tbuckley/cabot-search huggingface dataset:
Molecular and clinical characterization of BRAF mutations in pancreatic ductal adenocarcinomas (PDACs).
Authors: Michelle Guan, R Joseph Bender, Michael J. Pishvaian, David Charles Halverson, Richard Tuli, Samuel Jacob Klempner, Zev A. Wainberg, Aatur D. Singhi, Emanuel Petricoin, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2018)

214 Background: The activation of the RAS/RAF/MEK/ERK pathway is critical for the proliferation, survival, and tumorigenesis of PDACs. Oncogenic mutations in KRAS (90%) or BRAF (3%) are recurrent genomic alterations, but their co-occurrence is not well described. We reviewed BRAF alterations and clinical outcomes in consecutive PDAC patients (pts). Methods: Perthera, Inc. deploys an IRB-approved registry that was utilized in partnership with PanCAN’s “Know Your Tumor” program. Perthera uses CAP/CLIA accredited multi-Omic profiling, including next generation DNA sequencing (NGS, Foundation Medicine) and proteomics/immunohistochemistry (Neogenomics Inc. and Caris Life Sciences, Inc.). We used a Fisher's exact test with multiple testing correction to compare frequencies of mutations and protein over-/under-expression between BRAF-mutated (n = 21) and BRAF wild type pts (n = 745). Results: Of 766 pancreatic cancer pts, 21 pts were identified with BRAF mutations. 18 pts were diagnosed with PDAC, 1 pancreatoblastoma, 1 pancreatic acinar cell carcinoma, and 1 mixed acinar neuroendocrine carcinoma. Amongst the 18 PDAC pts with BRAF mutations, nine variations were found: V600E (5/18), BRAF fusion (4/18), N486_P490del (3/18), T310I (1/18), K601N (1/18), G596R (1/18), exon 2-10 deletions &amp; S467L (1/18), equivocal amplification of BRAF (1/18), and a BRAF inframe deletion (1/18). KRAS was mutated in 6% of BRAF mutated PDACs, compared to 94% in BRAF wild type PDACs (p &lt; 0.001). Amongst KRAS wild type PDACs, 53% of CDKN2A mutated pts had BRAF mutations vs. only 15% of CDKN2A wild type cases (p &lt; 0.05). Two BRAF mutated pts from the database were given BRAF inhibitors. A sustained response to the combination dabrafenib and trametinib was observed in a BRAF V600E mutated PDAC pt, while no response was seen in a pt with concurrent KRAS G12A &amp; BRAF K601N mutations who received trametinib. Conclusions: BRAF mutations are significantly and inversely correlated with KRAS alterations. The most common BRAF alteration, V600E mutation, was found to be mutually exclusive with the KRAS mutation. Clinical trials targeting BRAF alterations in KRAS wild type pancreatic cancer appears warranted.
Complexity In Primary Care
Authors: Sabina Dosani
Journal: BMJ (2007)

Complexity in Primary Care 

Kieran Sweeney

Radcliffe, 2006

£21.99, 165 pages

ISBN: 1 857 75724 6

Rating:⋆⋆⋆⋆/5



Exeter general practitioner Kieran Sweeney presents an elegant ponderosity: that the explanatory model in contemporary medicine needs to be overhauled to accommodate plurality of world views. This book's strength lies in the way Sweeney analyses thoughts and feelings probably all GPs have grappled with, but never understood. His understanding of the subtleties of what happens between practitioner and patient in consulting rooms is by turns touching, troubling, and thought provoking.

Sweeney graduated in art as well as in …
Cut medical student intake by 2%, government backed report says
Authors: Helen Jaques
Journal: BMJ (2012)

A report commissioned by the government has recommended reducing intake into medical school by 2% in England, starting with the 2013 intake, to improve matching of medical workforce supply and demand from 2025.

Effective planning of medical student numbers would make sure that money was not wasted through training more doctors than the NHS needed, some of whom could be forced to work abroad, said the health minister Dan Poulter.

The Health and Education National Strategic Exchange (HENSE) was commissioned in 2011 to review whether the current levels of medical and dental student intakes were in line with predicted workforce requirements. 

