tbuckley/cabot-search huggingface dataset:
P082 Circulating mir-145 as a marker of therapeutic response in patients with ankylosing spondylitis receiving anti-tnf therapy
Authors: K Prajzlerová, V Hrušková, M Komarc, Š Forejtová, K Pavelka, J Vencovský, L Šenolt, M Filková
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The altered expression of miRNAs is involved in the pathophysiology of inflammatory conditions. Moreover, circulating miRNAs appear promising therapeutic and prognostic biomarkers. <h3>Objectives</h3> To investigate the effect of anti-TNF therapy on the levels of circulating miRNAs in patients with ankylosing spondylitis (AS). <h3>Methods</h3> Our study included 19 AS patients. Clinical and laboratory parameters of disease activity were assessed at baseline (M0) and after 3 (M3) and 12 months (M12) of therapy. Total RNA from plasma was isolated using miRNeasy Serum/Plasma Kit (Qiagen). First, a comprehensive analysis of miRNAs was performed using TaqMan Low Density Array (TLDA) in 3 patients. Next, single assays were used for validation of selected miRNAs. dCt method was used for relative quantification. Data were analysed using ANOVA with Bonferroni corrections and Spearman's correlation coefficient. <h3>Results</h3> All AS patients had high disease activity at baseline and had a good therapeutic response to anti TNF therapy at M3 and M12 (BASDAI p&lt;0.001, ASDAS p&lt;0.001). Out of all 380 miRNAs analysed by TLDA, 125 miRNAs were detected in all samples, 148 miRNAs were detected at M0, 154 at M3 and 151 at M12. Validation of 17 selected miRNAs confirmed significant downregulation of miR-145 at M3 (TLDA 1.59-change; single assays 1.62-change, p=0.024), but the downregulation did not reach statistical significance at M12 (TLDA 1.46-change; single assays 1.11-change, p&gt;0.05). The decrease in miR-145 expression from M0 to M3 significantly correlated with disease activity improvement over time from M3 to M12 as per BASDAI (r=0.672, p=0.002) and ASDAS scores (r=0.607, p=0.006) and VAS at M12 (r=0.515, p=0.024). Although the overall clinical efficacy of anti-TNF therapy sustained, 6 patients revealed some ASDAS worsening at M12. This may have resulted to correlation of higher miR-145 levels at M3 with disease activity worsening as per increase in ASDAS from M3 to M12 (r=0.593, p=0.007) and higher ASDAS (r=0.533, p=0.019) and VAS (r=0.564, p=0.012) at M12. <h3>Conclusions</h3> We propose that an early change in miR-145 levels may be a predictor for the future outcome of AS patients as it's early decrease after anti-TNF initiation correlated with further disease activity improvement. These data suggest the potential to use circulating miRNAs as biomarkers of treatment response in AS. <h3>Acknowledgements</h3> Grants 17-33127A and SVV 260263. <h3>Disclosure of interest</h3> None declared
Writing clinical records on a consultant ward round
Authors: Rubeta N H Matin
Journal: BMJ (2006)

In this climate of increasing litigation, it is imperative that good medical records are kept. Junior doctors are all too often mistaken for scribes. They frequently trail far behind the consultant, not hearing what has been discussed and writing sparse and irrelevant entries in the notes. Here are some tips on how to make the most of the crucial consultant ward round. …
Abstract P1-07-35: Adipokine receptor <i>CAP1</i> expression as predictor of survival outcome among breast cancer patients
Authors: AH Rosendahl, M Bergqvist, S Kimbung, S Borgquist
Journal: Cancer Research (2018)

