tbuckley/cabot-search huggingface dataset:
Correlation between depression/anxiety and somatic circulating tumor DNA (ctDNA) alterations in patients with metastatic renal cell carcinoma (mRCC).
Authors: Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Karen L. Clark, Matthew J. Loscalzo, Richard B. Lanman, Kimberly Banks, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

649 Background: A correlation between depression/anxiety and survival has been established in patients (pts) with mRCC (Cohen et al PLoS One 2012). We hypothesize that frequently encountered genomic alterations (GAs) in mRCC may identify pts with these psychological disorders. Methods: Data was obtained from pts with mRCC who received ctDNA profiling as a part of routine clinical care at progression using a CLIAA-certified platform evaluating 73 genes. Genomic alterations (GAs) were pooled for the entire cohort. ICD-9 diagnoses corresponding to anxiety and depression (300 and 311, respectively) were derived from detailed chart review, including review of established diagnoses and medication history. The chi-square test was used to determine the association between frequent GAs (those occurring in ≥5% of the study population) and the presence of depression and anxiety. Results: ctDNA results from 52 pts with mRCC were assessed (gender: 69.2% M, 30.8% F; average age: 58; histology: 84.6% clear cell, 15.4% non-clear cell). The most commonly used 1 st -line treatment was sunitinib (46.1%). GAs were detected in 55.8% of pts. The most frequent GAs in the overall cohort included TP53 (21.1%), VHL (17.3%) and EGFR (7.7%). 5 and 8 pts were coded as having depression and anxiety, respectively. The average number (range) of ctDNA alterations detected was 1.1 (0-4) in patients with depression/anxiety and 1.6 (0-10) in those without (P = 0.001). The presence of VHL mutation was found to occur exclusively in pts with no depression/anxiety (P = 0.05), while 13 patients (25%) lacking VHL GAs had these psychological disorders. Conclusions: The absence of VHL alterations have been associated with poorer survival in pts with RCC (Patard et al Int J Cancer 2008), and our findings suggest that these patients may further have higher rates of depression/anxiety. Our data imply that patients bearing mutations in VHL may a prime target for early psychosocial interventions.
Necessary Clarifications Concerning Results of the SUMMIT Trial
Authors: Katharine Bradley, Emily C. Williams
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
PROFILES OF FRACTIONAL FLOW RESERVE DERIVED FROM COMPUTED TOMOGRAPHY ANGIOGRAPHY (FFRCT) IN PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Elvis Cami, Travis Tagami, Gilbert Raff, Michael Gallagher, Kavitha Chinnaiyan, A. Neil Bilolikar, Austin Fan, Adam Hafeez, Robert Safian
Journal: Journal of the American College of Cardiology (2018)
Junior doctors are treated like factory workers, says royal college head
Authors: Abi Rimmer
Journal: BMJ (2016)

Junior doctors are treated like factory workers, not highly trained professionals, the president of the Royal College of Physicians has said.

Speaking at the Leaders in Healthcare 2016 conference in Liverpool on Wednesday 2 November, Jane Dacre said that junior doctors needed to be given more time for personal development. She said that, to make this possible, the NHS needed to employ more junior doctors.

She said that …
Analysis of over 100,000 patients with cancer for <i>CD274</i> (<i>PD-L1</i>) amplification: Implications for treatment with immune checkpoint blockade.
Authors: Aaron Goodman, David Eric Piccioni, Shumei Kato, Amelie Boichard, Vighnesh Walavalkar, Garrett Michael Frampton, Caitlin Connelly, David Fabrizio, Vincent A. Miller, Jason K. Sicklick, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2018)

47 Background: The majority of patients with Hodgkin lymphoma have copy number alterations in the genes CD274 (PD-L1), PDCD1LG2 ( PD-L2) and JAK2 (chromosome 9p24.1) resulting in high response rates to PD-1/PD-L1 blockade, even in refractory disease. The prevalence and importance of this biomarker as a predictor of response to PD-1 blockade is unknown across all solid tumors. Methods: We analyzed &gt; 100,000 de-identified patient samples from the Foundation Medicine database and 2,039 clinically annotated patients from UCSD. CD274 amplification was called for copy number alterations (CNAs) ≥ 6. PFS was calculated by KM analysis. Results: Altogether, 0.7% of all tumors types had ≥ 6 CNAs in CD274 (Table). CD274 CNAs were identified in 121 tumor histologies. 13 patients at UCSD were found to have CD274 amplification of which nine were treated with PD-1/PD-L1 blockade (either alone or in combination with another immunotherapeutic or targeted therapy) after a median of four prior systemic therapies. The response rate to PD-1/PD-L1 blockade was 67% (6 of 9 patients); median PFS = 15.1 (range, 1.6-21.8+) months (includes 3 objective responses ongoing for 15+ months as well as a glioblastoma with a PR for 4.4+ months). Conclusions: CD274 amplification is rare in most malignancies; however, testing for this alteration is warranted given the frequent and durable responses to PD-1/PD-L1 blockade. [Table: see text]
Association of prostate-specific antigen (PSA) trajectories with risk for metastasis and mortality in non-metastatic castration-resistant prostate cancer (nmCRPC).
Authors: Sophia Li, Zhijie Ding, Jennifer H Lin, Ajay S. Behl, Chris Pericone, Brian Macomson, Neal D. Shore
Journal: Journal of Clinical Oncology (2018)

