tbuckley/cabot-search huggingface dataset:
PSMA Ligand PET/MRI for Primary Prostate Cancer: Staging Performance and Clinical Impact
Authors: Bernhard Grubmüller, Pascal Baltzer, Sabrina Hartenbach, David D’Andrea, Thomas H. Helbich, Alexander R. Haug, Gregor M. Goldner, Wolfgang Wadsak, Sarah Pfaff, Markus Mitterhauser, Theresa Balber, Neydher Berroteran-Infante, Marko Grahovac, John Babich, Christian Seitz, Gero Kramer, Martin Susani, Peter Mazal, Lukas Kenner, Shahrokh F. Shariat, Marcus Hacker, Markus Hartenbach
Journal: Clinical Cancer Research (2018)

Primary staging of prostate cancer relies on modalities, which are limited. We evaluate simultaneous [68Ga]Ga-PSMA-11 PET (PSMA-PET)/MRI as a new diagnostic method for primary tumor-node-metastasis staging compared with histology and its impact on therapeutic decisions.We investigated 122 patients with PSMA-PET/MRI prior to planned radical prostatectomy (RP). Primary endpoint was the accuracy of PSMA-PET/MRI in tumor staging as compared with staging-relevant histology. In addition, a multidisciplinary team reassessed the initial therapeutic approach to evaluate its impact on the therapeutic management.PSMA-PET/MRI correctly identified prostate cancer in 119 of 122 patients (97.5%). Eighty-one patients were treated with RP and pelvic lymphadenectomy. The accuracy for T staging was 82.5% [95% confidence interval (CI), 73-90; P < 0.001], for T2 stage was 85% (95% CI, 71-94; P < 0.001), for T3a stage was 79% (95% CI, 43-85; P < 0.001), for T3b stage was 94% (95% CI, 73-100; P < 0.001), and for N1 stage was 93% (95% CI, 84-98; P < 0.001). PSMA-PET/MRI changed the therapeutic strategy in 28.7% of the patients with either the onset of systemic therapy/radiotherapy (n = 16) or active surveillance (n = 19).PSMA-PET/MRI can provide an accurate staging of newly diagnosed prostate cancer. In addition, treatment strategies were changed in almost a third of the patients due to the information of this hybrid imaging technique.
Abstract 20210: Optical Coherence Tomography Provides Insight Into Early Coronary Changes Related to Cardiac Allograft Vasculopathy in Pediatric Transplant Recipients
Authors: Kevin C Harris, Stephan Schubert, Enrique Balbacid, Christine Voss, Nolan Lee, Martin C Hosking
Journal: Circulation (2016)

Introduction: Cardiac allograft vasculopathy (CAV) is a common cause of graft failure and mortality in pediatric heart transplant (Tx) recipients. CAV is diagnosed with coronary angiography which i...
ORCA-2: A phase I study of olaparib in addition to cisplatin-based concurrent chemoradiotherapy for patients with high risk locally advanced squamous cell carcinoma of the head and neck.
Authors: Martin David Forster, Ruheena Mendes, Kevin J. Harrington, Teresa Guerrero Urbano, Helen Baines, Victoria J Spanswick, Leah Ensell, John A. Hartley, Sola Adeleke, Paul Gougis, David Leader, Cathy McDowell, Andre Lopes, Jonathan Teague, Sharon Forsyth, Sandy Beare
Journal: Journal of Clinical Oncology (2016)

TPS6108 Background: Standard care for locally advanced squamous cell carcinoma of the head and neck (HNSCC) is cisplatin-based chemoradiotherapy (C-CRT). Use of intensity modulated radiotherapy (IMRT) reduces toxicity to normal tissue but despite aggressive primary management many patients with high risk disease develop recurrence. The PARP-1 inhibitor olaparib inhibits DNA damage repair and may potentiate the anti-tumour activity of C-CRT. Preclinical data demonstrate potent radio-sensitisation but the optimal dosing schedule to enhance anti-tumour activity, whilst allowing normal tissue recovery, has not been investigated clinically. ORCA-2 aims to determine the recommended dose and duration of olaparib to give in combination with weekly cisplatin and IMRT. Methods: This is a phase I trial in which olaparib will be escalated by increasing both the dose (50, 100, 150 & 200 mg bd) and duration (3, 4 & 5 days). Olaparib tablets will be taken orally twice daily (bd) on a weekly dosing schedule (initially 50 mg bd for 3 sequential days), cisplatin 35 mg/m2weekly and IMRT 70 Gy in 35 fractions. Primary endpoint is occurrence of dose limiting toxicities over 13 weeks (7 weeks C-CRT and 6 weeks follow up). A novel dual escalation design called Product of Independent Beta Probabilities Escalation (PIPE) is being used. Escalation decisions are based on a pre-specified maximum allowable target toxicity level of 33%, predicted prior probabilities of toxicity in each dose-duration combination and cumulative toxicity data from a minimum of 2 patients in each cohort. This design allows flexibility and adaptability to provide better estimates of the recommended dose-duration combinations for further investigation than a standard 3+3 escalation. Eligible patients have newly diagnosed, histologically confirmed, high risk, locally advanced HNSCC and WHO performance status 0-1. Blood and fresh tissue will be collected for exploratory biological studies including evaluation of pharmacodynamic markers of PARP inhibition. The trial opened on 28 September 2015 and recruitment is ongoing. Clinical trial information: NCT02308072.
In symptomatic COPD, once-daily triple vs dual therapy reduced moderate or severe exacerbations at 1 year
Authors: Matthew B. Stanbrook
Journal: Annals of Internal Medicine (2018)

