tbuckley/cabot-search huggingface dataset:
GMC is causing anxiety and distress by treating health problems like conduct issues, researchers say
Authors: Tom Moberly
Journal: BMJ (2014)

The General Medical Council (GMC) should create a separate system for assessing unwell doctors, because its practice of treating health problems in the same way as conduct issues is causing anxiety and distress, researchers have said.

Doctors who have been away from work with health problems often find the GMC’s processes “anxiety provoking” and “distressing”, said a team led by Samantha Brooks, a psychologist at the Institute of Psychiatry at King’s College, London.1 The GMC’s process is seen as “long and drawn out,” the legal wording of letters is perceived as “daunting,” and the “accusatory” tone of correspondence makes doctors uncomfortable, the researchers added.

The GMC’s “conflation” of ill health with misconduct “seems at …
Virtual Coronary Intervention
Authors: Rebecca C. Gosling, Paul D. Morris, Daniel A. Silva Soto, Patricia V. Lawford, D. Rodney Hose, Julian P. Gunn
Journal: JACC. Cardiovascular imaging (2018)

This study sought to assess the ability of a novel virtual coronary intervention (VCI) tool based on invasive angiography to predict the patient's physiological response to stenting.Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is associated with improved clinical and economic outcomes compared with angiographic guidance alone. Virtual (v)FFR can be calculated based upon a 3-dimensional (3D) reconstruction of the coronary anatomy from the angiogram, using computational fluid dynamics (CFD) modeling. This technology can be used to perform virtual stenting, with a predicted post-PCI FFR, and the prospect of optimized treatment planning.Patients undergoing elective PCI had pressure-wire-based FFR measurements pre- and post-PCI. A 3D reconstruction of the diseased artery was generated from the angiogram and imported into the VIRTUheart workflow, without the need for any invasive physiological measurements. VCI was performed using a radius correction tool replicating the dimensions of the stent deployed during PCI. Virtual FFR (vFFR) was calculated pre- and post-VCI, using CFD analysis. vFFR pre- and post-VCI were compared with measured (m)FFR pre- and post-PCI, respectively.Fifty-four patients and 59 vessels underwent PCI. The mFFR and vFFR pre-PCI were 0.66 ± 0.14 and 0.68 ± 0.13, respectively. Pre-PCI vFFR deviated from mFFR by ±0.05 (mean Δ = -0.02; SD = 0.07). The mean mFFR and vFFR post-PCI/VCI were 0.90 ± 0.05 and 0.92 ± 0.05, respectively. Post-VCI vFFR deviated from post-PCI mFFR by ±0.02 (mean Δ = -0.01; SD = 0.03). Mean CFD processing time was 95 s per case.The authors have developed a novel VCI tool, based upon the angiogram, that predicts the physiological response to stenting with a high degree of accuracy.
Serum exosomes can restore cellular function <i>in vitro</i> and be used for diagnosis in dysferlinopathy
Authors: Xue Dong, Xianjun Gao, Yi Dai, Ning Ran, HaiFang Yin
Journal: Theranostics (2018)

Purpose: It is challenging to deliver the full-length dysferlin gene or protein to restore cellular functions of dysferlin-deficient (DYSF -/-) myofibres in dysferlinopathy, a disease caused by the absence of dysferlin, which is currently without effective treatment.Exosomes, efficient membranous nanoscale carriers of biological cargoes, could be useful.Experimental design: Myotube-and human serum-derived exosomes were investigated for their capabilities of restoring dysferlin protein and cellular functions in murine and human DYSF -/-cells.Moreover, dysferlinopathic patient serum-and urine-derived exosomes were assessed for their abilities as diagnostic tools for dysferlinopathy.Results: Here we show that exosomes from dysferlin-expressing myotubes carry abundant dysferlin and enable transfer of full-length dysferlin protein to DYSF -/-myotubes.Exogenous dysferlin correctly localizes on DYSF -/-myotube membranes, enabling membrane resealing in response to injury.Human serum exosomes also carry dysferlin protein and improve membrane repair capabilities of human DYSF -/-myotubes irrespective of mutations.Lack of dysferlin in dysferlinopathic patient serum and urine exosomes enables differentiation between healthy controls and dysferlinopathic patients.Conclusions: Our findings provide evidence that exosomes are efficient carriers of dysferlin and can be employed for the treatment and non-invasive diagnosis of dysferlinopathy.
Rheumatoid arthritis indicators proposed for QOF
Authors: Caroline White
Journal: BMJ (2012)

The National Institute for Health and Clinical Excellence (NICE) has proposed several new rheumatoid arthritis indicators for inclusion in the Quality and Outcomes Framework (QOF).