Abstract Background: Obesity is a challenging health concern in breast cancer. Not only are obese women at higher risk of breast cancer, but if diagnosed with the disease, obesity is also impairing the prognosis of a breast cancer. Understanding the underlying biology behind these associations are key to improve survival rates in breast cancer. In obesity, the more abundant, activated adipose tissue may lead to insulin resistance and secretion of soluble mediators that may contribute to impaired breast cancer outcomes observed among obese women. The adipokine resistin is implied to be an important link between obesity and insulin resistance, and to be elevated among breast cancer patients. Yet, the expression of the newly identified resistin receptor CAP1 and its impact on breast cancer prognosis is poorly understood. Purpose: To evaluate the impact by the adipokine receptor CAP1 tumor expression on breast cancer outcomes. Experimental Design: CAP1 mRNA expression was explored among 1,881 primary breast tumors. Associations between CAP1 expression, categorized into tertiles, and survival outcomes were estimated using the Kaplan-Meier method and log-rank test, and by multivariable Cox regression models providing adjusted hazard ratios (HRadj) with 95% confidence intervals (CI). Independent biological network interaction analyzes were conducted in a subset of 1,105 invasive breast carcinomas within The Cancer Genome Atlas (TCGA) project. Results: CAP1 was linked to poor tumor characteristics with higher CAP1 expression found among estrogen receptor (ER)-negative tumors, relative to ER-positive tumors, as well as with increasing tumor grade (P=0.025). High CAP1 tumor expression was further associated with shorter overall survival (HRadj 1.54; 95% CI, 1.11-2.13) and relapse-free survival (HRadj 1.47; 95% CI, 1.10-1.96), compared with low or intermediate CAP1 expression, particularly among ER-positive tumors or lymph node positive tumors. Additionally, CAP1 was identified in complex with genes involved in growth promoting and cell motility processes. Conclusion: These results highlight the potential role of the resistin receptor CAP1 regarding breast cancer outcomes. Further investigations are needed to elucidate the biological and clinical implication of the resistin-CAP1 link in obesity-associated breast cancer. Citation Format: Rosendahl AH, Bergqvist M, Kimbung S, Borgquist S. Adipokine receptor CAP1 expression as predictor of survival outcome among breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-35.
Glycogen synthase kinase 3β promotes liver innate immune activation by restraining AMP-activated protein kinase activation
Authors: Haoming Zhou, Han Wang, Ming Ni, Shi Yue, Yongxiang Xia, Ronald W. Busuttil, Jerzy W. Kupiec-Weglinski, Ling Lu, Xuehao Wang, Yuan Zhai
Journal: Journal of Hepatology (2018)
Evaluation of efficacy and safety of budesonide/formoterol combination therapy in asthma patients
Authors: Marko Jakopović, Fadila Pavičić, Miroslav Samaržija, G Redžepi, Neven Tudorić, Žarko Vrbica, Sanja Grle-Popović
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Evaluation of efficacy and safety of budesonide/formoterol combination therapy in asthma patients
N‐acetyl‐L‐cysteine improves bone marrow endothelial progenitor cells in prolonged isolated thrombocytopenia patients post allogeneic hematopoietic stem cell transplantation
Authors: Yuan Kong, Min‐Min Shi, Yuan‐Yuan Zhang, Xie‐Na Cao, Yu Wang, Xiao‐Hui Zhang, Lan‐Ping Xu, Xiao‐Jun Huang
Journal: American Journal of Hematology (2018)

Prolonged isolated thrombocytopenia (PT) is a serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to murine studies, endothelial progenitor cells (EPCs) play a crucial role in the regulation of hematopoiesis and thrombopoiesis in the bone marrow (BM) microenvironment. We previously showed that the reduced frequency of BM EPCs was an independent risk factor for the occurrence of PT following allo-HSCT. However, the functional role of BM EPCs and methods to improve the impaired BM EPCs in PT patients are unknown. In the current case-control study, we investigated whether the BM EPCs in PT patients differed from those in good graft function patients. Moreover, we evaluated whether N-acetyl-L-cysteine (NAC, a reactive oxygen species [ROS] scavenger) could enhance BM EPCs from PT patients in vitro and in vivo. The PT patients exhibited dysfunctional BM EPCs characterized by high levels of ROS and apoptosis and decreased migration and angiogenesis capabilities. In vitro treatment with NAC improved the quantity and function of the BM EPCs cultivated from the PT patients by downregulating the p38 MAPK pathway and rescued the impaired BM EPCs to support megakaryocytopoiesis. Furthermore, according to the results of a preliminary clinical study, NAC is safe and effective in PT patients. In summary, these results suggested that the reduced and dysfunctional BM EPCs are involved in the occurrence of PT. The defective BM EPCs in the PT patients can be quantitatively and functionally improved by NAC, indicating that NAC is a promising therapeutic approach for PT patients following allo-HSCT.
ANABOLIC ANDROGENIC STEROID ABUSE AND REVERSIBLE CARDIOMYOPATHY: AN EMERGING AND UNDER-RECOGNIZED CARDIOVASCULAR PUBLIC HEALTH PROBLEM AMONG FITNESS ENTHUSIASTS
Authors: Dakshin Gangadharamurthy, Natesa Pandian, Saurabh Malhotra, Syed Tahir, Jayanta Mukherjee
Journal: Journal of the American College of Cardiology (2018)
Exploration of the cGAS-STING pathway in prostate cancer.
Authors: Emma Reilly, Andrena McCavigan, Steven M. Walker, Nuala McCabe, Eileen Parkes, D. Paul Harkin, Richard D Kennedy, Laura A Knight
Journal: Journal of Clinical Oncology (2018)

