tbuckley/cabot-search huggingface dataset:
Safety and efficacy of the addition of simvastatin to panitumumab in <i>KRAS</i> mutant metastatic colorectal cancer patients.
Authors: Henk-jan Guchelaar, Jara M Baas, Lisanne Krens, Monique M.E.M. Bos, Johanna Elisabeth A. Portielje, Erdogan Batman, Hans Gelderblom
Journal: Journal of Clinical Oncology (2013)

e14558 Background: Epithelial growth factor receptor (EGFR) inhibitors are not effective in KRAS mutant colorectal tumors. In these tumors the k-ras protein is activated by post-translational modification by binding farnesyl (C15) and geranylgeranyl (C17) moieties. Both are products of the mevalonate pathway, as is cholesterol. Statins (HMG-CoA-reductase inhibitors) not only inhibit synthesis of cholesterol, but also of C15 and C17 and thus may relevantly inhibit post-translational activation of ras proteins. Therefore, statins may inhibit the expression of the mutant KRAS phenotype and normalize the phenotype into KRAS wild type. In a phase II study we investigated whether simvastatin treatment renders KRAS mutant colorectal tumors sensitive to panitumumab. Methods: Major eligibility criteria were advanced or metastatic colorectal cancer failing prior 5FU, oxaliplatin and irinotecan containing regimens, with a mutation in codon 12, 13 or 61 of KRAS gene on tumor sample. Patients were treated with simvastatin 80mg once daily and panitumumab 6mg/kg every 2 weeks. Primary objective was to investigate the percentage of patients free from progression and alive 11 weeks after the first administration of panitumumab. This phase II study was performed in a Simon two stage design, performing an interim analysis after the enrolment of 15 patients. When at least 6 of these patients (i.e. 40%) were to be alive and free from progression free at 11 weeks after the first administration of panitumumab (similar to the results of the KRAS wild type population of the phase III study), another 31 patients would be included during stage 2. Results: Fifteen evaluable patients were enrolled by 4 study sites. Only one patient was free from progression 11 weeks after start of panitumumab treatment (6.7%). Mean progression free survival was 9.1 weeks (range 5-17 weeks). Most frequent reported side effect was skin toxicity (40%), one patient experienced myositis grade 3. Conclusions: Simvastatin 80mg once daily was not able to inhibit the KRAS mutant phenotype sufficiently to reach sensitivity to panitumumab in colorectal cancer patients with a mutation in the KRAS gene. Clinical trial information: NCT01110785.
Compensatory strategies below the behavioural surface in autism: a qualitative study
Authors: Lucy Anne Livingston, Punit Shah, Francesca Happé
Journal: The Lancet Psychiatry (2019)