ACP Journal Club21 August 2018In symptomatic COPD, once-daily triple vs dual therapy reduced moderate or severe exacerbations at 1 yearMatthew B. Stanbrook, MD, PhDMatthew B. Stanbrook, MD, PhDToronto Western Hospital, University of Toronto, Toronto, Ontario, Canada (M.B.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-169-4-016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLipson DA, Barnhart F, Brealey N, et al; IMPACT Investigators. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378:1671-80. https://pubmed.ncbi.nlm.nih.gov/29668352Clinical Impact RatingsGIM/FP/GP: Pulmonology: References1 Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2018 report). http:\\goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf (accessed 1 Jun 2018). Google Scholar2 Vestbo J, Anderson JA, Brook RD, et al; SUMMIT Investigators. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet. 2016;387:1817-26. [PMID: 27203508] Google Scholar3 Wedzicha JA, Banerji D, Chapman KR, et al; FLAME Investigators. Indacaterol–glycopyrronium versus salmeterol–fluticasone for COPD. N Engl J Med. 2016;374:2222-34. [PMID: 27181606] Google Scholar Author, Article, and Disclosure InformationAffiliations: Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada (M.B.S.)This article was published at Annals.org on 7 August 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 August 2018Volume 169, Issue 4Page: JC16KeywordsChronic obstructive pulmonary diseaseEosinophilsForced expiratory volume in the first second of expirationGlucocorticoid therapyHazard ratioMortalitySafetySerious adverse eventsTreatment guidelines ePublished: 21 August 2018 Issue Published: 21 August 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Clinical spectrum and short-term outcome of adult patients with purpura fulminans: a French multicenter retrospective cohort study
Authors: Damien Contou, Romain Sonneville, Florence Canoui-Poitrine, Gwenhaël Colin, Rémi Coudroy, Frédéric Pène, Jean-Marc Tadié, Martin Cour, Gaëtan Béduneau, Antoine Marchalot, Laurent Guérin, Sébastien Jochmans, Stephan Ehrmann, Nicolas Terzi, Sébastien Préau, François Barbier, Guillaume Schnell, Damien Roux, Olivier Leroy, Claire Pichereau, Elodie Gélisse, Lara Zafrani, Richard Layese, Christian Brun-Buisson, Armand Mekontso Dessap, Nicolas de Prost
Journal: Intensive Care Medicine (2018)
Antibiotics and Acid-Suppressing Medications in Early Life and Allergic Disorders
Authors: Victoria Martin, Corinne Keet, Qian Yuan
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
Abstract 16609: Histological and Molecular Fingerprints of Low-Gradient Aortic Stenosis
Authors: Tudor C Poerner, Daniela Haase, Björn Goebel, Marcus Franz, Gerhard Mall, Hans R Figulla
Journal: Circulation (2013)

Background: Low-gradient aortic stenosis (LGAS) is associated with a worse prognosis and high operative risk compared to aortic stenosis (AS) with normal left ventricular (LV) ejection fraction (EF...
Abstract 12872: The Association of Second Hand Tobacco Smoke With Obstructive and Nonobstructive Atherosclerosis as Assessed by Coronary Computed Tomographic Angiography
Authors: Harvey Hecht, David Yankelevitz, Matthew Cham, Rowena Yip, Jagat Narula, Claudia Henschke
Journal: Circulation (2016)