Its baseline forecasts estimated that the …
Quality of life study in patients with unresectable locally advanced or metastatic pancreatic cancer treated with gemcitabine in combination with nab-paclitaxel versus gemcitabine alone:ax-panc-sy001: A phase II randomized study.
Authors: Suayib Yalcin, Faysal Dane, Berna Oksuzoglu, Nuriye Yildirim, Abdurrahman Isikdogan, Metin Ozkan, Guzin Demirag, Hasan Senol Coskun, Bulent Karabulut, Turkkan Evrensel, Mehmet Ali Ustaoglu, Feyyaz Ozdemir, Hande Turna, Tugba Yavuzsen, Faruk Aykan, Alper Sevinc, Hakan Akbulut, Deniz Yuce, Mutlu Hayran, Saadettin Kilickap
Journal: Journal of Clinical Oncology (2018)

346 Background: Although clinical efficacy of gemcitabine in combination with nabpaclitaxel has been shown to be superior to single agent gemcitabine in a randomize phase 3 trial, data are lacking on the quality of life of this combination regimen as first-line therapy in patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma. Methods: We randomly assigned 125 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 to receive gemcitabine, 1000 mg/m2 plus nabpaclitaxel 125 mg/m2 or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Treatment continued until disease progression or unacceptable toxicity. The primary end point was 3-months deterioration-free rate (percentage of patients free from definitive deterioration) and quality of life of patients. Results: The median overall survival was 9.92 months in the gemcitabine plus nabpaclitaxel group as compared with 5.95 months in the gemcitabine group (hazard ratio for death, 0.642, 95% confidence interval, 0.422 to 0.866; p &lt; 0.038). Median progression-free survival was 6.28 months in the combination group and 3.22 months in the gemcitabine group (hazard ratio for disease progression, 0.582; 95% CI, 0.391 to 0.866; p &lt; 0.008). The objective response rate was 37.1% in the combination group versus 23.7% in the gemcitabine group (p &lt; 0.009). Median time to deterioration was 3.68 months in the gemcitabine arm versus 5.36 months in the combination arm. More data on quality of life will be presented. Conclusions: As compared with gemcitabine, gemcitabine plus nabpaclitaxel was associated with an overall and progressive free survival advantage, with increased response rate, without increasing toxicity and deterioration of quality of life. Gemcitabine and nabpaclitaxel combination regimen with this form is a preferable option for the treatment of patients with advanced pancreatic cancer Clinical trial information: EudraCT: 2013-004180-32.
Nil Per Os Before Procedures—Time to Reevaluate the Practice
Authors: Deepak Agrawal
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
RELATIONSHIP BETWEEN HEALTH-RELATED QUALITY OF LIFE AND BLOOD PRESSURE CONTROL IN PATIENTS WITH UNCONTROLLED HYPERTENSION
Authors: Chan Joo Lee, Woo Jung Park, Jung-Won Suh, Eue-Keun Choi, Dong Woon Jeon, Sang-Wook Lim, Dae-Hweok Kim, Kwang Soo Cha, Bong-Ryeol Lee, Nam-Ho Kim, Dongmin Kim, Jong-Won Ha
Journal: Journal of the American College of Cardiology (2018)
Environmental Noise and the Cardiovascular System
Authors: Thomas Münzel, Frank P. Schmidt, Sebastian Steven, Johannes Herzog, Andreas Daiber, Mette Sørensen
Journal: Journal of the American College of Cardiology (2018)

Noise has been found associated with annoyance, stress, sleep disturbance, and impaired cognitive performance. Furthermore, epidemiological studies have found that environmental noise is associated with an increased incidence of arterial hypertension, myocardial infarction, heart failure, and stroke. Observational and translational studies indicate that especially nighttime noise increases levels of stress hormones and vascular oxidative stress, which may lead to endothelial dysfunction and arterial hypertension. Novel experimental studies found aircraft noise to be associated with oxidative stress–induced vascular damage, mediated by activation of the NADPH oxidase, uncoupling of endothelial nitric oxide synthase, and vascular infiltration with inflammatory cells. Transcriptome analysis of aortic tissues from animals exposed to aircraft noise revealed changes in the expression of genes responsible for the regulation of vascular function, vascular remodeling, and cell death. This review focuses on the mechanisms and the epidemiology of noise-induced cardiovascular diseases and provides novel insight into the mechanisms underlying noise-induced vascular damage.
The prognostic impact of neutrophil to lymphocyte ratio in patients with recurrent or metastatic esophageal squamous cell carcinoma receiving immune checkpoint inhibitors.
Authors: Jhe-Cyuan Guo, Chia-Chi Lin, Ta-Chen Huang, Min-Shu Hsieh, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2018)