103 Background: Recent studies have demonstrated limited success of immune checkpoint therapies in unselected prostate cancer. We therefore assessed an immune based DNA Damage Repair Deficiency (DDRD) assay, that we have previously reported represents activation of the cGAS STING pathway, in the TCGA prostate cancer dataset to investigate the presence of targetable immune biology in prostate cancer. In addition we applied a second assay (the prostate cancer metastatic signature-PCM) that predicts the risk of metastatic recurrence for early prostate cancer, in order to assess if immune therapy could have a role in treating high risk disease. Methods: 498 samples with RNA sequencing data were scored with the PCM and DDRD assays. Integrative analysis was performed on 488 samples with RNA sequencing, promoter site methylation, somatic mutation and somatic copy number variation. Gene expression of n = 6 immune checkpoint targets was investigated with the subgroups identified using T-tests. The prevalence of immune infiltration in each subgroup was tested by applying a cut off to the leukocyte fraction. Cox proportional hazards regression analysis of 441 patients was assessed for biochemical recurrence. Results: Integrative analysis identified four patient subgroups characterised primarily by variances in copy number and genomic mutation. One of these subgroups ‘Metastatic-like DDRD’ had significantly higher PCM scores and DDRD immune scores compared to the other subgroups (p &lt; 2E-12). This subgroup of patients showed elevated leukocyte fraction and expression of immune checkpoint genes: CD274 (PDL1), CTLA4, ICOS, IDO1, HAVCR2 (TIM3) &amp; LAG3 (p &lt; 2E-6). Genomic instability with amplification of 8q and a larger prevalence of somatic mutations including that of TP53 was also detected in this subgroup. These patients had an increased risk of biochemical relapse in both univariate (p &lt; 2E-5) and multivariate (p &lt; 0.008) analysis. Conclusions: We identified a poor prognostic subgroup, representing 17% of early prostate cancer patients that are at increased risk of developing metastatic disease and present with targetable immune biology. These patients may represent a viable target population for immune checkpoint and DNA damaging therapies in prostate cancer.
Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial—PRODIGE 20 study results
Authors: T. Aparicio, O. Bouché, J. Taieb, E. Maillard, S. Kirscher, P.-L. Etienne, R. Faroux, F. Khemissa Akouz, F. El Hajbi, C. Locher, Y. Rinaldi, T. Lecomte, S. Lavau-Denes, M. Baconnier, A. Oden-Gangloff, D. Genet, E. Paillaud, F. Retornaz, E. François, L. Bedenne
Journal: Annals of Oncology (2017)

BackgroundMetastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population.Patients and methodsPatients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.ResultsAbout 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75–91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT).ConclusionBevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.
I want to be a GP. If I do an FTSTA for one year (next year) will I be able to apply for an ST2 post in general practice or do I start again at ST1 level?
Authors: Rodger Charlton
Journal: BMJ (2007)

Have a career related problem that needs answering? Can9t find the 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>
FDG Accumulation in the Lumen of the Gallbladder Without Related Pathology
Authors: Xia Bai, Xuemei Wang, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2018)