Introduction: A dose-related association between secondhand tobacco smoke (SHTS) and coronary artery calcium (CAC) has been reported, but the total extent of atherosclerosis has not been investigated. Objective: To assess the relationship of the extent of atherosclerosis on coronary computed tomographic angiography (CTA) to the extent of secondhand tobacco smoke (SHTS) exposure in asymptomatic never smokers. Methods: Two hundred sixty eight never smokers, aged 40-80, completed a risk factor and extent of lifetime SHTS exposure questionnaire providing a total SHTS exposure score. Analyses of the prevalence, extent and plaque characteristics of atherosclerosis on CTA were performed and the independent contribution of SHTS was determined. Results: Coronary atherosclerosis was noted in 48% and was more frequent with low/moderate and high versus minimal SHTS exposure (48% and 69% vs. 25%, P &lt; 0.0001). &gt;50% stenosis, 1-49% stenosis and no stenosis were noted in 6%, 42% and 52% respectively. Adjusted ORs for any atherosclerosis were: 2.1 (95% CI: 1.0-4.4, P=0.05) for low-moderate and 3.5 (95% CI: 1.4-8.5, P=0.01) for high versus minimal SHTS exposure and were not significant for diabetes (P=0.45), hyperlipidemia (P=0.11), hypertension (P=0.65), and renal disease (P=0.24). With increasing SHTS exposure, the number of major vessels (P=0.0013), and the number of segments with any atherosclerosis (p=0.0001) significantly increased as did the number of involved segments with any plaque or stenosis (P &lt; 0.0001), with calcified plaques alone (P &lt;0.0001), with calcified and mixed plaques (P &lt; 0.001) but not noncalcified plaques alone (P = 0.11). Conclusions: The presence and extent of atherosclerosis were associated with the extent of SHTS exposure even when adjusted for other risk factors, further demonstrating the causal relationship of SHTS exposure and coronary disease.
Abstract 13854: Micro-RNA Regulation of Collagen Production by Vascular Smooth Muscle Cells Mediated by La Ribonucleoprotein Domain Family Member 6: Potential Mechanisms Underlying Stable Phenotype of Atherosclerotic Plaque by Insulin-like Growth Factor 1
Authors: Yusuke Higashi, Svitlana Danchuk, Sergiy Sukhanov, Christopher Blackstock, Zhaohui Li, Patricia Snarski, Patrice Delafontaine
Journal: Circulation (2016)

Collagen is a major constituent of the extracellular matrix in atherosclerotic plaques and supports plaque stability. La ribonucleoprotein domain family member 6 (LARP6) is an RNA binding protein, which assists translation of fibrillar collagen, thereby promoting mature collagen deposition. In Apoe-null mice, insulin-like growth factor 1 (IGF1) promoted stable features of plaques by increasing smooth muscle cell (SMC) numbers and mature collagen fibril deposition without increasing plaque burden. To study mechanisms underlying the IGF1’s plaque stabilizing effects, we exposed human aortic SMCs to proatherogenic oxidized LDL (oxLDL) or IGF1 and determined collagen expression levels. OxLDL downregulated collagen (I) by 36.0±3.2% (P&lt;0.05), along with LARP6 (40.9±10.4 % decrease, P&lt;0.05) and procollagen (I) (49.0±8.9 % decrease, P&lt;0.05), which are consistent with decreased translation of procollagen (I) mRNA. IGF1 abolished oxLDL effects, reversing LARP6 and procollagen (I) protein levels, and thus increased collagen (I) to the levels comparable with native LDL-treated control. As we found previously, the IGF1 upregulation of collagen (I) was mediated by enhanced expression of LARP6, however IGF1 did not alter LARP6 mRNA levels, suggesting translational/post-translational mechanisms. Micro RNA regulates translation of mRNAs; in fact, miR-126, miR-744, and miR-1976 target LARP6 mRNA. In human aortic SMCs, oxLDL upregulated miR-1976 by 40.4±0.5 %, implying miR-mediated suppression of LARP6 translation. Intriguingly, IGF1 abrogated the oxLDL upregulation of miR-1976; moreover, IGF1 decreased miR-126 (by 25.0±1.0 %, P&lt;0.05) and miR-744 (by 24.0±0.4 %, P&lt;0.01), further suggesting that downregulation of miRs mediated IGF1 upregulation of LARP6. To evaluate LARP6 expression in human atherosclerotic plaques, atherosclerotic carotid artery sections were stained for LARP6, and it was detected mainly in SMCs in the medial layer and in the plaque fibrous cap, where collagen fibrils are integral components supporting plaque stability. Our findings suggest a novel mechanism of collagen accumulation by miR-dependent LARP6 expression, and provide a basis for a novel therapeutic approach to enhance plaque stability by targeting miR.
Abstract B03: Sequential liquid biopsies reveal dynamic alterations of EGFR driver mutations and indicate EGFR amplification as a new mechanism of resistance to osimertinib in NSCLC
Authors: Franciele Knebel, Fabiana Bettoni, Andrea Shimada, Manoel Cruz, João Victor Alessi, Marcelo Negrão, Luiz Fernando Reis, Artur Katz, Anamaria Camargo
Journal: Clinical Cancer Research (2018)