Little is known about the compensatory profile in autism; that is, people with autism spectrum disorder who show few symptoms in their behavioural presentation, despite continuing to report autism-related cognitive difficulties or differences. Even less is known about the specific compensatory strategies that these individuals use to disguise autism at the behavioural surface, both in the clinic and everyday life. It is also currently unclear whether individuals without a formal autism diagnosis, but experiencing autistic-like difficulties, use similar compensatory strategies, potentially enabling them to sit below the diagnostic threshold. This study aimed to investigate social compensatory strategies, and their effect on diagnosis and clinical outcome, in adults with and without autism.In this study, individuals aged 18 years or older who responded to a study advert that was distributed worldwide via social media and the UK National Autistic Society formed a convenience sample. Participants self-reported their use and experiences of compensatory strategies using an online platform. Novel analyses, including a qualitative thematic approach, were used to interpret their responses and gain insight into compensatory strategies in autism.Between Oct 19, 2017, and Jan 2, 2018, 136 adults (58 had a clinical diagnosis of autism, 19 self-identified but were not formally diagnosed as autistic, and 59 were not diagnosed or self-identified, but nevertheless reported social difficulties) completed the online study questions. The findings suggested that there are multiple compensatory strategies with distinct characteristics, individual and environmental factors that modulate compensatory strategy use and success, positive (social relationships, independence, employment) and negative (poor mental health, late diagnosis) outcomes associated with compensatory strategy use, and that individuals without a diagnosis use compensatory strategies that are qualitatively similar to individuals with a diagnosis.Increased awareness and measurement of compensatory strategy use in autism should guide future diagnostic guidelines, towards improved diagnostic accuracy and support for people with autism spectrum disorder whose cognitive difficulties are not immediately evident in observable behaviour.UK Medical Research Council and UK National Institute for Health Research.
Clinically Significant Fibrosis Is Associated With Longitudinal Increases in Fibrosis-4 and Nonalcoholic Fatty Liver Disease Fibrosis Scores
Authors: Preya Janubhai Patel, Johnson Chieh-Yu Cheng, Xuan Banh, Lucy Gracen, Daniel Radford-Smith, Fabrina Hossain, Leigh Ula Horsfall, Kelly Lee Hayward, Suzanne Williams, Tracey Johnson, Nigel Neil Brown, Nivene Saad, Katherine Anne Stuart, Anthony William Russell, Patricia Casarolli Valery, Andrew Donald Clouston, Katharine Margaret Irvine, Anne Bernard, Elizabeth Ellen Powell
Journal: Clinical Gastroenterology and Hepatology (2019)
Prognostic markers for oropharyngeal cancer after docetaxel, 5-FU, and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy.
Authors: Sang-Hee Cho, Woo Kyun Bae, Hyun-Jeong Shim, Won-young Choi, Jun-Eul Hwang, Yoo-Duk Choi, Sang-Chul Lim, Ik-Joo Chung
Journal: Journal of Clinical Oncology (2013)

e17005 Background: HPV is associated with prognosis of oropharyngeal cancer, and the incidence has been increased in not only western countries, but also Asian. This study aims to assess the prognostic role of HPV expression and clinical factors after induction chemotherapy followed by chemoradiotherapy for locally advanced oropharyngeal cancer in Korean patients. Methods: A retrospective review of 74 patients with known HPV status and treated with the induction chemotherapy of docetaxel, cisplatin and 5-FU followed by chemoradiotherapy was performed. HPV infection was evaluated with in situ hybridization (ISH) for HPV and p16 protein expression. Results: The median age is 65 (range 43-80) years with male 69, female 5. Among them, 36 patients (49%) are current smokers and 17 patients (23%) are heavy drinkers. Nine patients (12%) show HPV positive in ISH and 35 patients (47%) expressed p16 protein. In response analysis, there is an increasing trend of complete response (CR) in p16 positive patients (34.3%) compared with p16 negative patients (17.9%; P=0.055). HPV expression had no significance with CR. Tumor recurrence showed significantly higher in HPV-negative patients (P=0.044) and p16 (P=0.015) than HPV and p16 positive patients, respectively. In survival analysis, even though the median value was not reached until this time, it showed better trend of PFS in p16 positive patients than p16 negative patients (P=0.072). In univariate analysis of HPV status and clinical parameters, the expression of p16 or HPV had no significant association with survival. However, performance status (PS), T staging, tumor response are significant factors associated with PFS. And PS (0 vs. 1-2) showed a strong relation with PFS in multivariate analysis (HR: 0.24, P=0.001) Conclusions: p16 is a prognostic marker for oropharyngeal cancer patients treated with triple induction chemotherapy followed by CRT and it would be a better surrogate marker for HPV infection than HPV ISH. In addition to biomarker, clinical parameter such as PS has been still important factor of treatment outcome in oropharyngeal cancer patients.
Helen Salisbury: “Alexa, can you do my job for me?”
Authors: Helen Salisbury
Journal: BMJ (2019)

I should perhaps be grateful to Matt Hancock, England’s health secretary, for his attempts—no doubt heartfelt—to reduce the workload of GPs. The latest wheeze is for the NHS website to partner up with Amazon.12 When people have a question about their health they can ask Alexa, the virtual assistant in their voice activated speakers, and the reply will be preferentially sourced from the trusted NHS site.