If the indicators are accepted by the BMA’s General Practitioners Committee and NHS Employers later this year, 2013-14 will be the first time that rheumatoid arthritis has made it into the incentive scheme for GPs.

The indicators …
Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats
Authors: Rui Li, Yiyang Li, Yanqing Wu, Yingzheng Zhao, Huanwen Chen, Yuan Yuan, Ke Xu, Hongyu Zhang, Yingfeng Lu, Jian Wang, Xiaokun Li, Xiaofeng Jia, Jian Xiao
Journal: Biomaterials (2018)
Tumor-normal sequencing to reveal frequency of false positive error rates with tumor-only sequencing in GI cancers and with RNA sequencing as a new standard of precision molecular profiling.
Authors: Chad Garner, Sandip Reddy, John Z Sanborn, Stephen Charles Benz, Patrick Soon-Shiong, Shahrooz Rabizadeh
Journal: Journal of Clinical Oncology (2018)

224 Background: Tumor-only sequencing to identify somatic tumor genomic variants increases the risk of mistakenly identifying germline mutations as somatically derived driver mutations. Simultaneous bioinformatics analysis of both normal germline and the tumor genome with RNA analysis is necessary for precise identification of molecular targets for cancer therapy. The objective of this study was to compare the accuracy and precision of tumor somatic SNV calling with a 45-gene GI cancer molecular actionability panel, analyzing tumor tissue alone versus analyzing tumor DNA with normal germline DNA and tumor RNA. Methods: The study included 204 cancer patients with 11 GI cancer types with whole genome sequencing of tumor and normal genomes. True positive and false positive rates were measured for single nucleotide variants (SNVs). RNA sequencing was available for 139 patients to determine SNVs expressed in messenger RNA. SNVs were identified using well-established and published bioinformatics methods. False positive results were SNVs identified as being somatic origin that were of germline origin. Results: 92% SNVs identified from sequencing tumor genomes alone were of germline origin (false positives) rather than true somatic mutations. Filtering the SNVs using a public database with reported population allele frequencies &lt; 0.001 still resulted in a false positive rate of 41%. Furthermore, 71% of GI cancer patients had at least one false positive SNV after filtering. RNA analysis showed 10% of true somatic variants were not expressed and 17% of patients had at least one true somatic variant that was not expressed. Conclusions: Simultaneous sequencing and analysis of both normal germline and tumor genomes is necessary for accurate identification of molecular targets. Analysis of tumor genome alone results in a high false positive rate. Higher precision is achieved with simultaneous tumor-normal DNA and RNA sequencing analysis. Treatment decisions based on tumor-only DNA analysis or in the absence of RNA analysis can result in administration of ineffective therapies and increasing risk of negative drug-related side effects.
NON-ALCOHOLIC FATTY LIVER DISEASE IS ASSOCIATED WITH ONSET OF ATRIAL FIBRILLATION AT A YOUNGER AGE: A NATIONWIDE STUDY
Authors: Farid Gholitabar, Shawn Lee, May Bakir, Seyed Hamed Hosseini Dehkordi, Syed Ahsan, Alejandro Lemor, Davendra Mehta
Journal: Journal of the American College of Cardiology (2018)
GPs must inform DVLA if patients drive against medical advice, says GMC
Authors: Abi Rimmer
Journal: BMJ (2015)

GPs must inform the Driver and Vehicle Licensing Agency (DVLA) if a patient continues to drive against medical advice, the General Medical Council has said.

