WUTH publication: Spontaneous pneumomediastinum and pneumopericardium in a young healthy adult with plans for air travel

Citation: Clinical Case Reports. 2020, 8(12), 3075-78
Author: Joseph Winterton, Simon Biart 

Abstract: Although rare, pneumomediastinum and pneumopericardium should be considered in patients presenting with sudden onset post-tussive chest discomfort.

Keywords: acute medicine; cardiothoracic surgery; respiratory medicine.

Link to PubMed record

WUTH publication: Antibiotic prophylaxis during dental implant placement in the UK

Citation: British Dental Journal. 2020, 229(12), 787-92. Epub 2020 Dec 18

Author: Robert G M Williams
Abstract: Background Antimicrobial resistance is a growing concern globally. It has previously been demonstrated that antibiotic prescribing for dental implants within the UK is varied with an apparent lack of guidance. This study aimed to establish current use of antibiotic prophylaxis during dental implant placements in the UK.Method An anonymous validated online questionnaire was distributed to members of the BAOS, BSSPD, BSP, ADI and ITI. Data were then collated and analysed.Results Two hundred and twenty-nine responses were received during April-July 2018. Fifty-five percent of dentists routinely prescribed antibiotics during implant placements. One-third did sometimes, but not routinely. Thirteen percent never prescribed. Reported protocols contained 61 different drug/dose combinations given over 124 different regimens. Those who prescribed routinely had significantly higher levels of training/qualification (P = 0.008), placed more implants (P = 0.014) and undertook more complex placements (P = 0.002) than non-prescribers. Seventy-three percent believed antibiotics decrease post-operative infection. One in ten felt they gave no benefit. Half believed they decrease implant failure. Over 90% would like national guidelines.Conclusion Significant variance in practice is clear. Almost half of practitioners did not routinely prescribe. Those who did were significantly more experienced, highly trained and did more complex placements. There was a difference between practitioners' perceived benefits of antibiotic prophylaxis and the evidence in the literature. There was a great desire for clearer guidance.

Link to PubMed record

CCC publication: ESTRO ACROP guideline for target volume delineation of skull base tumors

Citation: Radiotherapy and Oncology. 2021, 156, 80-94. (2020, S0167-8140(20), 31179-8)

Author: Stephanie E Combs, Brigitta G Baumert, Martin Bendszus, Alessandro Bozzao, Michael Brada, Laura Fariselli, Alba Fiorentino, Ute Ganswindt, Anca L Grosu, Frank L Lagerwaard, Maximilian Niyazi, Tufve Nyholm, Ian Paddick, Damien Charles Weber, Claus Belka, Giuseppe Minniti 

Abstract: Background and purpose: For skull base tumors, target definition is the key to safe high-dose treatments because surrounding normal tissues are very sensitive to radiation. In the present work we established a joint ESTRO ACROP guideline for the target volume definition of skull base tumors.

Material and methods: A comprehensive literature search was conducted in PubMed using various combinations of the following medical subjects headings (MeSH) and free-text words: "radiation therapy" or "stereotactic radiosurgery" or "proton therapy" or "particle beam therapy" and "skull base neoplasms" "pituitary neoplasms", "meningioma", "craniopharyngioma", "chordoma", "chondrosarcoma", "acoustic neuroma/vestibular schwannoma", "organs at risk", "gross tumor volume", "clinical tumor volume", "planning tumor volume", "target volume", "target delineation", "dose constraints". The ACROP committee identified sixteen European experts in close interaction with the ESTRO clinical committee who analyzed and discussed the body of evidence concerning target delineation.

Results: All experts agree that magnetic resonance (MR) images with high three-dimensional spatial accuracy and tissue-contrast definition, both T2-weighted and volumetric T1-weighted sequences, are required to improve target delineation. In detail, several key issues were identified and discussed: i) radiation techniques and immobilization, ii) imaging techniques and target delineation, and iii) technical aspects of radiation treatments including planning techniques and dose-fractionation schedules. Specific target delineation issues with regard to different skull base tumors, including pituitary adenomas, meningiomas, craniopharyngiomas, acoustic neuromas, chordomas and chondrosarcomas are presented.

Conclusions: This ESTRO ACROP guideline achieved detailed recommendations on target volume definition for skull base tumors, as well as comprehensive advice about imaging modalities and radiation techniques.

Keywords: EORTC; RTOG; chondrosarcoma; chordoma; consensus; craniopharyngioma; meningioma; pituitary adenoma; radiotherapy; skull base target volume; target delineation; vestibular schwannoma.

Link to PubMed record

CCC publication: A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM)

Citation: Annals of Oncology. 2020, 31(Sup7), S1442-3

Author: J.J. Sacco, R. Carvajal, M.O. Butler, A.N. Shoushtari, J.C. Hassel, A. Ikeguchi, L. Hernandez-Aya, P. Nathan, O. Hamid, J.M. Piulats Rodriguez, M. Rioth, D.B. Johnson, J.J. Luke, E. Espinosa, S. Leyvraz, H.M. Goodall, C. Holland, S. Abdullah, T. Sato,

CCC publication: Management of Newly-diagnosed Metastatic Hormone-sensitive Prostate Cancer: a Survey of UK Uro-oncologists

Citation: International Journal of Clinical Practice. 2020 Nov 30; e13874. Online ahead of print.