I’m a fan of the NHS website: it’s accurate, up to date, and phrased simply, although key words don’t always land you where …
The gut microbiota influences skeletal muscle mass and function in mice
Authors: Shawon Lahiri, Hyejin Kim, Isabel Garcia-Perez, Musarrat Maisha Reza, Katherine A. Martin, Parag Kundu, Laura M. Cox, Joel Selkrig, Joram M. Posma, Hongbo Zhang, Parasuraman Padmanabhan, Catherine Moret, Balázs Gulyás, Martin J. Blaser, Johan Auwerx, Elaine Holmes, Jeremy Nicholson, Walter Wahli, Sven Pettersson
Journal: Science Translational Medicine (2019)

Transplanting the gut microbiota of pathogen-free mice into germ-free mice improves skeletal muscle mass and strength.
Abstract 13906: Women and ICD: The Influence of Age and Clinical Characteristics on Survival; the Experience of the Italian ClinicalService Multicenter Observational Project
Authors: Stefano Fumagalli, Luigi Padeletti, Niccolò Marchionni, Maurizio Lunati, Alessandro Proclemer, Giuseppe Boriani, Maurizio Landolina, Renato Pietro Ricci, Maurizio Gasparini
Journal: Circulation (2015)

Introduction: The prevalence of heart failure (HF) significantly increases with age especially in women, who are more frequently hospitalized for this condition than men. Despite epidemiological data and the results of some studies showing that implantable cardiac defibrillator (ICD) can be particularly useful in women, undertreatment still represents a significant problem in female gender. Aims of this research were to analyze the age-related characteristics of women who underwent ICD implantation in a large Italian database and to define the predictors of mortality during the follow-up. Methods: In the Italian ClinicalService Multicenter Observational Project, 6311 patients receiving an ICD between 2004 and 2011 were included in 117 centers. Women were 1102 (17.5% of the whole population) and were divided into 3 groups (&lt;65: N=413, 65-74: N=416, ≥75 years: N=273). We evaluated age-related differences in baseline clinical characteristics and, then, we compared survival between women &lt; and ≥75 years during a 27-month follow-up. Results: Age in the three groups was 55±9, 70±3 and 78±3 years, respectively. Coronary artery disease (CAD; 25, 32, 45%), chronic renal failure (CRF; 5, 6, 11%), COPD, diabetes and hypertension steadily grew with age (all p≤0.001). EF was severely reduced in every group (30±12, 28±7 and 30±10, p=0.008), with NYHA III-IV Class more represented among elderly women (52, 58, 62%, p&lt;0.001). Beta-blockers were less often prescribed at advanced age (87, 81, 79%, p=0.022) and CRT-D more often used in subjects ≥65 years (64, 79, 71%, p=0.002). During the follow-up, mortality was significantly higher in older women (5, 7, 12%, p&lt;0.001). Age-group (HR=1.47, p=0.033), CAD (HR=2.98, p&lt;0.001) and the presence of CRF (HR=2.93, p=0.006) were multivariate predictors of prognosis in our group of women with an ICD. CAD (HR=3.45, p&lt;0.001) and CRF (HR=4.14, p=0.004) were independently associated with prognosis also in &lt;75 years patients, while no predictors were found for elderly women. Conclusions: Women presently represent &lt;20% of patients receiving an ICD. Age, CAD and CRF negatively influence survival in this population. However, in older women, traditional risk factors seem to lose their importance.
Evidence vs Consensus in Clinical Practice Guidelines
Authors: Benjamin Djulbegovic, Gordon Guyatt
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Two sources of bias affecting the evaluation of autistic communication
Authors: Pearl Han Li, Melissa Koenig
Journal: Behavioral and Brain Sciences (2019)

