimitrios Tousoulis
Journal: Circulation (2015)

Introduction: The favorable impact of renal sympathetic denervation (RDN) on cardiac parameters such as on left ventricular (LV) morphology, geometry and function has been shown up to 6 months after the procedure using diverse ablation systems. Hypothesis: Multi-electrode catheter-based renal sympathetic RDN may have favorable effects on LV structural and functional indices in patients with resistant hypertension after a follow-up of 24 months. Methods: Twenty patients with resistant hypertension [age: 57±10 years, 13 males, office blood pressure (BP): 182/97±19/18 mmHg under 4.5±0.6 drugs] who underwent RDN were followed-up for 24 months. A full transthoracic echocardiographic study was performed in all patients and LV mass was calculated using the Devereux formula and was indexed for body surface area and height. Results: Average office BP was reduced to 148±21/85±14 mmHg at 12 months and to 143±23/80±14 mmHg at 24 months (p&lt;0.001 for all). In the RDN group, LV mass index was significantly reduced from 136±20.1 g/m 2 (56.5±8.7 g/m 2.7 ) to 121±16.6 g/m 2 (50.6±6 g/m 2.7 ) at 12 months and to 115.6±23.3 g/m 2 (48.8±9.3 g/m 2.7 ) at 24 months (p&lt;0.01 for all). RDN decreased mean interventricular septum thickness from 12.1±1.2 mm to 11.4±0.9 mm at 12 months and to 11.3±0.9 mm at 24 months (p&lt;0.05 for all). After RDN, the number of patients with concentric LV hypertrophy (i.e. relative wall thickness &gt;0.42 and LV mass &gt;48 g/m 2.7 for male and &gt;44 g/m 2.7 for female) decreased from 16 patients (80%) at baseline to 10 patients (50%) at 12 months, and to 7 patients (36.8%) at 24 months. Regarding diastolic function RDN caused an increase in mitral valve E'/A' ratio from 0.62±0.28 to 0.70±0.25 at 12 months and to 0.84±0.32 at 24 months (p&lt;0.05 for all) and a decrease in the E/E' ratio from 14.8±6.1 to 11.8±3.7 at 12 months and to 9.7±4 at 24 months (p&lt;0.05 for all). Conclusions: This the first study to show that multi-electrode RDN results in a significant and sustained improvement of diastolic function and attenuation of LV mass index in increased cardiovascular risk resistant hypertensive patients after a follow-up of 24 months. These results suggest long-term pleiotropic cardiovascular benefits of RDN therapy in the setting of resistant hypertension.
Abstract 14916: Regular Practice is an Effective Way to Improve Neonatal Resuscitation Performance Under Stress
Authors: Chenguang Xu, Hongmei Huang, Jiang-Qin Liu, Joseph Y Ting, Rosanna Wong, Winnie Lee, Yin Xue, Georg Schmolzer, Po-Yin Cheung
Journal: Circulation (2017)

Background: NRP® guidelines suggested that simulation should become a standard component in neonatal resuscitation training and should occur more frequently than the current 2-year interval. It is ...
Computational fluid dynamics with imaging of cleared tissue and of in vivo perfusion predicts drug uptake and treatment responses in tumours
Authors: Angela d’Esposito, Paul W. Sweeney, Morium Ali, Magdy Saleh, Rajiv Ramasawmy, Thomas A. Roberts, Giulia Agliardi, Adrien Desjardins, Mark F. Lythgoe, R. Barbara Pedley, Rebecca Shipley, Simon Walker-Samuel
Journal: Nature Biomedical Engineering (2018)
Determinants of Risk for Childhood Obesity
Authors: Michael Freemark
Journal: New England Journal of Medicine (2018)

The body-fat content of a healthy full-term infant rises sharply from 10 to 14% at birth to 25 to 30% at 6 months of age,1 with a consequent 30% increase in the body-mass index (BMI). The accrual of body fat during infancy correlates with, and may be required for, normal linear growth, brain development, and cognitive function.2 After peaking at 6 to 12 months of age, the BMI normally declines to a nadir at 5 to 6 years of age and then "rebounds," rising progressively throughout late childhood and adolescence. Numerous studies have shown that an early or exaggerated "adiposity . . .
Elevated serum ras levels in patients with hematologic malignancies
Authors: Erin M. Nelli, Kim Leitzel, Suhail M. Ali, Hamid A. Al-Mondhiry, Laurence Demers, Walter P. Carney, Peter Hamer, Allan Lipton
Journal: Cancer Research (2006)