27 Background: Currently there is insufficient guidance for the management of nmCRPC. This study assessed patient risk of developing metastases and death based on their PSA levels over time. Methods: This was a retrospective study using the Optum electronic health record database (1/1/2007 – 4/30/2016) in men ≥18 years. nmCRPC was defined as a PC diagnosis, 2 rising PSA levels ≥1 week apart, testosterone &lt; 50 ng/dL (post-PC diagnosis), and no ICD-9/10 code or therapy indicating metastasis. Patients were required to have ≥1 PSA record per 3-month period for 9 months following nmCRPC diagnosis. Group Based Trajectory Modeling (GBTM) was used to group patients based on similar PSA trends over 9 months. The association of these PSA groups with metastasis/mortality risk was measured using multivariate Cox proportional hazard regression models. An overall trend for metastasis and mortality across the groups was also tested. Results: From a total of 729 patients included, 4 distinct groups were identified: Group 1 (49% of patients), 2 (32%), 3 (14%) and 4 (5%). Group 1 had the lowest PSA (7 ng/mL) at nmCRPC diagnosis and steady PSA during the 9-month follow-up. In contrast, Groups 2, 3 and 4 had higher PSA at nmCRPC diagnosis (17, 61, 513 ng/mL respectively) and rising PSA during follow-up. There was a trend of increasing metastasis and mortality risk (p &lt; 0.001 for both trends) with the higher PSA groups. For metastasis, Hazard Ratios (HRs) and 95% confidence intervals (CIs) were 1.7 (1.3-2.2), 3.5 (2.5-5.0), 1.8 (0.7-4.7) in Groups 2, 3 and 4, respectively, vs. Group 1. For mortality, HRs (95% CIs) were 1.9 (1.4-2.5), 2.6 (1.8-3.7), 4.5 (2.4-8.4) in Groups 2, 3 and 4, respectively, vs. Group 1. Metastasis-free survival (MFS) independently predicted mortality risk. Patients developing metastasis within 1 year had 4.4-fold greater risk for mortality (95% CI = 2.2-8.8) than those who remained MFS at year 3. Conclusions: A large proportion of nmCRPC patients with PSA increases during the follow-up period had significantly increased risk for metastasis and mortality, with MFS predicting mortality risk. Periodic measurement of PSA may better inform management of nmCRPC.
Infographic: The ‘weekend warrior’ physical activity pattern and mortality
Authors: Gary O’Donovan, I-Min Lee, Mark Hamer, Emmanuel Stamatakis
Journal: British Journal of Sports Medicine (2018)

Our study about the ‘weekend warrior’ physical activity pattern and mortality1 was one of the most talked about studies of 2017.2 Here we offer an infographic summarising the results of our study. The English and Spanish versions of the infographic were created in collaboration with Yann Le Meur of YLMSportScience (www.ylmsportscience.com).

Those who choose to do all their exercise on 1 or 2 days of the week have been termed ‘weekend warriors’.3 Data from the Harvard Alumni Health Study suggest that all-cause mortality risk might be lower in weekend warriors than …
Dysbiotic Subgingival Microbial Communities in Periodontally Healthy Patients With Rheumatoid Arthritis
Authors: Isabel Lopez‐Oliva, Akshay D. Paropkari, Shweta Saraswat, Stefan Serban, Zehra Yonel, Praveen Sharma, Paola de Pablo, Karim Raza, Andrew Filer, Iain Chapple, Thomas Dietrich, Melissa M. Grant, Purnima S. Kumar
Journal: Arthritis & Rheumatology (2018)