69 Background: The study explored the prognostic impacts of clinical parameters including neutrophil to lymphocyte ratio (NLR) in recurrent/metastatic esophageal squamous cell carcinoma (R/M ESCC) patients receiving anti-programmed cell death protein-1 (PD-1)/PD ligand 1 (PD-L1)-based therapy. Methods: Thirty-eight patients were enrolled. Tumor response evaluation was made according to Response Evaluation Criteria in Solid Tumours 1.1, and the clinical benefit response (CBR) was defined as complete response, partial response or stable disease at least 6 months. Clinical factors were analyzed for their impacts on patients' overall survival (OS) and progression-free survival (PFS). Formalin-fixed, paraffin-embedded tissues from 8 patients were analyzed by NanoString nCounter Human PanCancer Immune Profiling (NanoString Technologies, Seattle, WA, US). Results: Twenty-six recurrent and 12 de novo metastatic ESCC patients were enrolled. The response rate is 11.8%, and the CBR rate was 21.1%. The median PFS and OS are 2.7 and 5.5 months, respectively. The CBR group has lower blood white blood cells (WBC) ( P = 0.029), monocytes (p = 0.003), and NLR (p = 0.005). In univariate analysis, WBC, neutrophils, and NLR were statistically associated with PFS; performance status (PS), disease extent, albumin, WBC, neutrophils, and NLR were statistically associated with OS. In multivariate analysis, NLR (p = 0.007) was statistically associated with PFS; PS (p = 0.029) and NLR (p = 0.050) were statistically associated with OS. On examining the immune-related genes in ESCC tissues’ microenvironment, the ratios of mast cells, neutrophils, and macrophages relative to tumor-infiltrating lymphocytes (TILs) have significantly lower in the CBR group than in the non-CBR group. Conclusions: High NLR was associated with inferior prognosis in R/M ESCC patients receiving anti-PD-1/PD-L1-based therapy. The increased ratio of neutrophil to TILs in the ESCC tumor microenvironment of non-CBR patients may suggest a mechanistic role of neutrophils in affecting the efficacy of anti-PD-1/PD-L1 therapy. (Supported by the grant of MOST 105-2314-B-002 -186 -MY3)
MSc in health informatics
Authors: Negin Shamsian
Journal: BMJ (2011)

The master of science degree in health informatics is run by the Centre for Measurement and Information in Medicine at City University in London. The centre says that it is the longest established postgraduate course in health informatics in Europe.

Anyone with the minimum of a second class honours degree from a UK university in a medical or related subject or an accredited overseas qualification. Other degree subjects or professional qualifications may be accepted if you have subsequently had relevant experience in the health service or in the healthcare industry.

Part time entrants are expected to have at least two years’ professional experience in the health service or a related industry. In the case of applicants not holding an honours degree, three years of relevant professional experience would normally be …
Outcomes and predictors of hospital mortality in metastatic cancer patients receiving life sustaining treatments (LSTs).
Authors: Kah Poh Loh, Meng-Shiou Shieh, Ankit J. Kansagra, Peter Lindenauer, Penelope Pekow, Mihaela Stefan, Tara Lagu
Journal: Journal of Clinical Oncology (2015)