New draft guidance from the GMC emphasised a doctor’s duty to disclose information to the DVLA, or DVA in Northern Ireland, when patients failed to do so themselves.1

It said that, if a patient posed a risk of serious harm …
Tau Kinetics in Neurons and the Human Central Nervous System
Authors: Chihiro Sato, Nicolas R. Barthélemy, Kwasi G. Mawuenyega, Bruce W. Patterson, Brian A. Gordon, Jennifer Jockel-Balsarotti, Melissa Sullivan, Matthew J. Crisp, Tom Kasten, Kristopher M. Kirmess, Nicholas M. Kanaan, Kevin E. Yarasheski, Alaina Baker-Nigh, Tammie L.S. Benzinger, Timothy M. Miller, Celeste M. Karch, Randall J. Bateman
Journal: Neuron (2018)
Anaplastic Thyroid Cancer With Extensive Skeletal Muscle Metastases on 18F-FDG PET/CT
Authors: Ilana R. Yurkiewicz, Kristen N. Ganjoo, Andrei Iagaru
Journal: Clinical Nuclear Medicine (2018)

A 61-year-old woman with newly diagnosed anaplastic thyroid cancer and known metastases to the brain, lungs, and adrenal glands complained of groin muscle pain. F-FDG PET/CT was performed to assess for extent of disease and showed extensive hypermetabolic lesions throughout the skeletal musculature concerning for metastatic disease. As this would be a very rare presentation for anaplastic thyroid carcinoma, a biopsy of the left gluteal muscle was conducted. Pathology demonstrated anaplastic thyroid carcinoma, metastatic to skeletal muscle.
Is it possible for overseas doctors to work in the United Kingdom without passing the PLAB exam?
Authors: Jo Constable
Journal: BMJ (2004)

<i>Got 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 (www.bmjcareers.com/advicezone) 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.</i>
CheckMate 648: A randomized phase 3 study of nivolumab plus ipilimumab or nivolumab combined with fluorouracil plus cisplatin versus fluorouracil plus cisplatin in patients with unresectable advanced, recurrent, or metastatic previously untreated esophageal squamous cell carcinoma.
Authors: Jaffer A. Ajani, Ken Kato, Yuichiro Doki, Ian Chau, Ioannis Xynos, Agnes Balogh, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2018)

TPS193 Background: Esophageal cancer (EC) is the sixth most common cause of cancer-related death worldwide, with a 5-y survival rate of 5%–8% in pts with metastatic disease. First–line platinum-based doublet chemotherapy (CTX) provides a modest survival benefit in pts with metastatic squamous cell EC (mESCC), with a median OS of 7.6 months. Over 40% of pts with EC have PD-L1 + tumors, which are associated with worse OS outcomes. Nivolumab (NIVO), an anti–PD-1 mAb, demonstrated efficacy and a manageable safety profile in pts with ESCC. In the phase 2 ATTRACTION-1 trial, NIVO 3 mg/kg produced an ORR of 17% and median OS of 10.8 months in heavily pretreated pts with ESCC (Kudo T et al Lancet Oncol 2017). NIVO + ipilimumab (IPI) yielded enhanced responses with a manageable safety profile in multiple tumor types. Similarly, NIVO + platinum-based CTX resulted in encouraging clinical activity and an acceptable safety profile in pts with metastatic gastric cancer and SCC NSCLC. This randomized phase 3 study will evaluate the efficacy and safety of NIVO + IPI or NIVO + fluorouracil (5-FU)/cisplatin (Cis) vs 5-FU/Cis as first-line treatment (Tx) in pts with advanced (adv) or mESCC (CheckMate 648; NCT03143153). Methods: 939 pts aged ≥ 18 y with histologically confirmed unresectable advanced, recurrent or mESCC, not amenable to curative approaches, and no prior systemic therapy for advanced/metastatic disease, with adequate organ function and ECOG PS 0 or 1 will be randomized 1:1:1 to NIVO + IPI, NIVO + 5-FU/Cis or 5-FU/Cis. Pts with autoimmune diseases, serious or uncontrolled medical disorders; active infections or positive for HIV, AIDS, or hepatitis B/C, indicating acute or chronic infection and/or detectable virus; and previous Tx with other therapy targeting T-cell co-stimulation or immune checkpoint pathways are excluded. Primary endpoints are OS and PFS by central assessment in pts with a PD-L1 + tumor (defined as PD-L1 expression on ≥ 1% of tumor cells). Secondary endpoints include ORR, PFS, and OS in all pts, as well as ORR in pts with PD-L1 + tumors. Clinical trial information: NCT03143153.
How does one become a ship's doctor? What are the minimum requirements and what would be recommended?
Authors: Alon Duby
Journal: BMJ (2005)