Author: Amit Bahl, Simon Crabb, Dan Ford, Rob Jones, Zaf Malik, Danish Mazhar, Joe O'Sullivan, Heather Payne

Abstract: Aim: To explore the practice and views of uro-oncologists in the UK regarding their use of chemotherapy and androgen receptor-targeted agents (ARTAs) in patients with newly-diagnosed metastatic hormone-sensitive prostate cancer (mHSPC).

Methods: An expert-devised paper or online questionnaire was completed by members of the British Uro-oncology Group.

Results: All respondents stated that they would offer patients with newly-diagnosed mHSPC docetaxel and androgen deprivation therapy (ADT) if they were sufficiently fit to receive chemotherapy (this was the only option available at the time of the survey); 64% would strongly recommend docetaxel for those with high-volume metastatic disease and 31% for those with low-volume disease. Hypothetically, if both docetaxel and ARTAs were available in the UK for mHSPC, almost 65% of respondents would recommend an ARTA with ADT to these patients in at least one-half of all cases, with the strongest recommendations to patients with high-risk disease. Imaging for response was conducted according to suspicion of disease progression, regardless of treatment, with the minority of clinicians recommending routine imaging. If a choice of therapy was available, docetaxel would be more likely to be offered to patients with liver or lung metastases, and ARTAs to patients with bone or lymph node only metastases. Almost all respondents would offer local radiotherapy to the primary tumour in patients with low-volume disease.

Conclusion: All the UK uro-oncologists those surveyed stated that they would offer docetaxel in combination with ADT to all newly-diagnosed patients with mHSPC if fit enough for chemotherapy. ARTAs would be offered to many patients if available, especially those with high-risk disease or those unfit to receive chemotherapy. Scanning was typically conducted following treatment only at suspicion of disease progression.

Keywords: abiraterone; apalutamide; docetaxel; enzalutamide; metastatic hormone-sensitive prostate cancer.

Link to PubMed record

CCC publication: The E3 Ubiquitin Ligase NEDD4L Targets OGG1 for Ubiquitylation and Modulates the Cellular DNA Damage Response

Citation: Frontiers in cell and developmental biology. 2020, eCollection 2020

Author: Jonathan R Hughes, Jason L Parsons 

Abstract: 8-Oxoguanine DNA glycosylase (OGG1) is the major cellular enzyme required for the excision of 8-oxoguanine DNA base lesions in DNA through the base excision repair (BER) pathway, and therefore plays a major role in suppressing mutagenesis and in controlling genome stability. However, the mechanism of regulation of cellular OGG1 protein, particularly in response to oxidative stress, is unclear. We have purified the major E3 ubiquitin ligase responsible for OGG1 ubiquitylation from human cell extracts, and identify this as E3 ubiquitin-protein ligase NEDD4-like (NEDD4L). We demonstrate that recombinant NEDD4L stimulates ubiquitylation of OGG1 in vitro, particularly on lysine 341, and that NEDD4L and OGG1 interact in U2OS cells. Depletion of NEDD4L in U2OS cells has no impact on the stability and steady-state protein levels of OGG1, however, OGG1 stability is enhanced in response to oxidative stress induced by ionizing radiation. Furthermore, ubiquitylation of OGG1 by NEDD4L in vitro inhibits its DNA glycosylase/lyase activity. As a consequence of prolonged OGG1 stability and increased excision activity in the absence of NEDD4L, cells display increased DNA repair capacity but conversely that this decreases cell survival post-irradiation. This effect can be reproduced following OGG1 overexpression, suggesting that dysregulation of OGG1 increases the formation of lethal intermediate DNA lesions. Our study therefore highlights the importance of balancing OGG1 protein levels and BER capacity in maintaining genome stability.

Keywords: DNA damage; DNA repair; NEDD4L; OGG1; ubiquitin.

 

Link to PubMed record

CCC publication: Optimisation of Urine Sample Preparation for Headspace-Solid Phase Microextraction Gas Chromatography-Mass Spectrometry: Altering Sample pH, Sulphuric Acid Concentration and Phase Ratio

Citation: Metabolites. 2020, 10(12), 1-17. [2020, 10(12), E482]

Author: Prashant Aggarwal, James Baker, Mark T Boyd, Séamus Coyle, Chris Probert, Elinor A Chapman

Abstract: Headspace-solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) can be used to measure volatile organic compounds (VOCs) in human urine. However, there is no widely adopted standardised protocol for the preparation of urine samples for analysis resulting in an inability to compare studies reliably between laboratories. This paper investigated the effect of altering urine sample pH, volume, and vial size for optimising detection of VOCs when using HS-SPME-GC-MS. This is the first, direct comparison of H2SO4, HCl, and NaOH as treatment techniques prior to HS-SPME-GC-MS analysis. Altering urine sample pH indicates that H2SO4 is more effective at optimising detection of VOCs than HCl or NaOH. H2SO4 resulted in a significantly larger mean number of VOCs being identified per sample (on average, 33.5 VOCs to 24.3 in HCl or 12.2 in NaOH treated urine) and more unique VOCs, produced a more diverse range of classes of VOCs, and led to less HS-SPME-GC-MS degradation. We propose that adding 0.2 mL of 2.5 M H2SO4 to 1 mL of urine within a 10 mL headspace vial is the optimal sample preparation prior to HS-SPME-GC-MS analysis. We hope the use of our optimised method for urinary HS-SPME-GC-MS analysis will enhance our understanding of human disease and bolster metabolic biomarker identification.

Keywords: H2SO4; HCl; HS-SPME-GC-MS; NaOH; VOCs; hydrochloric acid; sodium hydroxide; vials; volatile organic compounds.

Link to PubMed record