tbuckley/cabot-search huggingface dataset:
ACC/AHA guidelines determining statin eligibility better predicted CVD than ATP-III guidelines
Authors: Raul D. Santos
Journal: Annals of Internal Medicine (2015)

Source Citation Pursnani A, Massaro JM, D’Agostino RB Sr, O’Donnell CJ, Hoffmann U. Guideline-based statin eligibility, coronary artery calcification, and cardiovascular events. JAMA. 2015;314:134-41. 26172893
EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice
Authors: A N Colebatch-Bourn, C J Edwards, P Collado, M-A D'Agostino, R Hemke, S Jousse-Joulin, M Maas, A Martini, E Naredo, M Østergaard, M Rooney, N Tzaribachev, M A van Rossum, J Vojinovic, P G Conaghan, C Malattia
Journal: Annals of the Rheumatic Diseases (2015)

To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13 277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion.
Cytokine response in pediatric patients with pandemic H1N1 influenza virus infection and pneumonia: Comparison with pediatric pneumonia without H1N1 infection
Authors: Myung Chul Hyun, Dong Won Lee, Yeo Hyang Kim
Journal: European Respiratory Journal (2011)

Objectives:  We investigated serum cytokine levels in pediatric patients with pandemic H1N1 virus infection-pneumonia and in pediatric patients with pneumonia but without H1N1 infection, and examined correlations between cytokine levels and clinical/laboratory findings.   Methods:  Fifty-seven cases of infection by H1N1 virus were confirmed by RT-PCR and enrolled. Of these 57 cases, 26 had a severe H1N1 infection (group 1), and 31 had a mild H1N1 infection (group 2). Sera from 18 cases with pneumonia without H1N1 infection (group 3) were used as controls. The serum levels of 10 cytokines were determined by multiplex assay.   Results:  The serum levels of IFN-a, IL-6, and IP-10 were significantly higher in H1N1 infected cases than in group 3, and levels of IL-6 and IP-10 were significantly higher in group 1 than in group 2. The level of IL-10 was significantly higher in groups 1 and 3 than in group 2. However, levels of IFN-a, TNF-a, and IL-17 were not significantly different between the three groups. IL-1β, IL-4, and MIP-1a were not detectable in most patients. IP-10 and IL-6 levels were found to show negative correlations with lymphocyte count and oxygen saturation.   Conclusions:  We found higher levels of cytokines (IFN-a, IL-6, IP-10) of innate immunity than those of acquired immunity in pediatric H1N1 infection. Of the cytokines found to be increased in cases with a H1N1 infection, IP-10 and IL-6 were found to be correlated with disease severity (lymphopenia and hypoxia). IP-10 and IL-6 may be important markers in pediatric H1N1 infection.
Characteristics and Outcomes of Patients With Severe Bioprosthetic Aortic Valve Stenosis Undergoing Redo Surgical Aortic Valve Replacement
Authors: Peyman Naji, Brian P. Griffin, Joseph F. Sabik, Kenya Kusunose, Fadi Asfahan, Zoran B. Popovic, L. Leonardo Rodriguez, Bruce W. Lytle, Richard A. Grimm, Lars G. Svensson, Milind Y. Desai
Journal: Circulation (2015)