Objective Studies that demonstrate an association between rheumatoid arthritis ( RA ) and dysbiotic oral microbiomes are often confounded by the presence of extensive periodontitis in these individuals. This study was undertaken to investigate the role of RA in modulating the periodontal microbiome by comparing periodontally healthy individuals with RA to those without RA . Methods Subgingival plaque was collected from periodontally healthy individuals (22 with RA and 19 without RA ), and the 16S gene was sequenced on an Illumina MiSeq platform. Bacterial biodiversity and co‐occurrence patterns were examined using the QIIME and PhyloTo AST pipelines. Results The subgingival microbiomes differed significantly between patients with RA and controls based on both community membership and the abundance of lineages, with 41.9% of the community differing in abundance and 19% in membership. In contrast to the sparse and predominantly congeneric co‐occurrence networks seen in controls, RA patients revealed a highly connected grid containing a large intergeneric hub anchored by known periodontal pathogens. Predictive metagenomic analysis ( PICRUS t) demonstrated that arachidonic acid and ester lipid metabolism pathways might partly explain the robustness of this clustering. As expected from a periodontally healthy cohort, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were not significantly different between groups; however, Cryptobacterium curtum , another organism capable of producing large amounts of citrulline, emerged as a robust discriminant of the microbiome in individuals with RA . Conclusion Our data demonstrate that the oral microbiome in RA is enriched for inflammophilic and citrulline‐producing organisms, which may play a role in the production of autoantigenic citrullinated peptides in RA .
IMPACT OF BASELINE HEMOGLOBIN ON THE INCIDENCE OF BLEEDING AFTER CORONARY INTERVENTION IN THE ELDERLY
Authors: David Marti, Jose Morales Gallardo, Damaris Carballeira Puentes, David Brau Queralt, Andrea Rueda Linares, Ricardo Concepcion Suarez, Rafael Gómez, Edurne Lopez, Jorge Palazuelos, Salvador Álvarez
Journal: Journal of the American College of Cardiology (2018)
CRT Survey II: a European Society of Cardiology survey of cardiac resynchronisation therapy in 11 088 patients—who is doing what to whom and how?
Authors: Kenneth Dickstein, Camilla Normand, Angelo Auricchio, Nigussie Bogale, John G. Cleland, Anselm K. Gitt, Christoph Stellbrink, Stefan D. Anker, Gerasimos Filippatos, Maurizio Gasparini, Gerhard Hindricks, Carina Blomström Lundqvist, Piotr Ponikowski, Frank Ruschitzka, Giovanni Luca Botto, Alan Bulava, Gabor Duray, Carsten Israel, Christophe Leclercq, Peter Margitfalvi, Óscar Cano, Chris Plummer, Nedim Umutay Sarigul, Maciej Sterlinski, Cecilia Linde
Journal: European Journal of Heart Failure (2018)
Disordered Eating Behaviors Are Not Increased by an Intervention to Improve Diet Quality but Are Associated With Poorer Glycemic Control Among Youth With Type 1 Diabetes
Authors: Miriam H. Eisenberg Colman, Virginia M. Quick, Leah M. Lipsky, Katherine W. Dempster, Aiyi Liu, Lori M.B. Laffel, Sanjeev N. Mehta, Tonja R. Nansel
Journal: Diabetes Care (2018)

OBJECTIVE This study examines whether participation in an 18-month behavioral intervention shown previously to improve overall diet quality inadvertently increases disordered eating behaviors (DEBs) in youth with type 1 diabetes and investigates the association of DEB with multiple measures of glycemic control and variability. RESEARCH DESIGN AND METHODS Participants reported DEB and diabetes management at baseline and 6, 12, and 18 months; masked continuous glucose monitoring, HbA1c, and 1,5-anhydroglucitol (1,5-AG) were obtained concurrently. Linear mixed models estimated the intervention effect on DEB, the association of DEB with diabetes adherence and measures of glycemic control and variability, and whether DEB modified glycemic trajectories. RESULTS There was no intervention effect on DEB (P = 0.84). DEB was associated with higher HbA1c (P = 0.001), mean sensor glucose (P = 0.001), and percent sensor glucose values &amp;gt;180 mg/dL (P = &amp;lt;0.001); with lower 1,5-AG (P = 0.01); and with worse diabetes adherence (P = 0.03). DEB was not associated with percent sensor glucose values &amp;lt;70 mg/dL or any measures of glycemic variability. There was a significant DEB × time interaction effect for mean sensor glucose (P = 0.05) and percent sensor glucose values &amp;gt;180 mg/dL (P = 0.04). Participants reporting less DEB had a developmentally expected deterioration in glycemic control throughout the study. Participants reporting more DEB had poor glycemic control at baseline that remained poor throughout the study. CONCLUSIONS Findings show a potential to improve diet quality without increasing DEB and indicate an association of DEB with persistent hyperglycemia but not hypoglycemia or glycemic variability.
3D Imaging and Quantitative Analysis of Vascular Networks: A Comparison of Ultramicroscopy and Micro-Computed Tomography
Authors: Jeremy Epah, Katalin Pálfi, Franziska Luise Dienst, Pedro Felipe Malacarne, Rolf Bremer, Michael Salamon, Sandeep Kumar, Hanjoong Jo, Christoph Schürmann, Ralf Peter Brandes
Journal: Theranostics (2018)