Abstract Osimertinib is an EGFR-T790M-specific TKI, which has demonstrated impressive response rates in NSCLC, after failure to first-line anti-EGFR TKIs. However, acquired resistance to osimertinib is also observed and the molecular mechanisms of resistance are not yet fully understood. Monitoring and managing NSCLC patients who progressed on osimertinib is, therefore, emerging as an important clinical challenge. Serial liquid biopsies were used to monitor a patient with EGFR-exon19del positive NSCLC, who received erlotinib and progressed through the acquisition of the EGFR-T790M mutation. Erlotinib was discontinued and she received osimertinib. Blood samples were collected at erlotinib progression and during osimertinib treatment for the detection of the activating (EGFR-exon19del) and resistance mutations (EGFR-T790M, EGFR-C797S, BRAF-V600E, METamp and ERBB2amp) in the plasma DNA using digital droplet PCR. Plasma levels of the activating EGFR-exon19del accurately paralleled the clinical and radiologic progression of the disease and allowed early detection of AR to osimertinib. Resistance to osimertinib coincided with the emergence of a small tumor cell subpopulation carrying the known EGFR-C797S resistance mutation and an additional subpopulation carrying amplified copies of EGFR-exon19del. Given the existence of multiple AR mechanism, quantification of the original EGFR activation mutation, instead of the resistance mutations, can be efficiently used to monitor response to osimertinib, allowing early detection of AR. Absolute quantification of both activation and resistance mutations can provide important information on tumor clonal evolution upon progression to osimertinib. Selective amplification of the EGFR-exon19del allele may represent a novel resistance mechanism to osimertinib. Citation Format: Franciele Knebel, Fabiana Bettoni, Andrea Shimada, Manoel Cruz, João Victor Alessi, Marcelo Negrão, Luiz Fernando Reis, Artur Katz, Anamaria Camargo. Sequential liquid biopsies reveal dynamic alterations of EGFR driver mutations and indicate EGFR amplification as a new mechanism of resistance to osimertinib in NSCLC [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B03.
Metabolic syndrome and risk of Parkinson disease: A nationwide cohort study
Authors: Ga Eun Nam, Seon Mee Kim, Kyungdo Han, Nan Hee Kim, Hye Soo Chung, Jin Wook Kim, Byoungduck Han, Sung Jung Cho, Ji Hee Yu, Yong Gyu Park, Kyung Mook Choi
Journal: PLoS Medicine (2018)

The association of metabolic syndrome (MetS) with the development of Parkinson disease (PD) is currently unclear. We sought to determine whether MetS and its components are associated with the risk of incident PD using large-scale cohort data for the whole South Korean population.Health checkup data of 17,163,560 individuals aged ≥40 years provided by the National Health Insurance Service (NHIS) of South Korea between January 1, 2009, and December 31, 2012, were included, and participants were followed up until December 31, 2015. The mean follow-up duration was 5.3 years. The hazard ratio (HR) and 95% confidence interval (CI) of PD were estimated using a Cox proportional hazards model adjusted for potential confounders. We identified 44,205 incident PD cases during follow-up. Individuals with MetS (n = 5,848,508) showed an increased risk of PD development compared with individuals without MetS (n = 11,315,052), even after adjusting for potential confounders including age, sex, smoking, alcohol consumption, physical activity, income, body mass index, estimated glomerular filtration rate, and history of stroke (model 3; HR, 95% CI: 1.24, 1.21-1.27). Each MetS component was positively associated with PD risk (HR, 95% CI: 1.13, 1.10-1.16 for abdominal obesity; 1.13, 1.10-1.15 for hypertriglyceridemia; 1.23, 1.20-1.25 for low high-density lipoprotein cholesterol; 1.05, 1.03-1.08 for high blood pressure; 1.21, 1.18-1.23 for hyperglycemia). PD incidence positively correlated with the number of MetS components (log-rank p < 0.001), and we observed a gradual increase in the HR for incident PD with increasing number of components (p < 0.001). A significant interaction between age and MetS on the risk of incident PD was observed (p for interaction < 0.001), and people aged ≥65 years old with MetS showed the highest HR of incident PD of all subgroups compared to those <65 years old without MetS (reference subgroup). Limitations of this study include the possibilities of misdiagnosis of PD and reverse causality.Our population-based large-scale cohort study suggests that MetS and its components may be risk factors of PD development.
Sixty seconds on . . . getting to know you
Authors: Abi Rimmer
Journal: BMJ (2018)

No, I’m not about to burst into song. But this is about getting to know you, getting to know all about you . . .

