tbuckley/cabot-search huggingface dataset:
Differential blood cellular profile in patients with moderate-to-severe psoriasis treated with classical systemic therapies: a step forward in personalized medicine
Authors: B. Hernández-Breijo, T. Jurado, E. Rodríguez-Martín, A. Martínez-Feito, C. Plasencia-Rodríguez, A. Balsa, M.L. Alonso-Pacheco, L.M. Villar, P. Herranz-Pinto, D. Pascual-Salcedo
Journal: British Journal of Dermatology (2018)
I am a foundation year 1 trainee. I am planning a career in surgery and was thinking of taking my part 1 in January. I understand that the current system of exams is going to be scrapped for the new run-through training, however, and I wondered if it is worth sitting the current membership exams at all?
Authors: Umar Sadat
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Regulation of Th17 cells by P. UF1 against systemic <i>Listeria monocytogenes</i> infection
Authors: Natacha Colliou, Yong Ge, Minghao Gong, Mojgan Zadeh, Jing Li, Francis Alonzo, Mansour Mohamadzadeh
Journal: Gut Microbes (2018)

Regulation of Th17 and Th1 cell responses against intracellular pathogens, including Listeria monocytogenes (L. m), is critical to limit inflammation-induced tissue damage. We recently demonstrated the ability of P. UF1 bacterium derived from the intestinal bacterial commensals of preterm infants fed human breast milk to significantly mitigate pathogen-induced inflammation limiting colonic tissue damage. Here we further elucidated the potential of P. UF1 to also regulate innate and T cells, particularly Th17 and Th1 cells, against systemic L. m infection. Data demonstrate that P. UF1 not only robustly regulated protective Th17 and Th1 cells, but also sustained regulatory T cells (Treg cells) resulting in accelerated L. m clearance. Together, regulation of pathogenic inflammation by a novel probiotic bacterium such as P. UF1 may illuminate a new strategy to specifically control Th17-Th1 cells via IL-10+ Treg cells to limit systemic tissue damage induced by intracellular pathogens, including L. m.
Factors predicting poor survival in glioblastoma
Authors: Charlie Wilson, Giles Critchley
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM)/high-grade glioma grade IV is a debilitating diagnosis causing neurological deficits, personality changes and death. Despite recent advances in therapies, it continues to have one of the lowest one-year survival rates and, with an increasing incidence, it is imperative more research is undertaken to better understand the disease and pathophysiology. Identify demographics and molecular profile characteristics of GBMs in patients who have a survival of less than six months (short-term survivors [STS]) that carry prognostic value. One hundred and sixty-one consecutive patients with a diagnosis of GBM from Brighton and Sussex University Hospitals were audited from January 2013 to July 2016. Patients had treatments, dates of diagnosis and dates of death recorded. All molecular pathology reports were reviewed and collated to assess trends. Data were classified into two groups, those who survived for less than six months from diagnosis and those who survived longer. Date of surgery was used as a surrogate for diagnosis date. 42.2% (n=68) patients had a survival less than six months. Of these, 34 (50.0%) had a craniotomy, in comparison to 76 (81.7%) of those who survived longer than six months. Isocitrate dehydrogenase-1 (IDH-1) testing revealed 5% of STS (n=3) had mutations, in contrast to 15% in longer-term survivors (n=14). Hypermethylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter was present in both groups with 55.6% and 62.1% in STS (n=35) and long-term survivors (n=54) respectively. The current literature is focused on variables predicting the greatest survival in GBM patients, however there is a sparsity of studies looking at which patients will have a poorer prognosis. It is hoped analysing key molecular markers and treatment will identify factors one can use to anticipate a less favourable outcome.
68Ga DOTATATE PET/CT Imaging of Elastofibroma Dorsi
Authors: Mitsutomi Ishiyama, Hubert Vesselle
Journal: Clinical Nuclear Medicine (2018)

Abstract Sixty six-year-old woman status post ileocecal resection for well-differentiated neuroendocrine tumor in the terminal ileum 7 years ago, who is on octreotide therapy for liver metastases. 68 Ga DOTATATE PET/CT showed soft tissue masses with mildly increased radiotracer uptake in the bilateral subscapular/infrascapular regions. In retrospective image review, these soft tissue masses were first noted 7 years prior and have gradually increased in size over the years. Given the characteristic location and imaging findings, these masses are consistent with benign elastofibroma dorsi instead of metastasis.
Edinburgh summer school in clinical education
Authors: Samantha Smith, Victoria R Tallentire
Journal: BMJ (2011)

This five day course, held annually, is designed for anyone involved in teaching medical students, postgraduate trainees, or other healthcare professionals. It attracts clinicians at all levels, from foundation doctors to consultants.