Abstract FDG accumulation in the gallbladder has been reported as an indication of either malignancy or inflammation. We here report a case of FDG accumulation in the gallbladder without pathology in the gallbladder. A 15-year-old girl with Hodgkin disease underwent staging FDG PET/CT, which revealed not only the abnormal activity in the lymph nodes and left ilium, which were consistent with the malignant involvement, but also increased activity in the gallbladder. The patient had no symptoms related to hepatobiliary system at the time of scan and did not suffer any problem related to hepatobiliary system during 14 months of follow-up.
Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer
Authors: Neil H. Segal, Aiwu R. He, Toshihiko Doi, Ronald Levy, Shailender Bhatia, Michael J. Pishvaian, Rossano Cesari, Ying Chen, Craig B. Davis, Bo Huang, Aron D. Thall, Ajay K. Gopal
Journal: Clinical Cancer Research (2018)

Purpose: Utomilumab (PF-05082566) is an agonistic mAb that engages the immune costimulatory molecule 4-1BB/CD137. In this first-in-human, phase I, open-label, multicenter, multiple-dose study (NCT01307267) we evaluated safety, tolerability, pharmacokinetics, preliminary clinical activity, and pharmacodynamics of single-agent utomilumab in patients with advanced malignancies.Experimental Design: Dose escalation was based on a standard 3+3 design for doses of utomilumab from 0.006 to 0.3 mg/kg every 4 weeks and a time-to-event continual reassessment method for utomilumab 0.6 to 10 mg/kg every 4 weeks. The primary study endpoint was dose-limiting toxicity (DLT) in the first two cycles.Results: Utomilumab demonstrated a well-tolerated safety profile (N = 55). None of the patients experienced a DLT at the dose levels evaluated. The most common treatment-related adverse events were fatigue, pyrexia, decreased appetite, dizziness, and rash (<10% of patients). Only one (1.8%) patient experienced a grade 3-4 treatment-related adverse event (fatigue), and no clinically relevant elevations in transaminases were noted. Utomilumab demonstrated linear pharmacokinetics at doses ranging from 0.006 to 10 mg/kg, with similar safety and pharmacokinetics in anti-drug antibody (ADA)-negative and ADA-positive patients. The overall objective response rate was 3.8% (95% CI, 0.5%-13.0%) in patients with solid tumors and 13.3% in patients with Merkel cell carcinoma, including a complete response and a partial response. Circulating biomarkers support 4-1BB/CD137 engagement by utomilumab and suggest that circulating lymphocyte levels may influence probability of clinical benefit.Conclusions: The favorable safety profile and preliminary antitumor activity demonstrated by utomilumab warrant further evaluation in patients with advanced malignancies. Clin Cancer Res; 24(8); 1816-23. ©2018 AACR.
Abstract 14005: Beat-to-beat Variability of Hemodynamic Parameters Predict the Outcomes of Head Up Tilt Table Test in Patients With Vasovagal Syncope
Authors: Chunying Zhang, Qing Zhang, Yanpeng Chu, Lu Ren, Lin Tong, Lin Wu
Journal: Circulation (2016)

Introduction: The risk of severe syncopal episodes during head up tilt table test (HUTT) in patients with vasovagal syncope (VVS) limits its use in clinic. The objective of this study was to identify the early hemodynamic predictors of positive results during HUTT. Methods: HUTT was conducted prospectively in 82 consecutive patients with suspicious VVS and 19 normal control. Continuous noninvasive hemodynamic monitor was used to monitor the beat-to-beat changes of heart rate (HR) and blood pressure (BP). Values of short-term heart rate variability (HRV) and blood pressure variability (BPV) were calculated using formula of HR(BP)V= Σ ∣ HR(BP)n+1-HR(BP)n ∣ /(n x √2). Receiver-operating characteristic (ROC) curve analysis was used to test the predictive values. Results: Fifty-six out of 82 patients were HUTT positive. The results indicated that four parameters, including percentage of HR increment (ΔHR%) and systolic BPV increment (ΔSBPV%) were early (5 minutes after tilt-up), the ΔSBPV% and percentage of mean arterial pressure variability increment (ΔMAPV%) were late (30 minutes after tilt-up) predictors of a syncopal episode during HUTT. The detailed predictive information of these parameters were listed in table 1. Conclusion: Beat-to-beat variability of HR, SBPV and MAPV increment during early and late tilt-up period are valuable pre-syncopal parameters to predict the outcome of HUTT in patients with VVS.
GPs in UK lead world in use of health information technology, survey shows
Authors: Caroline White
Journal: BMJ (2012)

General practitioners in the United Kingdom seem to have incorporated information technology into their practice far more than have their peers in other developed countries, indicates an international survey of almost 8500 primary care doctors published in Health Affairs .1

The 2012 Commonwealth International Health Policy survey sought the views of primary care doctors in Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Switzerland, the UK, and the United States between March and July 2012.