9583 Background: Hospital mortality for patients with metastatic cancer is high, especially for those who receive LSTs. Information on predicting the probability of surviving the hospitalization will help patients and clinicians make an informed decision. Methods: We used the 2010 California Healthcare Cost and Utilization Project - State Inpatient Database to identify metastatic cancer patients (≥18 years). Using ICD-9-CM diagnosis codes, we limited the dataset to patients receiving LSTs (mechanical ventilation, tracheostomy, PEG tube, TPN and acute use of dialysis). We described characteristics and outcomes in patients who survived hospitalization and who did not. We used multivariate logistic regression models to identify predictors for hospital mortality. Results: We identified 9,438 admissions among metastatic cancer patients who received LSTs. Mean age (65 years) and gender distribution were similar in both groups. Hospital mortality was 33%. Of those who survived, 31% were discharged to acute or post-acute facilities. Other outcomes are listed below. Predictors of hospital mortality included non-white race, unscheduled admissions, infectious, cardiovascular and circulatory or pulmonary diagnosis (vs. cancer-related) and greater burden of comorbidities. Comorbidities including ESRD (OR 2.03, 95% CI 1.12-2.94) and liver disease (OR 1.94 95% CI 1.55-2.33) were significantly associated with hospital mortality. Compared to lung cancer, colorectal (OR 0.32, 95% CI 0.26-0.38) and GU (OR 0.58, 95% CI 0.46-0.70) cancers were less likely to die in the hospital. Admissions with DNR status were strongly associated with hospital mortality (OR 2.32, 95% CI 2.01-2.63). Conclusions: Patients with metastatic cancer who survived in the hospital had longer LOS and one-third of them were discharged to facilities. Predictors of hospital mortality include lung cancer, ESRD, liver disease, DNR status, higher co-morbidity score and an unscheduled admission. Outcomes Died (n=3055) Alive (n=6273) P-value Comorbidity scorea 3.1 (2.3) 2.5 (2.2) <0.0001 Total charge per patientb ($100,000) 1.5 (2.1) 1.5 (1.9) <0.01 Length of staya (days) 13.4 (17.0) 15.5 (14.8) <0.0001 a Mean (SD). b Median (IQR).
THROMBOCYTOPENIA AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT: A COMPARISON BETWEEN BALLOON-EXPANDABLE AND SELF-EXPANDING PROSTHESIS
Authors: Margarida Pujol-López, Marco Hernández-Enríquez, Rut Andrea, Ander Regueiro, Joan Antoni Gómez-Hospital, Rafael Romaguera, Angel Cequier, Manel Sabaté
Journal: Journal of the American College of Cardiology (2018)
Provisional GMC registration for foundation doctors is of “questionable” value, says Medical Schools Council
Authors: Abi Rimmer
Journal: BMJ (2015)

The value of provisional General Medical Council registration for doctors in their first year of foundation training (FY1) is “questionable,” the Medical Schools Council has said.

In its annual review the council said that the reasons for introducing a provisional year of GMC registration for FY1s were no longer relevant, …
Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis
Authors: Shermel B. Sherman, Nadeen Sarsour, Marziyeh Salehi, Allen Schroering, Blair Mell, Bina Joe, Jennifer W. Hill
Journal: Gut Microbes (2018)

Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring.
Dental Personnel Treated for Idiopathic Pulmonary Fibrosis at a Tertiary Care Center — Virginia, 2000–2015
Authors: Randall J. Nett, Kristin J. Cummings, Brenna Cannon, Jean Cox-Ganser, Steven D. Nathan
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In April 2016, a Virginia dentist who had recently received a diagnosis of idiopathic pulmonary fibrosis (IPF) and was undergoing treatment at a specialty clinic at a Virginia tertiary care center contacted CDC to report concerns that IPF had been diagnosed in multiple Virginia dentists who had sought treatment at the same specialty clinic. IPF is a chronic, progressive lung disease of unknown cause and associated with a poor prognosis (1). Although IPF has been associated with certain occupations (2), no published data exist regarding IPF in dentists. The medical records for all 894 patients treated for IPF at the Virginia tertiary care center during September 1996-June 2017 were reviewed for evidence that the patient had worked as a dentist, dental hygienist, or dental technician; among these patients, eight (0.9%) were identified as dentists and one (0.1%) as a dental technician, and each had sought treatment during 2000-2015. Seven of these nine patients had died. A questionnaire was administered to one of the living patients, who reported polishing dental appliances and preparing amalgams and impressions without respiratory protection. Substances used during these tasks contained silica, polyvinyl siloxane, alginate, and other compounds with known or potential respiratory toxicity. Although no clear etiologies for this cluster exist, occupational exposures possibly contributed. This cluster of IPF cases reinforces the need to understand further the unique occupational exposures of dental personnel and the association between these exposures and the risk for developing IPF so that appropriate strategies can be developed for the prevention of potentially harmful exposures.
Cbl Ubiquitin Ligases Control B Cell Exit from the Germinal-Center Reaction
Authors: Xin Li, Adeline Gadzinsky, Liying Gong, Haijun Tong, Virginie Calderon, Yue Li, Daisuke Kitamura, Ulf Klein, Wallace Y. Langdon, Fajian Hou, Yong-Rui Zou, Hua Gu
Journal: Immunity (2018)
Brain Connectivity and Cognitive Flexibility in Nonirradiated Adult Survivors of Childhood Leukemia
Authors: Thibo Billiet, Iris Elens, Charlotte Sleurs, Anne Uyttebroeck, Rudi D’Hooge, Jurgen Lemiere, Sabine Deprez
Journal: JNCI Journal of the National Cancer Institute (2018)