Background— With improved event-free survival of patients undergoing primary bioprosthetic aortic valve replacement (AVR), reoperation to relieve severe prosthetic aortic stenosis (PAS) is increasing. We sought to (1) identify of the characteristics of patients with severe bioprosthetic PAS undergoing redo AVR, and (2) assess the outcomes of these patients, along with factors associated with adverse outcomes. Methods and Results— We studied 276 patients with severe bioprosthetic PAS (64±16 years, 58% men) who underwent redo-AVR between 2000 and 2012 (excluding mechanical PAS, severe other valve disease, and transcatheter AVR). Society of Thoracic Surgeons score was calculated. Severe PAS was defined as AV area &lt;0.8 cm 2 , mean AV gradient ≥40 mm Hg, or dimensionless index &lt;0.25. A composite outcome of death and congestive heart failure admission was recorded. Mean Society of Thoracic Surgeons score and mean AV gradients were 8±8 and 53±17 mm Hg, whereas 28% had &gt;II+ aortic regurgitation. Only 39% had an isolated redo AVR, the rest were combination surgeries (coronary bypass and/or aortic surgeries). At 4.2±3 years, 64 (23%) patients met the composite end point (48 deaths and 19 congestive heart failure admissions, 2.5% 30-day deaths). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio, 1.35), higher grades of aortic regurgitation (hazard ratio, 1.29), and higher right ventricular systolic pressure (hazard ratio, 1.3) were associated with worse longer-term outcomes (all P &lt;0.01). Conclusions— At an experienced center, in patients with severe bioprosthetic PAS undergoing redo AVR, the majority undergo combination surgeries but have excellent outcomes.
A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer.
Authors: E T Creagan, S J Green, D L Ahmann, J N Ingle, J H Edmonson, R F Marschke
Journal: Journal of Clinical Oncology (1984)

We assessed the efficacy of a regimen consisting of four cycles of cyclophosphamide, Adriamycin (Adria Laboratories, Inc, Columbus, Ohio), cisplatin (CAP) followed by maintenance with cyclophosphamide, 5-fluorouracil, prednisone (CFP) compared with CFP alone in a randomized trial of 86 patients with advanced breast cancer. The objective regression rates were 46% (CFP) and 49% (CAP with CFP) which included complete regression rates of 7% (CFP) and 4% (CAP with CFP). The median time to progression was nine months for CFP and six months for CAP with CFP. Median survival in the CFP group was 18 months v 11 months in the CAP recipients. Due to the therapeutic trend in favor of patients receiving CFP, we terminated the study before achieving our initially projected accrual. We observed over a twofold excess of substantial nausea and vomiting among patients receiving the platinum-based regimen. In our view, the CAP followed by the CFP regimen is a more toxic program that offers no clinically meaningful improvement over CFP to patients with advanced breast cancer.
Roxadustat (FG-4592)
Authors: Anatole Besarab, Elena Chernyavskaya, Igor Motylev, Evgeny Shutov, Lalathaksha M. Kumbar, Konstantin Gurevich, Daniel Tak Mao Chan, Robert Leong, Lona Poole, Ming Zhong, Khalil G. Saikali, Marietta Franco, Stefan Hemmerich, Kin-Hung Peony Yu, Thomas B. Neff
Journal: Journal of the American Society of Nephrology (2015)

Safety concerns with erythropoietin analogues and intravenous (IV) iron for treatment of anemia in CKD necessitate development of safer therapies. Roxadustat (FG-4592) is an orally bioavailable hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. We performed an open-label, randomized hemoglobin (Hb) correction study in anemic (Hb≤10.0 g/dl) patients incident to hemodialysis (HD) or peritoneal dialysis (PD). Sixty patients received no iron, oral iron, or IV iron while treated with roxadustat for 12 weeks. Mean±SD baseline Hb was 8.3±1.0 g/dl in enrolled patients. Roxadustat at titrated doses increased mean Hb by ≥2.0 g/dl within 7 weeks regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality. Mean±SEM maximal change in Hb from baseline (ΔHb(max)), the primary endpoint, was 3.1±0.2 g/dl over 12 weeks in efficacy-evaluable patients (n=55). In groups receiving oral or IV iron, ΔHb(max) was similar and larger than in the no-iron group. Hb response (increase in Hb of ≥1.0 g/dl from baseline) was achieved in 96% of efficacy-evaluable patients. Mean serum hepcidin decreased significantly 4 weeks into study: by 80% in HD patients receiving no iron (n=22), 52% in HD and PD patients receiving oral iron (n=21), and 41% in HD patients receiving IV iron (n=9). In summary, roxadustat was well tolerated and corrected anemia in incident HD and PD patients, regardless of baseline iron repletion status or C-reactive protein level and with oral or IV iron supplementation; it also reduced serum hepcidin levels.
Feature-based fuzzy connectedness segmentation of ultrasound images with an object completion step
Authors: Sylvia Rueda, Caroline L. Knight, Aris T. Papageorghiou, J. Alison Noble
Journal: Medical Image Analysis (2015)