Classic histology is the gold standard for vascular network imaging and analysis. The method however is laborious and prone to artefacts. Here, the suitability of ultramicroscopy (UM) and micro-computed tomography (CT) was studied to establish potential alternatives to histology.The vasculature of murine organs (kidney, heart and atherosclerotic carotid arteries) was visualized using conventional 2D microscopy, 3D light sheet ultramicroscopy (UM) and micro-CT. Moreover, spheroid-based human endothelial cell vessel formation in mice was quantified. Fluorescently labeled Isolectin GS-IB4 A647 was used for in vivo labeling of vasculature for UM analysis, and analyses were performed ex vivo after sample preparation. For CT imaging, animals were perfused postmortem with radiopaque contrast agent.Using UM imaging, 3D vascular network information could be obtained in samples of animals receiving in vivo injection of the fluorescently labeled Isolectin GS-IB4. Resolution was sufficient to measure single endothelial cell integration into capillaries in the spheroid-based matrigel plug assay. Because of the selective staining of the endothelium, imaging of larger vessels yielded less favorable results. Using micro-CT or even nano-CT, imaging of capillaries was impossible due to insufficient X-ray absorption and thus insufficient signal-to-noise ratio. Identification of lumen in murine arteries using micro-CT was in contrast superior to UM.UM and micro-CT are two complementary techniques. Whereas UM is ideal for imaging and especially quantifying capillary networks and arterioles, larger vascular structures are easier and faster to quantify and visualize using micro-CT. 3D information of both techniques is superior to 2D histology. UM and micro-CT together may open a new field of clinical pathology diagnosis.
MET amplification in NSCLC: Correlation with EGFR mutations and gene amplification
Authors: A. Voutsina, Ar. Kalykaki, A. Koutsopoulos, M. Trypaki, E. Stathopoulos, D. Mavroudis, V. Georgoulias
Journal: Cancer Research (2008)

2169    Background:    MET  amplification in NSCLC was correlated with acquired resistance to EGFR TKIs, gefitinib and erlotinib. The aim of this study was to investigate whether  MET  is amplified in NSCLC prior to TKIs therapy and examine the association of  MET  amplification with EGFR copy number, mutation status and responsiveness to TKIs.   Methods:  Amplification levels of  MET  and  EGFR  genes were determined in FFPE tumor DNA of known  EGFR  and  K-RAS  mutation status from 69 patients with advanced NSCLC treated with gefitinib. Quantitative real-time PCR was performed to analyse  MET  (7q31.2)  and  EGFR  (7p12) gene copy numbers relative to a reference, the  TOP3A  (17p12-p11.2) gene. Relative copy numbers of the  EGFR  and  MET  genes were expressed as the ratio of PCR signals obtained for  EGFR  or  MET  and  TOP3A . The cutoff for normal copy numbers was established as the 95% confidence upper limit (mean + 1.96 standard deviations) of EGFR/TOP3A and MET/TOP3A determined in DNA of normal matched tissue from 14 patients respectively.  Results:  Seven (10%) of the 69 primary tumors exhibited increased MET copy number. None of these tumors had an EGFR mutation whereas 3 of them had K-RAS mutation. No significant association was found between MET copy number and TKI-related disease control rate or survival. Among the 7 patients showing MET amplification 2 (28.5%) with EGFR wild type mutation status exhibited progressive disease. EGFR amplification was detected in 5 (7.2%) patients and among them one (20%) showed MET amplification as well. Response rate was not associated with the EGFR amplification. One patient with a Del19 EGFR mutation reached partial response and another one with wild type mutation status achieved stable disease. The patient showing EGFR and MET amplification had not EGFR and K-RAS mutations and exhibited progressive disease.  Conclusions  :  Met amplification is not a common event in NSCLC prior to EGFR TKIs therapy. However the predictive value of chromosome 7 polysomy should be considered with caution.
Single institutional analysis of pancreatic cancer survival trends based on BMI.
Authors: Jeff Wiisanen, Robert R. McWilliams, William R Bamlet
Journal: Journal of Clinical Oncology (2018)