We are both fellows in medical education and took this course near the beginning of our respective fellowships (August 2009 and August 2010). The dates of the course coincide with the array of festivals held in Edinburgh throughout August, which is an added bonus for course participants.

Bedside teaching, workplace based assessment, and educational supervision are part of the daily work of many doctors. We wanted to gain a broad overview of teaching, learning, and assessment in medicine to apply the lessons to teaching …
Scottish government will not impose contract changes on junior doctors
Authors: Abi Rimmer
Journal: BMJ (2015)

payments for excellence could be progressed separately at first, with the next step being to agree assumptions for the pay modelling that will give some clarity on impacts on doctors in different specialties and at different stages of their career.13.While we consider that removal of the 'opt-out' is important and significant, we know that hospital doctors in many places are already delivering services for seven days of the week, in the evenings and at night, so the current contract does not make this impossible.We urge that agreement on contractual reform should not get in the way of making progress in testing and developing the expansion of seven-day services, given their importance for patient outcomes.United Kingdom-wide contracts 14.We encourage all four countries of the UK to work together in order to make progress on both contracts.We support UK-wide contracts for junior doctors and consultants as we feel that they best serve the needs of patients.
COMPARATIVE EFFECTIVENESS AND SAFETY OF NOACS VERSUS WARFARIN FOR SECONDARY STROKE PREVENTION IN ATRIAL FIBRILLATION: A NATIONWIDE DANISH COHORT STUDY
Authors: Peter Brønnum Nielsen, Frede A. Tøgersen, Flemming Skjøth, Mette Søgaard, Torben Bjerregaard Larsen, Greg Lip
Journal: Journal of the American College of Cardiology (2018)
SAS doctors are unhappy with BMA’s opposition to credentialing
Authors: Abi Rimmer
Journal: BMJ (2014)

Staff, associate specialist, and specialty doctors (SAS doctors) have declared themselves “unhappy” with the BMA Council’s decision to oppose the introduction of credentialing. 

Delegates at the BMA SAS doctors’ conference voted in favour of a motion that said SAS doctors were “unhappy with the BMA Council decision which rejects credentialing of SAS doctors as a means of recognition of their competences they rightly deserve, in the ever changing NHS medico-political climate …
Ocular tuberculosis – A closer look to an increasing reality
Authors: F. Teixeira-Lopes, S. Alfarroba, A. Dinis, M.C. Gomes, A. Tavares
Journal: Pulmonology (2018)

Ocular tuberculosis (OTB) is a rare form of tuberculosis. Diagnosis is usually presumptive based on epidemiology, clinical findings and positivity of immune response. The aim of the study was to characterize the OTB cases identified in Lisbon.Retrospective study on OTB cases diagnosed in Lisbon from 2012 to 2015. The authors gathered data regarding demographic characteristics, diagnostic criteria, type of treatment as well as therapeutic results.There were 39 reported cases of presumed OTB which accounted for 12.2% of all reported TB cases. Patients had a mean age of 55.5 years. All had ocular manifestations (mainly uveitis). Diagnostic criteria included positive tuberculin skin test (TST) and/or Interferon Gamma Release Assay (IGRA). Culture testing or PCR could not be determined in any patient. Patients had OTB treatment for an average of 9.08 months. Clinical improvement was reported in 91.4% of treated patients. There were no relapses.This is the first published series about OTB in Lisbon. All cases had a presumptive diagnosis made through TST and/or IGRA testing. Most of treated patients improved, with no signs of relapse and a median 29.9-month follow up. OTB seems to be a growing diagnosis and treatment may be beneficial even in patients with a presumptive diagnosis.
Efficacy and prognostic factor analysis in second-line chemotherapy for elderly patients with metastatic gastric cancer.
Authors: Ayaka Shoji, Hiroko Hasegawa, Seiya Kato, Ryosuke Kiyota, Kazuma Shinkai, Taku Tashiro, Akio Ishihara, Tetsuya Iwasaki, Satoshi Tanaka, Tomofumi Akasaka, Yuko Sakakibara, Shoichi Nakazuru, Hisashi Ishida, Motohiro Hirao, Eiji Mita
Journal: Journal of Clinical Oncology (2018)