Medical ultrasound (US) image segmentation and quantification can be challenging due to signal dropouts, missing boundaries, and presence of speckle, which gives images of similar objects quite different appearance. Typically, purely intensity-based methods do not lead to a good segmentation of the structures of interest. Prior work has shown that local phase and feature asymmetry, derived from the monogenic signal, extract structural information from US images. This paper proposes a new US segmentation approach based on the fuzzy connectedness framework. The approach uses local phase and feature asymmetry to define a novel affinity function, which drives the segmentation algorithm, incorporates a shape-based object completion step, and regularises the result by mean curvature flow. To appreciate the accuracy and robustness of the methodology across clinical data of varying appearance and quality, a novel entropy-based quantitative image quality assessment of the different regions of interest is introduced. The new method is applied to 81 US images of the fetal arm acquired at multiple gestational ages, as a means to define a new automated image-based biomarker of fetal nutrition. Quantitative and qualitative evaluation shows that the segmentation method is comparable to manual delineations and robust across image qualities that are typical of clinical practice.
Failure to treat outweigh risk of non-voluntary treatment
Authors: J D Budd
Journal: BMJ (1995)

EDITOR,--Petra Wilson, the legal contributor to the debate on doctors' legal position in treating temporarily incompetent patients, adopts a pessimistic position concerning the legal justification for treating the two patients discussed.1 The intuition of most doctors would suggest that these incompetent patients should be spared the immediate consequences of their disastrous decisions. Fortunately, in Re F the House of Lords confirmed that it was possible for a doctor to give …
MPTP Toxicity: Implications for Research in Parkinson's Disease
Authors: I J Kopin, S P Markey
Journal: Annual Review of Neuroscience (1988)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Neoadjuvant chemotherapy and partial cystectomy for invasive bladder cancer.
Authors: H W Herr, H I Scher
Journal: Journal of Clinical Oncology (1994)

PURPOSE This clinical trial evaluated a bladder-sparing strategy using a combined modality approach of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) chemotherapy followed by a partial cystectomy for patients with invasive (T2-4N0M0) bladder cancer. PATIENTS AND METHODS One hundred eleven surgical candidates received a median of four cycles of neoadjuvant M-VAC. Following treatment, of those with a favorable response to chemotherapy based on cystoscopic examination, 26 underwent a partial cystectomy. RESULTS Of 26 patients, 17 (65%) are alive beyond 5 years (median, 6.9 years; range, 4 to 8), including 14 (54%) with an intact, functioning bladder. Twelve patients (46%) developed bladder recurrences, which were invasive in five (18%) and superficial in seven (26%). Patients with no (P0) or noninvasive (Pis) tumor in their surgical specimens had a 5-year survival rate of 87% (14 of 16), compared with 30% (three of 10) among patients with residual invasive cancer. The majority of deaths was attributed to preexisting metastases. CONCLUSION Neoadjuvant M-VAC chemotherapy permitted bladder-sparing surgery in selected responding patients with invasive bladder neoplasms. The bladder remained at risk for new tumor development, but local recurrences were treated successfully by local therapy or salvage cystectomy.
Pediatric Pulmonary Hypertension
Authors: Steven H. Abman, Georg Hansmann, Stephen L. Archer, D. Dunbar Ivy, Ian Adatia, Wendy K. Chung, Brian D. Hanna, Erika B. Rosenzweig, J. Usha Raj, David Cornfield, Kurt R. Stenmark, Robin Steinhorn, Bernard Thébaud, Jeffrey R. Fineman, Titus Kuehne, Jeffrey A. Feinstein, Mark K. Friedberg, Michael Earing, Robyn J. Barst, Roberta L. Keller, John P. Kinsella, Mary Mullen, Robin Deterding, Thomas Kulik, George Mallory, Tilman Humpl, David L. Wessel
Journal: Circulation (2015)