234 Background: Body mass index (BMI) has been reported to determine risk for pancreatic cancer in addition to outcome, as those with higher BMI have decreased survival. Since May 2011, therapy for pancreatic cancer has improved with the addition of FOLFIRINOX. This study looks at overall survival in relation to BMI since the advent of the FOLFIRINOX. Methods: 2,277 patients with pancreatic adenocarcinoma were identified through the Mayo Clinic SPORE pancreatic cancer registry from 2000-14. Usual adult and BMI at time of enrollment were utilized as a binary variable ( &lt; 30, ≥30 kg/m2). These were analyzed for association with survival using Kaplan-Meier curves and Cox proportional hazards regression. Results: For the 2000-11 and 2011-14 groups, stage distribution was 4.4%, 34.7%, 21.6%, 39.2% and 1.2%, 39%, 22.2%, 37.6%, respectively for stage 1-4. Since pancreatic cancer commonly causes weight loss, more patients were in the higher usual adult BMI (34.6%) compared to enrollment (17.1%). For the period 2000-11, 33.8% of patients had a usual adult BMI of 30+ vs 37.8% for the 2011-14 patients. As previously reported, there was a difference in survival by BMI for the period 2000-May 2011, however, this was not seen for the period June 2011-14. Conclusions: Based on this cohort of patients, the previously reported detrimental effect of elevated BMI on survival in pancreatic cancer patients is no longer seen. This corresponds with the time period of improvement in pancreatic cancer treatment with FOLFIRINOX. Further studies should be performed to confirm our findings and to identify the causality of this association. [Table: see text]
DDRB recommends review of consultant pay scale and introduction of a “principal consultant” grade
Authors: Helen Jaques
Journal: BMJ (2012)

Pay for most UK consultants should be limited to the first five points of the current eight point pay scale, and high performing consultants should be moved on to a new “principal consultant” grade, the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) has recommended.

In its analysis of compensation levels and award schemes for consultants working in UK health services, the DDRB has suggested that the pay scale in use in England, Scotland, and Northern Ireland rewards time in service rather than performance and does not provide enough incentive for job growth or development. Similarly, it has …
Anti-VCAM-1 targeted MRI allows earlier detection of brain metastases in a xenograft melanoma mouse model
Authors: Vinton Cheng, Manuel Sarmiento Soto, Alexandr Khrapichev, Francisco Perez-Balderas, Mark Middleton, Nicola Sibson
Journal: Neuro-Oncology (2018)

Malignant melanoma frequently metastasises to the brain, with between 10% to 40% of patients estimated to develop intracranial metastases following diagnosis. Although treatments are available for managing brain metastases, their frequently late stage of detection limits the therapeutic potential. Anti-VCAM-1 antibody conjugated microparticles of iron oxide (VCAM-MPIO) have previously been shown to enable detection of early intracranial disease with a breast cancer model. To demonstrate the utility of VCAM-MPIO in a xenograft melanoma mouse model for detection of brain metastases. 6 immunocompromised female SCID mice (age 8–9 weeks) were injected intracardially with 1x105 cells of the human-derived melanoma cell line, H1_DL2. Animals were imaged 21 days later by magnetic resonance imaging (MRI) with a multi-gradient echo 3D (MGE3D) sequence, following intravenous injection of VCAM-MPIO. Blood-brain barrier (BBB) integrity was confirmed on post-gadolinium T1-weighted images. Control groups consisted of naïve SCID animals imaged with VCAM-MPIO and tumour-inoculated animals imaged with isotype IgG control antibody conjugated MPIO. Animals were perfusion-fixed, and brain sections assessed immunohistochemically for VCAM-MPIO binding and presence of metastases. Despite lack of BBB breakdown, VCAM-MPIO MRI of tumour bearing mice revealed multiple intracerebral hypointensities indicating specific binding of VCAM-MPIO to cerebral vessels. Both presence of intracerebral micrometastases and VCAM-MPIO binding to VCAM-1 positive vessels were confirmed immunohistochemically. Minimal intracerebral hypointensities were observed in the control groups. VCAM-MPIO MRI can detect melanoma micrometastatic disease in the brain before conventional (gadolinium enhanced) MRI techniques. The potential clinical implication of earlier detection is improved treatment response with reduced patient morbidity and mortality.