A “getting to know you” form introduced by consultants in the paediatric and adult emergency departments of the Royal London Hospital. The forms ask trainees all about themselves, what skills they can bring to the department, and what they want to get out of their training.

The …
Exercise right heart catheterisation before and after pulmonary endarterectomy in patients with chronic thromboembolic disease
Authors: Stefan Guth, Christoph B. Wiedenroth, Andreas Rieth, Manuel J. Richter, Ekkehard Gruenig, Hossein Ardeshir Ghofrani, Matthias Arlt, Christoph Liebetrau, Diethard Prüfer, Andreas Rolf, Christian W. Hamm, Eckhard Mayer
Journal: European Respiratory Journal (2018)

Symptomatic patients with chronic thromboembolic disease (CTED) without pulmonary hypertension often show an excessive increase in mean pulmonary arterial pressure (MPAP) during exercise. We report on the impact of pulmonary endarterectomy (PEA) on pulmonary haemodynamics in a prospective series of 32 consecutive CTED patients who underwent PEA. All patients had a comprehensive diagnostic work-up including right heart catheterisation at baseline and 12 months after PEA. Furthermore, in 12 patients exercise right heart catheterisation was performed before and after PEA. After PEA, MPAP was lower at rest (20±3 versus 17±3 mmHg; p=0.008) and during maximal exercise (39±8 versus 31±6 mmHg; p=0.016). The mean total pulmonary resistance (TPR) decreased from 3.6±0.8 Wood Units (WU) pre-operatively to 2.7±0.7 WU 1 year after PEA (p=0.004) and the mean slope of the MPAP/cardiac output (CO) relationship decreased from 3.6±1.0 to 2.3±0.8 WU (p=0.002). Peak oxygen uptake increased from 1.2±0.4 to 1.5±0.3 L·min −1 (p=0.014) and ventilatory equivalents of carbon dioxide decreased from 39±2 to 30±2 (p=0.002). There was a significant improvement in quality of life assessed by the Cambridge Pulmonary Hypertension Outcome Review questionnaire. In CTED patients, PEA resulted in haemodynamic and clinical improvements. The means of TPR and MPAP/CO slopes decreased to &lt;3.0 WU.
Identifying obstructive sleep apnoea patients responsive to supplemental oxygen therapy
Authors: Scott A. Sands, Bradley A. Edwards, Philip I. Terrill, James P. Butler, Robert L. Owens, Luigi Taranto-Montemurro, Ali Azarbarzin, Melania Marques, Lauren B. Hess, Erik T. Smales, Camila M. de Melo, David P. White, Atul Malhotra, Andrew Wellman
Journal: European Respiratory Journal (2018)

A possible precision-medicine approach to treating obstructive sleep apnoea (OSA) involves targeting ventilatory instability (elevated loop gain) using supplemental inspired oxygen in selected patients. Here we test whether elevated loop gain and three key endophenotypic traits (collapsibility, compensation and arousability), quantified using clinical polysomnography, can predict the effect of supplemental oxygen on OSA severity.36 patients (apnoea-hypopnoea index (AHI) >20 events·h-1) completed two overnight polysomnographic studies (single-blinded randomised-controlled crossover) on supplemental oxygen (40% inspired) versus sham (air). OSA traits were quantified from the air-night polysomnography. Responders were defined by a ≥50% reduction in AHI (supine non-rapid eye movement). Secondary outcomes included blood pressure and self-reported sleep quality.Nine of 36 patients (25%) responded to supplemental oxygen (ΔAHI=72±5%). Elevated loop gain was not a significant univariate predictor of responder/non-responder status (primary analysis). In post hoc analysis, a logistic regression model based on elevated loop gain and other traits (better collapsibility and compensation; cross-validated) had 83% accuracy (89% before cross-validation); predicted responders exhibited an improvement in OSA severity (ΔAHI 59±6% versus 12±7% in predicted non-responders, p=0.0001) plus lowered morning blood pressure and "better" self-reported sleep.Patients whose OSA responds to supplemental oxygen can be identified by measuring their endophenotypic traits using diagnostic polysomnography.