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.
Abstract 3462: Proteomic profiling reveals novel targets for combination treatment with lanreotide in neuroendocrine tumors
Authors: Omid Fotouhi, Hanna Kjellin, Jamileh Hashemi, Ming Lu, Christofer Juhlin, Anders Höög, Jan Zedenius, Catharina Larsson, Janne Lehtiö, Magnus Kjellman
Journal: Cancer Research (2015)

Abstract Somatostatin analogues (SSAs) are well established in the treatment of neuroendocrine tumors (NETs), including small intestinal NET (SI-NET) due to their tumor growth arrest and symptom relieving characteristics. Here we determined the direct effects of lanreotide treatment on NET cell lines and a primary SI-NET culture. The cell lines HC45 and H727 were treated with a pharmacological concentration of 10 nM lanreotide for different time periods and the proteome, analyzed by in-depth HiRIEF LC-MS/MS, was compared with the proteome of non-treated cells. We quantified 6 451 and 7 801 proteins in HC45 and H727. Differential expression of the candidate proteins APC, BIRC5/survivin, BMPER, C14orf142, FYN, INSM1 and SPAG16 was confirmed by Western blotting. The possible direct anti-proliferative effect of lanreotide was evaluated in the primary SI-NET culture and the HC45, H727 and BON1 cell lines, which showed only a slight inhibition of proliferation. However, based on proteomics driven pathway analysis a significant synergy in anti-proliferative effect of lanreotide was observed when the small molecule IGF1R inhibitor, NVP-AEW541, was combined with lanreotide .This effective combination also represents an indirect model of suppressed IGF1 activity in the NET patients treated with SSA. Targeting of survivin with the small molecule YM155 dramatically reduced the proliferation of HC45. We also studied the effect of lanreotide alone or in combination with IGF-1R inhibitor on signaling pathways PI3K/Akt, Erk1/2 and P38. P38, Erk1/2 and GSK3β phosphorylation was equally increased by lanreotide and/or NVP-AEW541, however, lanreotide-induced AktS473 dephosphorylation was reversed after6 hours, unlike consistent AktS473 dephosphorylation after treating with NVP-AEW451 alone or in combination. In conclusion, we report growth inhibitory and potential feedback pro-growth signaling of the SSA lanreotide on NET cells, highlighting the role of SSAs in modulation of IGF1 in NET cell growth arrest and propose combination treatment candidate targets for improved efficacy of this agent. Citation Format: Omid Fotouhi, Hanna Kjellin, Jamileh Hashemi, Ming Lu, Christofer Juhlin, Anders Höög, Jan Zedenius, Catharina Larsson, Janne Lehtiö, Magnus Kjellman. Proteomic profiling reveals novel targets for combination treatment with lanreotide in neuroendocrine tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3462. doi:10.1158/1538-7445.AM2015-3462
Risk Model–Guided Antiemetic Prophylaxis vs Physician’s Choice in Patients Receiving Chemotherapy for Early-Stage Breast Cancer
Authors: Mark Clemons, Nathaniel Bouganim, Stephanie Smith, Sasha Mazzarello, Lisa Vandermeer, Roanne Segal, Susan Dent, Stan Gertler, Xinni Song, Paul Wheatley-Price, George Dranitsaris
Journal: JAMA Oncology (2015)