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>
Clear Cell Sarcoma of the Tongue on MRI and PET/CT
Authors: Mickael Tordjman, Matthieu Dubois, Maxime de Malherbe, Yves Denoux, Quentin Gillebert
Journal: Clinical Nuclear Medicine (2018)

F-FDG PET/CT and MRI were performed in a 44-year-old woman to characterize a mass of the anterior tongue. MR images showed a voluminous mass, well circumscribed and enhanced heterogeneously after gadolinium chelates injection. There was an intense uptake on PET/CT. Pathological examination and molecular analysis revealed the diagnosis of clear cell sarcoma of the tongue. We present a case of clear cell sarcoma of the tongue, which includes imaging features. It is an extremely rare tumor, with only 3 cases previously reported in the literature.
Sixty seconds on . . . OxyContin
Authors: Anne Gulland
Journal: BMJ (2018)

No, that’s oxytocin, you dope. This is the time released formulation of the semi-synthetic opioid oxycodone, marketed by Purdue Pharma, which stands accused of unleashing the US’s opioid epidemic. That’s the one that’s been estimated to have cost the US economy $504bn (£361bn; €410bn) in 2015 and been involved in 42 249 deaths in the US in 2016.1

Purdue is also targeted in more than 200 lawsuits for fraudulent marketing of its pill. And it has been named in a Senate report …
Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial
Authors: I. Sobhani, E. Itti, A. Luciani, I. Baumgaertner, R. Layese, T. André, M. Ducreux, J.-M. Gornet, G. Goujon, T. Aparicio, J. Taieb, J.-B. Bachet, F. Hemery, A. Retbi, M. Mons, R. Flicoteaux, B. Rhein, S. Baron, I. Cherrak, P. Rufat, P. Le Corvoisier, N. de’Angelis, P.-A. Natella, H. Maoulida, C. Tournigand, I. Durand Zaleski, S. Bastuji-Garin
Journal: Annals of Oncology (2018)

Background[18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs.Patients and methodsIn this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan–Meier method, log-rank test, and Cox models. Direct costs were compared.ResultsOf the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80–1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8–2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3–20) versus 14.3 (7.3–27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13 €, P < 0.033).Conclusion18FDG-PET/CT, when added every 6 months, increased costs without decreasing treatment failure rates in patients in remission of CRC. The control group had very close follow-up, and any additional improvement (if present) would be small and hard to detect.ClinicalTrials.gov identifierNCT00624260
SUDDEN CARDIAC DEATH AND ABORTED SUDDEN CARDIAC DEATH IN PATIENTS WITH ANOMALOUS AORTIC ORIGIN OF A CORONARY ARTERY (AAOCA) FROM THE INAPPROPRIATE SINUS OF VALSALVA: A SYSTEMATIC REVIEW OF THE LITERATURE
Authors: Hunain Shiwani, Julie Brothers, Todd Villines, Richard Liberthson, Ron Blankstein, Michael Cheezum
Journal: Journal of the American College of Cardiology (2018)
2-Hydroxyglutarate-Mediated Autophagy of the Endoplasmic Reticulum Leads to an Unusual Downregulation of Phospholipid Biosynthesis in Mutant IDH1 Gliomas
Authors: Pavithra Viswanath, Marina Radoul, Jose Luis Izquierdo-Garcia, Wei Qiang Ong, Hema Artee Luchman, J. Gregory Cairncross, Bo Huang, Russell O. Pieper, Joanna J. Phillips, Sabrina M. Ronen
Journal: Cancer Research (2018)