1144  Background: Ras is a GDP/GTP binding G protein that acts as a molecular switch converting signals from the cell membrane to the nucleus to regulate cell proliferation, differentiation, and protein synthesis. Activation of ras oncogenes has been identified in a variety of cancers, including 30% of acute myelogenous leukemia (AML) patients. The purpose of our study was to evaluate serum ras levels in hematologic cancer patients. Methods: A novel ras p21 ELISA (Oncogene Science/Bayer Diagnostics) employing two monoclonal antibodies was utilized to quantify ras levels in serum obtained from patients with various hematologic malignancies including AML, acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and chronic lymphocytic leukemia (CLL). A control group of 48 healthy subjects was also used to establish a cutoff for the upper limit of normal for serum ras levels. Fisher’s exact test was used to evaluate differences in the frequency of elevated serum ras levels in control vs. patient groups. Results: The median serum ras level in the 48 healthy control subjects was 125 ng/ml, with a 5% to 95% range of 50-422 ng/ml. The upper limit of normal for serum ras was defined as 422 ng/ml, as determined using the 95th percentile method. Patients were compared to controls. In the total leukemia patient group, 16 of 52 patients (30.8 %) had elevated serum ras levels (p= 0.001). In patient subgroups, 6/24 (25%, p= 0.014) AML patients, 3/7 (42.9%, p= 0.012) ALL patients, and 6 /13 (46%, p= 0.001) CML patients had significantly elevated serum ras levels. Only 1/8 (12.5 %, p= 0.376) CLL patients had an elevated serum ras level. Conclusions: The results of this study indicate that leukemia patients have significantly elevated serum ras levels when compared to healthy controls. Serum ras should be evaluated as a potential biomarker in larger leukemia trials, especially for response to treatment with inhibitors of the ras signaling pathway.
Robust Activity of Avapritinib, Potent and Highly Selective Inhibitor of Mutated KIT, in Patient-derived Xenograft Models of Gastrointestinal Stromal Tumors
Authors: Yemarshet K. Gebreyohannes, Agnieszka Wozniak, Madalina-Elena Zhai, Jasmien Wellens, Jasmien Cornillie, Ulla Vanleeuw, Erica Evans, Alexandra K. Gardino, Christoph Lengauer, Maria Debiec-Rychter, Raf Sciot, Patrick Schöffski
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Gastrointestinal stromal tumors (GIST) are commonly treated with tyrosine kinase inhibitors (TKI). The majority of patients with advanced GIST ultimately become resistant to TKI due to acquisition of secondary KIT mutations, whereas primary resistance is mainly caused by PDGFRA p.D842V mutation. We tested the activity of avapritinib, a potent and highly selective inhibitor of mutated KIT and PDGFRA, in three patient-derived xenograft (PDX) GIST models carrying different KIT mutations, with differential sensitivity to standard TKI. Experimental Design: NMRI nu/nu mice (n = 93) were transplanted with human GIST xenografts with KIT exon 11+17 (UZLX-GIST9KIT 11+17), exon 11 (UZLX-GIST3KIT 11), or exon 9 (UZLX-GIST2BKIT9) mutations, respectively. We compared avapritinib (10 and 30 mg/kg/once daily) versus vehicle, imatinib (50 mg/kg/bid) or regorafenib (30 mg/kg/once daily; UZLX-GIST9KIT11+17); avapritinib (10, 30, 100 mg/kg/once daily) versus vehicle or imatinib [UZLX-GIST3KIT11]; and avapritinib (10, 30, 60 mg/kg/once daily) versus vehicle, imatinib (50, 100 mg/kg/twice daily), or sunitinib (40 mg/kg/once daily; UZLX-GIST2BKIT9). Results: In all models, avapritinib resulted in reduction of tumor volume, significant inhibition of proliferation, and reduced KIT signaling. In two models, avapritinib led to remarkable histologic responses, increase in apoptosis, and inhibition of MAPK-phosphorylation. Avapritinib showed superior (UZLX-GIST9KIT 11+17 and -GIST2BKIT 9) or equal (UZLX-GIST3KIT 11) antitumor activity to the standard dose of imatinib. In UZLX-GIST9KIT 11+17, the antitumor effects of avapritinib were significantly better than with imatinib or regorafenib. Conclusions: Avapritinib has significant antitumor activity in GIST PDX models characterized by different KIT mutations and sensitivity to established TKI. These data provide strong support for the ongoing clinical trials with avapritinib in patients with GIST (NCT02508532, NCT03465722).
A synthesis approach of mouse studies to identify genes and proteins in arterial thrombosis and bleeding
Authors: Constance C. F. M. J. Baaten, Stuart Meacham, Susanne M. de Witt, Marion A. H. Feijge, David J. Adams, Jan-Willem N. Akkerman, Judith M. E. M. Cosemans, Luigi Grassi, Steve Jupe, Myrto Kostadima, Nadine J. A. Mattheij, Martin H. Prins, Ramiro Ramirez-Solis, Oliver Soehnlein, Frauke Swieringa, Christian Weber, Jacqueline K. White, Willem H. Ouwehand, Johan W. M. Heemskerk
Journal: Blood (2018)
The Origin of a New Sex Chromosome by Introgression between Two Stickleback Fishes
Authors: Groves Dixon, Jun Kitano, Mark Kirkpatrick
Journal: Molecular Biology and Evolution (2018)

Introgression is increasingly recognized as a source of genetic diversity that fuels adaptation. Its role in the evolution of sex chromosomes, however, is not well known. Here, we confirm the hypothesis that the Y chromosome in the ninespine stickleback, Pungitius pungitius, was established by introgression from the Amur stickleback, P. sinensis. Using whole genome resequencing, we identified a large region of Chr 12 in P. pungitius that is diverged between males and females. Within but not outside of this region, several lines of evidence show that the Y chromosome of P. pungitius shares a most recent common ancestor not with the X chromosome, but with the homologous chromosome in P. sinensis. Accumulation of repetitive elements and gene expression changes on the new Y are consistent with a young sex chromosome in early stages of degeneration, but other hallmarks of Y chromosomes have not yet appeared. Our findings indicate that porous species boundaries can trigger rapid sex chromosome evolution.