143 Background: Recently, the proportion of elderly patients (pts) with advanced gastric cancer has increased in Japan. Survival benefits of second-line chemotherapy (CTX) such as weekly paclitaxel (PTX)±Ramucirumab (RAM) or irinotecan (CPT) were shown in several phase 3 trials for metastatic gastric cancer (mGC). However, efficacy and prognostic factors in the second line CTX for elderly pts are not well studied. Methods: We retrospectively reviewed for mGC pts aged ≥ 70 years who underwent PTX+RAM, PTX or CPT as second-line CTX. Eligibility criteria were as follows: PS 0-2, refractory to an S-1containing CTX. Response rate (RR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were performed to determine prognostic factors of survival. Results: There were 250 pts with mGC treated at our institution between April 2007 and March 2017. Of all, total of 85 pts were eligible. Median age was 75 years (71-85). The RR was 28.0% in the PTX+RAM group (n=28), 17.2% in the PTX group (n=29) and 18.5% in the CPT group (n=28). Median PFS was 5.1 months(M) and MST was 12.2 M in the PTX+RAM group, compared with 4.1 M and 9.7 M in the PTX group, or 3.3M and 9.8M in the CPT group. The ORR, PFS and OS were better in the PTX+RAM group though differences between groups were not statistically significant. Grade 3 or higher non-hematological AEs such as fatigue or diarrhea were more frequent in the CPT group on the other hand, hematological AEs were more frequent in the PTX+RAM group. On multivariate analysis, PS (HR,3.13; 95%CI, 1.60-5.77), LDH (HR,3.19; 95%CI, 1.80-5.57), and CEA (HR,2.35; 95%CI, 1.30-4.16) were found to be significant prognostic factors for elderly pts with mGC who underwent second-line CTX. Conclusions: PTX+RAM therapy seemed to be more effective than the other regimens. Furthermore, this analysis for prognostic factors may help clinicians to better select elderly pts who may benefit from a second-line CTX.
Concordance between radiologic and pathologic complete response in patients with breast cancer treated with neoadjuvant chemotherapy.
Authors: Laia Garrigos, Maria Dolors Sabadell, Ana Rodriguez-Arana, Josep Maria Corominas, Maria Martinez-Garcia, Iria Gonzalez, Tamara Martos, Joan Albanell, Ignacio Tusquets, Sonia Servitja
Journal: Journal of Clinical Oncology (2014)

e12028 Background: Magnetic Resonance Imaging (MRI) is accepted as the best exploration to predict pathological response to neoadjuvant chemotherapy(NAC) in breast cancer. Our goal is to analyze the correlation between radiological complete response (rCR) and pathological complete response (pCR), globally and according to the different tumor immunophenotypes (IF). Methods: This retrospective study included patients with stage I-III who were treated with NAC at our breast cancer unit between January 2006 and December 2012. Patients underwent a baseline MRI and after NAC. The radiological response was assessed according to the RECIST version 1.1 and the pathological response according to the Miller & Payne grading system. Results: 214 patients were included with a mean age of 56.3 years. Concerning clinical stage, 55.1% of the patients were classified as stage II and 40.7% as stage III. Most patients(82.7%) received NAC with anthracyclines and taxanes. Regarding the type of surgery 69.2% of patients underwent breast conserving surgery. pCR was achieved in 18.7% patients, 52% in HER2+ tumors, 31.3% in triple-negative(TN), 28.6% in luminal-B-HER2+, 5.4% in luminal-B-HER2- and 1,4% in luminal-A. The rCR rate was 24.9%. The Table reports results of MRI accuracy predicting pCR estimating sensitivity (Se) and specificity (Sp). We have analyzed the reliability of MRI to detect complete response in breast and axillary lymph nodes independently, reporting Se of 55,8% and 69.3 % respectively (p=0,113) and Sp of 81.3% and 41% (p<0,001). We found a false positive rate of 17,2% and a false negative rate of 7.9%. We classified 30 patients as G4, of which 7 (23.3%) are classified mistakenly by MRI as rCR. Conclusions: MRI achieves Se 57.6% and Sp 82.8% predicting pCR. The values of Se are higher in TN and HER2+ tumors while the values of Sp are higher in Luminal-B and TN tumors. The Sp of MRI for detecting pCR is higher in breast than in axillary lymph nodes. n Overall 214 HER2 + 29 Luminal A 71 LuminalB- HER2+ 29 LuminalB- HER2- 37 Triple negative 48 Se (%) 57,6 (23/40) 66,7 (10/15) 0 (0/1) 28,6 (2/7) 100 (2/2) 60 (9/15) Sp (%) 82,8 (144/174) 78,6 (11/14) 78,6 (55/70) 86,3 (19/22) 91,4 (32/35) 81,8 (27/33)
Imaging of C-X-C Motif Chemokine Receptor CXCR4 Expression After Myocardial Infarction With [68Ga]Pentixafor-PET/CT in Correlation With Cardiac MRI
Authors: Theresa Reiter, Malte Kircher, Andreas Schirbel, Rudolf A. Werner, Saskia Kropf, Georg Ertl, Andreas K. Buck, Hans-Jürgen Wester, Wolfgang R. Bauer, Constantin Lapa
Journal: JACC. Cardiovascular imaging (2018)
SPECT/CT With the PSMA Ligand 99mTc-MIP-1404 for Whole-Body Primary Staging of Patients With Prostate Cancer
Authors: Christian Schmidkonz, Michael Cordes, Michael Beck, Theresa Ida Goetz, Daniela Schmidt, Olaf Prante, Tobias Bäuerle, Michael Uder, Bernd Wullich, Peter Goebell, Torsten Kuwert, Philipp Ritt
Journal: Clinical Nuclear Medicine (2018)