Despite multiple patient-centered factors being associated with the risk of chemotherapy-induced nausea and vomiting (CINV), these factors are rarely considered when making antiemetic recommendations.To compare risk model-guided (RMG) antiemetic prophylaxis with physician's choice (PC) in patients receiving chemotherapy for early-stage breast cancer.A randomized clinical trial of 324 patients with early-stage breast cancer undergoing chemotherapy (cyclophosphamide and an anthracycline) for the first time at 2 specialty cancer care centers in Ottawa from April 10, 2012, to September 2, 2014. Patients were randomized to either the RMG arm (n = 154) or the PC control arm (n = 170). Prior to each cycle of chemotherapy patients in the RMG group were categorized as low or high risk for CINV, and their antiemetic treatments were adjusted accordingly.Patients considered to be at low risk received standard dexamethasone and a 5-HT3 antagonist, while those at high risk also received aprepitant with or without olanzapine, based on their risk level. The PC control group received antiemetic agents according to the treating physician's discretion.The primary end points were control of both nausea and vomiting in the acute posttreatment period (first 24 hours after therapy) and in the delayed posttreatment period (days 2-5 after therapy).The total numbers of chemotherapy cycles delivered in the RMG and PC control groups were 497 and 551 respectively. In the acute period, significantly more patients in the RMG group reported no nausea (53.7% [95% CI, 49.2%-58.1%] vs 41.6% [95% CI, 37.4%-45.3%]; P < .001) and no vomiting (91.8% [95% CI, 89.0%-94.0%] vs 82.2% [95% CI, 78.8%-85.3%]; P < .001) compared with the PC control group. Similarly, significantly more patients in the RMG group reported no nausea (39.6% [95% CI, 35.3%-44.1%] vs 30.7% [95% CI, 26.8%-34.7%]; P = .01) and no vomiting (87.1% [95% CI, 83.8%-90.0%) vs 78.0% [95% CI, 74.3%-81.4%]; P < .001) in the delayed period respectively.In this trial, the RMG antiemetic prophylaxis led to improved control of acute and delayed CINV compared with physician's choice of therapy.clinicaltrials.gov Identifier: NCT01913990.
Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial
Authors: Veronica Mulenga, Victor Musiime, Adeodata Kekitiinwa, Adrian D Cook, George Abongomera, Julia Kenny, Chisala Chabala, Grace Mirembe, Alice Asiimwe, Ellen Owen-Powell, David Burger, Helen McIlleron, Nigel Klein, Chifumbe Chintu, Margaret J Thomason, Cissy Kityo, A Sarah Walker, Diana M Gibb
Journal: The Lancet Infectious Diseases (2015)

WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed to compare stavudine, zidovudine, or abacavir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz.In this open-label, parallel-group, randomised trial (CHAPAS-3), we enrolled children from one centre in Zambia and three in Uganda who were previously untreated (ART naive) or on stavudine for more than 2 years with viral load less than 50 copies per mL (ART experienced). Computer-generated randomisation tables were incorporated securely within the database. The primary endpoint was grade 2-4 clinical or grade 3/4 laboratory adverse events. Analysis was intention to treat. This trial is registered with the ISRCTN Registry number, 69078957.Between Nov 8, 2010, and Dec 28, 2011, 480 children were randomised: 156 to stavudine, 159 to zidovudine, and 165 to abacavir. After two were excluded due to randomisation error, 156 children were analysed in the stavudine group, 158 in the zidovudine group, and 164 in the abacavir group, and followed for median 2·3 years (5% lost to follow-up). 365 (76%) were ART naive (median age 2·6 years vs 6·2 years in ART experienced). 917 grade 2-4 clinical or grade 3/4 laboratory adverse events (835 clinical [634 grade 2]; 40 laboratory) occurred in 104 (67%) children on stavudine, 103 (65%) on zidovudine, and 105 (64%), on abacavir (p=0·63; zidovudine vs stavudine: hazard ratio [HR] 0·99 [95% CI 0·75-1·29]; abacavir vs stavudine: HR 0·88 [0·67-1·15]). At 48 weeks, 98 (85%), 81 (80%) and 95 (81%) ART-naive children in the stavudine, zidovudine, and abacavir groups, respectively, had viral load less than 400 copies per mL (p=0·58); most ART-experienced children maintained suppression (p=1·00).All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines.European Developing Countries Clinical Trials Partnership.
Neurosecretion: Beginnings and New Directions in Neuropeptide Research
Authors: Berta Scharrer
Journal: Annual Review of Neuroscience (1987)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More