The response rates varied considerably by country, but the results showed that GPs in the UK topped the league table for digital knowhow.

More than two thirds (68%) of …
THE RATIO OF N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE TO HIGH SENSITIVITY CARDIAC TROPONIN TO DISTINGUISH TYPE 1 FROM TYPE 2 ACUTE MYOCARDIAL INFARCTION
Authors: Joseph Gibbs, James McCord, Michael Hudson, Michele Moyer, Gordon Jacobsen, Robin Trupp, Richard Nowak
Journal: Journal of the American College of Cardiology (2018)
Draining Papule on the Lateral Neck of an Infant
Authors: Elana Putterman, Jiade Yu, Leslie Castelo-Soccio
Journal: JAMA Pediatrics (2018)

An 8-month-old boy presented with a papule on his right lateral neck that was present from birth that drained clear fluid; at birth the patient failed multiple hearing tests and had small kidneys. What is your diagnosis?
A child with a painless, deformed wrist
Authors: Christopher Mark Peake, Katie Hughes, Andrea Yeo
Journal: BMJ (2018)

A 7 year old boy presented to the emergency department after his mother noticed a painless deformity of his right wrist. The deformity had appeared the day after the child had tripped and fallen on to the wrist while playing at home. He had no known medical problems and was developing well. Specifically, he had experienced no previous injury or pain in his right wrist, although he was brought to the emergency department a few months previously for a minor injury to his right thumb. His father had noted a minor enlargement of the thumb, but the boy had not undergone radiography.

On examination, his right wrist was in radial deviation with prominence of the ulna. There were no areas of focal tenderness. The proximal phalanges of his thumb and index finger were wider in girth than the other fingers, with obvious bony protuberances. He could grasp an object using his fingers and thumb with good strength and no pain. He had a full range of movement of all joints of the hand and at the wrist. There were no skin changes or neurovascular abnormalities.

He was initially seen by the emergency team who took radiographs (fig 1) and referred him to the orthopaedic team for review.



Fig 1 
Anterior-posterior and lateral radiographs of the patient’s right wrist and anterior-posterior radiograph of the right hand. An anterior-posterior radiograph of the left hand was taken for comparison (far right)





### 1. What is the diagnosis?

#### Short answer

The patient presented with a painless wrist deformity and bony lesions in the fingers. The radiographs show multiple, well …
Hospitals in England see deficits grow as wage bills rise and earning capacity falls
Authors: Nigel Hawkes
Journal: BMJ (2018)

NHS hospitals in England are facing ballooning deficits as they struggle to maintain quality of care for growing numbers of patients, show the latest quarterly statistics from NHS Improvement.1 At the end of 2017, hospitals reported a deficit of £1.28bn (€1.45bn; $1.8bn), £365m above the planned level.

The data cover the three months to 31 December, before the winter proper and a severe flu season that generated the highest number of flu related admissions to hospital since 2010-11. The flu peak was reached in January, so next quarter’s data, due to be published on 21 May, may bring worse news.

However, preparations for winter seem to have had some positive effect. Comparing year to year, emergency departments’ performance remained well below target but got no worse: 89.5% of patients were seen within the target of four hours, against 89.6% in the corresponding quarter last year. But December was a poor month, with only 85.1% seen within the target, one …
Number of singlehanded GPs in England has nearly halved since 2002
Authors: Helen Jaques
Journal: BMJ (2013)

The number of singlehanded GPs in England has almost halved over the past decade, figures from the NHS Health and Social Care Information Centre show.1

In 2002 almost a 10th (9.1%) of GP partners were singlehanded providers of general practice, whereas in 2012 only 5.5% of partners were.

The BMA believes that the drop in the number of singlehanded practices could reduce patients’ opportunity for one on one personal care with the same GP on each visit.

Singlehanded GP providers are partners who practise without …