This study aimed to assess functional and structural brain connectivity in adult childhood leukemia survivors and the link with cognitive functioning and previously identified risk factors such as intrathecal methotrexate dose and age at start of therapy. Thirty-one nonirradiated adult childhood leukemia survivors and 35 controls underwent cognitive testing and multimodal magnetic resonance imaging (resting state functional MRI, T1-weighted, diffusion-weighted, and myelin water imaging [MWI]). Analyses included dual regression, voxel-based morphometry, advanced diffusion, and MWI modeling techniques besides stepwise discriminant function analysis to identify the most affected executive cognitive domain. Correlations with discrete intrathecal MTX doses and (semi)continuous variables were calculated using Spearman's rank and Pearson's correlation, respectively. All correlation tests were two-sided. Positive and negative T-contrasts in functional and structural MRI analysis were one-sided. Survivors demonstrated lower functional connectivity between the default mode network (DMN) and inferior temporal gyrus (ITG; P < .008). Additionally, we observed higher fractional anisotropy (FA; P = .04) and lower orientation dispersion index (ODI; P = .008) at the left centrum semiovale, which could—given that several fiber bundles cross this region—suggest selective reduced integrity of the respective white matter tracts. Set shifting reaction time, a measure of cognitive flexibility, was mostly impaired and correlated with lower FA (r = –0.53, P = .003) and higher ODI (r = 0.40, P = .04) in survivors but not with DMN-ITG connectivity. There were no statistically significant differences between survivors and controls in WM or GM volume, nor was there a statistically significant correlation between imaging measurements and age at start of therapy or intrathecal methotrexate dose. Adult, nonirradiated childhood leukemia survivors show altered brain connectivity, which is linked with cognitive flexibility.
A Combination of SAHA and Quinacrine Is Effective in Inducing Cancer Cell Death in Upper Gastrointestinal Cancers
Authors: Shoumin Zhu, Zheng Chen, Lihong Wang, Dunfa Peng, Abbes Belkhiri, A. Craig Lockhart, Wael El-Rifai
Journal: Clinical Cancer Research (2018)

Purpose: We aimed to investigate the therapeutic efficacy of single agent and the combination of quinacrine and suberoylanilide hydroxamic acid (SAHA) in wt- and mut-p53 upper gastrointestinal cancer (UGC) cell models.Experimental Design: ATP-Glo, clonogenic cell survival, Annexin V, comet, DNA double-strand breaks (DSBs), qPCR, and Western blot analysis assays were utilized.Results: Using clonogenic cell survival, ATP-Glo cell viability, Annexin V, and sub-G0 population analysis, we demonstrated that a combination of quinacrine and SAHA significantly decreased colony formation and increased cancer cell death (range, 4-20 fold) in six UGC cell models, as compared with single-agent treatments, irrespective of the p53 status (P < 0.01). The combination of quinacrine and SAHA induced high levels of DSB DNA damage (>20-fold, P < 0.01). Western blot analysis showed activation of caspases-3, 9, and γ-H2AX in all cell models. Of note, although quinacrine treatment induced expression of wt-p53 protein, the combination of quinacrine and SAHA substantially decreased the levels of both wt-P53 and mut-P53. Furthermore, cell models that were resistant to cisplatin (CDDP) or gefitinib treatments were sensitive to this combination. Tumor xenograft data confirmed that a combination of quinacrine and SAHA is more effective than a single-agent treatment in abrogating tumor growth in vivo (P < 0.01).Conclusions: Our novel findings show that the combination of quinacrine and SAHA promotes DNA damage and is effective in inducing cancer cell death, irrespective of p53 status and resistance to CDDP or gefitinib in UGC models. Clin Cancer Res; 24(8); 1905-16. ©2018 AACR.