Background 99m Tc-MIP-1404 (Progenics Pharmaceuticals, Inc, New York, NY) is a novel ligand binding to prostate-specific membrane antigen suitable for SPECT. There are, as yet, no data concerning its use in whole-body primary staging and its interobserver variability in patients with prostate cancer (PC) prior to therapy. Methods A search of our clinical database from April 2013 to May 2017 yielded 93 patients with histologically confirmed cancer in whom 99m Tc-MIP-1404 SPECT/CT had been performed for primary whole-body staging before therapy. Whole-body planar and SPECT/CT images of the lower abdomen and thorax had been obtained 3 to 4 hours postinjection of 706 ± 72 MBq 99m Tc-MIP-1404. Images were visually analyzed for extent and location of abnormal uptake by 2 experienced nuclear physicians. Interobserver agreement for detection of primary tumor and metastatic lesions was assessed. In addition, SUVs of prostate-specific membrane antigen–positive regions of the prostate were determined in all patients, and from these, a variable reflecting total tumor load in the prostate gland was calculated (TU prostate ). Follow-up reports of subsequent therapeutic interventions were available in 52 (56%) of all patients with a median follow-up of 18 months. Results In 90 (97%) of 93 patients, prostate uptake above background was detected as correlate of the histologically diagnosed PC. Forty-eight lymph node and 29 bone metastases were detected in 16 and 9 patients, respectively. In addition, 3 patients had disseminated bone metastases. No distant organ metastases were found. Interobserver agreement was high for the overall scan result (97%), as well as for the detection of the primary tumor (97%), of lymph node metastases (97%), and of bone metastases (99%). Recurrence of PC occurred in 5 patients in whom follow-up was available (10%). TU prostate was significantly higher in patients with Gleason scores of 8 or greater compared with patients with Gleason scores of 7 or less and at prostate-specific antigen (PSA) serum levels of 10 ng/mL or greater compared with PSA serum levels of 10 ng/mL or less. TU prostate of greater than 26 in the primary tumor predicted the occurrence of lymph node or bone metastases with a sensitivity of 82% and specificity of 76%. Conclusions MIP-1404 SPECT/CT has a high accuracy and low interobserver variability in the diagnosis of PC and allows detection of lymph node and bone metastases in a significant proportion of as yet untreated PC patients. TU prostate is correlated with Gleason score and PSA serum concentration and allows prediction of the occurrence of lymph node and bone metastases with moderate accuracy at primary staging.
CD73 expression in primary and metastatic renal cell carcinoma (RCC).
Authors: Abhishek Tripathi, Sarah E Johnston, Yan D Zhao, Oudai Hassan, Linda F Thompson, Aly-Khan A. Lalani, Xiao X. Wei, Marios Giannakis, Sabina Signoretti, Toni K. Choueiri, Lauren Christine Harshman
Journal: Journal of Clinical Oncology (2018)