Abstract Tumor metabolism is reprogrammed to meet the demands of proliferating cancer cells. In particular, cancer cells upregulate synthesis of the membrane phospholipids phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdE) in order to allow for rapid membrane turnover. Nonetheless, we show here that, in mutant isocitrate dehydrogenase 1 (IDHmut) gliomas, which produce the oncometabolite 2-hydroxyglutarate (2-HG), PtdCho and PtdE biosynthesis is downregulated and results in lower levels of both phospholipids when compared with wild-type IDH1 cells. 2-HG inhibited collagen-4-prolyl hydroxylase activity, leading to accumulation of misfolded procollagen-IV in the endoplasmic reticulum (ER) of both genetically engineered and patient-derived IDHmut glioma models. The resulting ER stress triggered increased expression of FAM134b, which mediated autophagic degradation of the ER (ER-phagy) and a reduction in the ER area. Because the ER is the site of phospholipid synthesis, ER-phagy led to reduced PtdCho and PtdE biosynthesis. Inhibition of ER-phagy via pharmacological or molecular approaches restored phospholipid biosynthesis in IDHmut glioma cells, triggered apoptotic cell death, inhibited tumor growth, and prolonged the survival of orthotopic IDHmut glioma-bearing mice, pointing to a potential therapeutic opportunity. Glioma patient biopsies also exhibited increased ER-phagy and downregulation of PtdCho and PtdE levels in IDHmut samples compared with wild-type, clinically validating our observations. Collectively, this study provides detailed and clinically relevant insights into the functional link between oncometabolite-driven ER-phagy and phospholipid biosynthesis in IDHmut gliomas. Significance: Downregulation of phospholipid biosynthesis via ER-phagy is essential for proliferation and clonogenicity of mutant IDH1 gliomas, a finding with immediate therapeutic implications. Cancer Res; 78(9); 2290–304. ©2018 AACR.
Combined pathologic‐genomic algorithm for early-stage breast cancer improves cost-effective use of the 21-gene recurrence score assay
Authors: M.M. Gage, W.C. Mylander, M. Rosman, T. Fujii, F. Le Du, A. Raghavendra, A.K. Sinha, J.R. Espinosa Fernandez, A. James, N.T. Ueno, L. Tafra, R.S. Jackson
Journal: Annals of Oncology (2018)

<h2>Abstract</h2><h3>Background</h3> The 21-gene recurrence score (RS) (Onco<i>type</i> DX®; Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologic‐genomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients. <h3>Patients and methods</h3> A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan–Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model's risk groups. <h3>Results</h3> A total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, <i>n=</i>322) and the RS<18 low-risk group (3.4%, <i>n=</i>703), as well as between the AAMC high-risk group (22.8%, <i>n=</i>230) and the RS>30 high-risk group (23.0%, <i>n=</i>141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (<i>n=</i>739) and 24.2% for the high-risk group (<i>n=</i>272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing. <h3>Conclusions</h3> AAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk.
Chronic exertional compartment syndrome of the deep posterior lower leg
Authors: Michiel B Winkes, Marc R Scheltinga
Journal: British Journal of Sports Medicine (2018)

The general aim was to study several aspects of diagnosis and treatment of chronic exertional compartment syndrome of the deep posterior lower leg (dp-CECS) and to identify possible causes for poor outcome after surgery.1 First, we performed a review of current practice regarding dp-CECS. Second, we sought to establish a relationship between elevated intracompartmental muscle pressures (being the gold diagnostic standard of CECS at present) and postoperative outcome.2 Third, the accuracy of catheter placement for intracompartmental pressure measurements was studied.3 Finally, patients with isolated dp-CECS were prospectively studied 3 and 12 months after surgery whereas reasons for an unsuccessful response were identified.4 

Up to 27 per cent of healthy individuals presenting with exertional leg pain may suffer from CECS. Roughly half harbour a dp-CECS. Symptoms are often so disabling that sports activities are impossible. In …