Abstract We support Jaswal &amp; Akhtar's interrogation of social motivational accounts of autism and discuss two sources of bias that contribute to how others construe autistic people's communications: (1) an experience-based bias that limits our ability to discern the speaker's action as communicative and (2) a prejudice against the credibility of certain speakers that limits a listener's willingness to believe their testimony.
Comorbid chronic diseases and cancer diagnosis: disease-specific effects and underlying mechanisms
Authors: Cristina Renzi, Aradhna Kaushal, Jon Emery, Willie Hamilton, Richard D. Neal, Bernard Rachet, Greg Rubin, Hardeep Singh, Fiona M. Walter, Niek J. de Wit, Georgios Lyratzopoulos
Journal: Nature Reviews Clinical Oncology (2019)
Factors affecting time to seeking medical advice and start of treatment in breast cancer (BC) patients in Turkey.
Authors: Vahit Ozmen, Sukru Boylu, Engin Ok, Zafer Canturk, Varol Celik, Murat Kapkac, Sadullah Girgin, Mustafa Tireli, Enver Ihtiyar, Orhan Demircan, Mazhar Semih Baskan, Ayhan Koyuncu, Ismet Tasdelen, Esra Dumanli, Fatih Ozdener
Journal: Journal of Clinical Oncology (2013)

e17529 Background: One of the most important reasons of BC mortality is delay in treatment. Due to lack of BC awareness and organized screening programs, total delay time (from first symptoms of BC to initiation of treatment; TDT) is longer in low-middle income countries. The primary goal of this survey was to identify factors affecting TDT in patients with BC. Methods: As a part of previously presented multinational survey, a total of 1.031 BC patients from 12 cities of 5 districts in Turkey were surveyed using a uniform questionnaire. TDT was determined using 8 individual scales, including one pertaining to patient delay and 7 related to subsequent steps in a typical diagnostic process. Regression models were constructed using 17 variables concerning diverse contextual and personal patient characteristics. Time between first symptom and first medical visit (Patient Delay Time; PDT) and time between first medical visit and start of therapy (System Delay Time; SDT) were modeled separately with multilevel regression. Results: Mean PDT, SDT and TDT were 4.8, 10.5 and 13.8 weeks respectively, with 42% of the patients with a delay of &gt;12 weeks. Multilevel regression equation indicated that disregard of discovered symptoms (p&lt;0.001) and having at least secondary level of education (p=0.021) were significantly correlated with longer PDT. Patients with stronger self-examination habits (p=0.009), reporting more support from friends and family (p&lt;0.001) and living in metropolitan areas (&gt;500k) (p=0.006) had shorter PDT. Predictors of longer SDT included disregard (p&lt;0.001) and having a PDT&gt;4 weeks (p&lt;0.001). Shorter SDT was correlated to being older than 60 years of age (p=0.027). Results revealed that diagnosis during periodic check-up or opportunistic mammography vs. symptomatic BC (p&lt;0.001) and having first medical examination by a surgeon resulted in shorter SDT. Conclusions: TDT in Turkey is unacceptably long and system delay accounted for a substantial part of the total delay experienced by breast cancer patients. This points to a need for shortening clinical pathways if possible. A long patient delay calls for research into patient awareness of BC.
Abstract 16812: Clinical Use of Rate Adaptive Pacing With a Leadless Pacemaker: Results From the Micra Transcatheter Pacing System Post-Approval Registry
Authors: Ulrika Birgersdotter-Green, Paul R Roberts, Jonathan P Piccini, Kyoko Soejima, Kurt D Stromberg, Alyssa K Eakley, Mikhael F El-Chami
Journal: Circulation (2018)