643 Background: Agents targeting the PD-1 pathway have improved outcomes in RCC. CD73 may be an additional mechanism which tumors can exploit for immune evasion. It is regulated by hypoxia inducible factor (HIF) and converts AMP to adenosine. The resulting increase in extracellular adenosine can inhibit T-cell effector function. We evaluated CD73 expression in primary and metastatic tumor samples in patients with RCC. Methods: A commercial TMA (US Biomax) consisting of 31 primary clear cell RCC samples (2 with sarcomatoid features) with 8 matched and 1 unmatched metastases was used to assess CD73 expression. A genitourinary pathologist (OH) confirmed pathology and grade. Immunohistochemistry (IHC) was performed using a monoclonal anti-CD73 antibody (Cell Signaling; D7F9A). A combined score (CS: % of cells positive x intensity) was employed to quantify CD73 expression. Expression levels between matched primary and metastatic tissue was compared using Wilcoxon signed-rank test. Correlation of CD73 expression (CS &gt; 0) in primary tumor with baseline clinical and pathologic characteristics was assessed using Kruskal-Wallis and Fisher's exact tests. Overall survival (OS) was estimated using the Kaplan-Meier method. Comparison between CD73 expression groups used log rank test. Results: CD73 expression was seen in 19% (n = 6) of primary and 66.7% (n = 6) of metastatic samples. Among matched primary and metastatic samples (n = 8 each), median CS was 25 (Q1-Q3:0-105) in metastatic samples while none of the corresponding primary samples demonstrated CD73 expression (median CS = 0, p = 0.062). CD73 expression in primary tumor samples did not correlate with baseline clinical or pathologic features. Five-year OS was 50% in patients who expressed CD73 in primary tumors compared to 84% in those who did not (p = 0.26). Conclusions: We observed a numerical increase in CD73 expression in metastatic tissue compared to primary RCC samples and worse 5 year OS. The small number of samples has limited statistical significance. Further studies are needed to examine the impact of CD73 expression on outcomes in RCC patients treated with currently approved checkpoint inhibitors and the investigational CD73 antagonists that are in early phases of development.
Predictive Gene Signatures Determine Tumor Sensitivity to MDM2 Inhibition
Authors: Jo Ishizawa, Kenji Nakamaru, Takahiko Seki, Koichi Tazaki, Kensuke Kojima, Dhruv Chachad, Ran Zhao, Lauren Heese, Wencai Ma, Man Chun John Ma, Courtney DiNardo, Sherry Pierce, Keyur P. Patel, Archie Tse, R. Eric Davis, Arvind Rao, Michael Andreeff
Journal: Cancer Research (2018)

Early clinical trials using murine double minute 2 (MDM2) inhibitors demonstrated proof-of-concept of p53-induced apoptosis by MDM2 inhibition in cancer cells; however, not all wild-type TP53 tumors are sensitive to MDM2 inhibition. Therefore, more potent inhibitors and biomarkers predictive of tumor sensitivity are needed. The novel MDM2 inhibitor DS-3032b is 10-fold more potent than the first-generation inhibitor nutlin-3a. TP53 mutations were predictive of resistance to DS-3032b, and allele frequencies of TP53 mutations were negatively correlated with sensitivity to DS-3032b. However, sensitivity to DS-3032b of TP53 wild-type tumors varied greatly. We thus used two methods to create predictive gene signatures. First, by comparing sensitivity to MDM2 inhibition with basal mRNA expression profiles in 240 cancer cell lines, a 175-gene signature was defined and validated in patient-derived tumor xenograft models and ex vivo human acute myeloid leukemia (AML) cells. Second, an AML-specific 1,532-gene signature was defined by performing random forest analysis with cross-validation using gene expression profiles of 41 primary AML samples. The combination of TP53 mutation status with the two gene signatures provided the best positive predictive values (81% and 82%, compared with 62% for TP53 mutation status alone). In addition, the top-ranked 50 genes selected from the AML-specific 1,532-gene signature conserved high predictive performance, suggesting that a more feasible size of gene signature can be generated through this method for clinical implementation. Our model is being tested in ongoing clinical trials of MDM2 inhibitors.Significance: This study demonstrates that gene expression profiling combined with TP53 mutational status predicts antitumor effects of MDM2 inhibitors in vitro and in vivoCancer Res; 78(10); 2721-31. ©2018 AACR.
Progress Toward Elucidating Commonalities in Mental Disorders Using Brain Imaging and Publicly Available Data
Authors: David R. Roalf
Journal: JAMA Psychiatry (2018)

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