Introduction: The Micra transcatheter pacemaker has similar functionality and features to existing transvenous VVIR systems despite its small size and intracardiac location. Rate adaptive pacing with Micra is achieved via a programmable 3-axis accelerometer that detects activity in the presence of cardiac motion and has demonstrated to be proportional to workload in the investigational trial. In this analysis, we report the clinical usage of rate adaptive pacing in the Micra Post-Approval Registry (PAR). Methods: The Micra PAR is a prospective, non-randomized, multi-center registry evaluating safety performance of Micra in real-world clinical practice following commercial release. All patients intended to be implanted with a Micra were eligible for enrollment. Micra PAR patients with device data available from an interrogation at least 30-days post-implant were included in this analysis. The clinical usage of VVIR vs. VVI pacing modes was summarized based upon last device interrogation. Results: Among the 713 patients included in this analysis from 117 centers, average age was 75.4 ± 14.4 years and 60.0% were male. Overall 45.3% had rate adaptive pacing enabled. Of 457 patients with a primary pacing indication of bradyarrhythmia with AF, 58.0% were programmed VVIR (figure). The pacing indication distribution for the VVIR patient group was: 82% bradycardia with AF, 4% sinus node dysfunction, 8% AV block, 4% syncope, and 1% other. Among patients with a primary indication of syncope or sinus node dysfunction, the majority were programmed VVI (83.9% and 79.1%, respectively). Of patients with &lt;10% pacing, 2.5% were programmed VVIR vs. 97.5% VVI. Of those with &gt;90% pacing, 88.8% were VVIR vs. 11.2% VVI. Conclusions: In real-world clinical practice, VVIR was programmed in &lt;50% of Micra patients. Patient groups with the highest utilization of VVIR mode include those with &gt;90% ventricular pacing and those with a primary pacing indication of bradyarrhythmia with AF.
Independent validation of prognostic value of 22 micrornas (miRs) in stage I-II squamous cell lung cancer (SqCLC).
Authors: Marcin Tomasz Skrzypski, Piotr Czapiewski, Wojciech Biernat, Krzysztof Goryca, Lucjan Wyrwicz, Ewa Jassem, Ryszard Pawlowski, Witold Rzyman, Jacek Jassem
Journal: Journal of Clinical Oncology (2012)

10561 Background: About 50% of NSCLC patients (pts) will develop distant metastases following pulmonary resection. Currently, apart from clinical stage at diagnosis, there are no reliable factors to select high risk pts for adjuvant chemotherapy. We previously demonstrated prognostic value of 22 miRs in frozen tissue samples of early stage SqCLC, and the feasibility of their expression assessment in formalin fixed paraffin embedded (FFPE) samples (Skrzypski et. al. J Clin Oncol 2010;28;15s). In this study, we validated the prognostic value of these miRs in an independent cohort of early SqCLC pts. Methods: FFPE tumor samples were obtained from 132 stage I-II SqCLC pts who underwent radical pulmonary resection, 42% of whom developed distant metastases. Median follow-up of pts who did not develop metastases was 5.6 years (range, 4.1-10.0 years). miRs were isolated from tumor tissue with RecoverAll kit (Ambion). Expression of 22 miRs previously found to be related to the risk of metastases was analyzed by RT-PCR assay (Appliedbiosystems). Raw data were normalized vs. the expression of U6. Individual miRs and the risk score comprising 5 most predictive miRs were correlated with distant metastases-free survival (MFS). Results: Eight miRs were significantly relatedtoMFS. MiR-192 was significantly correlated with MFS (p=0,0007; p=0,02 after correction for multiple comparisons). The 5-miR risk score was an independent prognostic factor (p=1.70E-06) in a multivariate analysis comprising stage (p=1,10E-03) and histological grade (p=0,46). Using the median of the risk score as a cut-off value, the median MFS was 1.73 years in the high risk group, and not reached in the low risk group (HR=2.11). The sensitivity and specificity of the risk score to predict the occurrence of distant metastases were 66% and 64%, respectively. Conclusions: Risk score based on expression of 5 miRs is a strong and independent predictor of distant relapse in operable early SqCLC.
Regional Differences in Secondary Prevention Therapy—Geography Should Not Be Destiny
Authors: Ann Marie Navar, Gregg C. Fonarow
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal