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5. Regional Histopathology and Prostate MRI Positivity: A Secondary Analysis of the PROMIS Trial

Author

Stavrinides, Vasilis, Norris, Joseph M, Karapanagiotis, Solon, Giganti, Francesco, Grey, Alistair, Trahearn, Nick, Freeman, Alex, Haider, Aiman, Carmona Echeverría, Lina María, Bott, Simon RJ, Brown, Louise C, Burns-Cox, Nicholas, Dudderidge, Timothy J, El-Shater Bosaily, Ahmed, Ghei, Maneesh, Henderson, Alastair, Hindley, Richard G, Kaplan, Richard S, Oldroyd, Robert, Parker, Chris, Persad, Raj, Rosario, Derek J, Shergill, Iqbal S, Winkler, Mathias, Kirkham, Alex, Punwani, Shonit, Whitaker, Hayley C, Ahmed, Hashim U, Emberton, Mark, PROMIS Group, Stavrinides, Vasilis [0000-0003-0011-9792], Karapanagiotis, Solon [0000-0003-4460-2073], Giganti, Francesco [0000-0001-5218-6431], Grey, Alistair [0000-0001-6017-8546], Trahearn, Nick [0000-0002-8596-0996], Haider, Aiman [0000-0002-7005-4245], Carmona Echeverría, Lina María [0000-0001-6546-8980], Bott, Simon RJ [0000-0001-7171-8456], Brown, Louise C [0000-0003-2827-6634], Burns-Cox, Nicholas [0000-0002-2332-4804], Dudderidge, Timothy J [0000-0001-6373-3613], El-Shater Bosaily, Ahmed [0000-0003-0586-0897], Henderson, Alastair [0000-0002-3546-1099], Hindley, Richard G [0000-0002-7568-1694], Kaplan, Richard S [0000-0002-0189-8348], Oldroyd, Robert [0000-0002-4969-3544], Parker, Chris [0000-0001-6512-124X], Persad, Raj [0000-0002-9121-0550], Rosario, Derek J [0000-0002-9086-3592], Whitaker, Hayley C [0000-0002-2695-0202], Ahmed, Hashim U [0000-0003-1674-6723], Emberton, Mark [0000-0003-4230-0338], and Apollo - University of Cambridge Repository

Subjects
Male, Prostatic Intraepithelial Neoplasia, Image-Guided Biopsy, Inflammation, Prostate, Humans, Prostatic Neoplasms, Middle Aged, Neoplasm Grading, Magnetic Resonance Imaging
Abstract

Background The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. Purpose To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. Materials and Methods In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3-5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. Results Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9; P < .001) or Gleason score greater than or equal to 4+3 (OR, 8.7; 95% CI: 4.5, 17.0; P < .001). MCCL also determined visibility (OR, 1.24 per millimeter increase; 95% CI: 1.15, 1.33; P < .001), but odds were lower with each prostate volume doubling (OR, 0.7; 95% CI: 0.5, 0.9). In men who were TPM-negative, the presence of PIN increased the odds of zonal visibility (OR, 3.7; 95% CI: 1.5, 9.1; P = .004). Conclusion An incremental relationship between cancer burden and prostate MRI visibility was observed. Prostatic intraepithelial neoplasia contributed to false-positive MRI findings. ClinicalTrials.gov registration no. NCT01292291 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Published
2023

9. ENDGAMES

Author

Shalchi, Zaid, Lightman, Susan L, Pusey, Charles D, Taylor, Simon RJ, and Sedgwick, Philip

Published
2012

12. Contributors

Author

Angus, Brian J, Baker, Adam C, Boyle, James G, Campbell, Harry, Soon Chew, Thean, Clifton, Ian J, Clive, Sally, Clunie, Gavin PR, Clutterbuck, Daniel J, Colvin, Lesley A, Connor, Myles D, Conway, Bryan, Cooper, Nicola, Cracknell, Alison L, Culligan, Dominic J, Dockrell, David H, Ellames, Deborah AB, Fallon, Marie, Gibb, Fraser W, Gordon-Walker, Timothy T, Grubb, Neil R, Hunt, David PJ, Ibbotson, Sally H, Jenks, Sara J, Johnston, Sarah L, Lawrie, Stephen M, Lean, Michael EJ, Maartens, Gary, Mackillop, Lucy H, MacMahon, Michael J, Mann, Rebecca J, Manson, Lynn M, Mather, Amanda, Maxwell, Simon RJ, McAllister, David A, Miller-Hodges, Eve, Neuberger, Francesca EM, Newby, David E, Newell-Price, John DC, Olson, John A, Petrie, John R, Phelan, Paul J, Quinn, Terence J, Ralston, Stuart H, Rej, Anupam, Sanders, David S, Sandoe, Jonathan AT, Shand, Alan G, Stares, Mark, Steel, Robby M, Stewart, Grant D, Sullivan, David R, Sundar, Shyam, Tallentire, Victoria R, Tatton-Brown, Katrina, Thomas, Simon HL, Watson, Henry G, White, Julian, Whiteley, William, Williams, Michael J, and Woodfield, Rebecca

Published
2023
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20. Valacyclovir in the treatment of acute retinal necrosis

Author

Taylor Simon RJ, Hamilton Robin, Hooper Claire Y, Joshi Lavnish, Morarji Jiten, Gupta Nitin, and Lightman Sue L

Subjects
Acute retinal necrosis, Herpetic retinitis, Acyclovir, Valacyclovir, Ophthalmology, RE1-994
Abstract

Abstract Background To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN). Methods This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline) and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA) at final follow-up, retinal detachment and development of recurrent or second eye disease. Results Retinitis resolved in ten of ten (100%) affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60%) of eyes. 3/10 eyes (30%) developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks). Conclusions Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovir.

Published
2012
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24. Anti-oxidant therapy: does it have a role in the treatment of human disease?

Author

Simon Rj Maxwell

Subjects
Pharmacology, Pathology, medicine.medical_specialty, Vascular disease, business.industry, Inflammation, General Medicine, Anti oxidant, medicine.disease, Bioinformatics, medicine.disease_cause, Pathogenesis, Human disease, Diabetes mellitus, medicine, Pharmacology (medical), medicine.symptom, business, Reperfusion injury, Oxidative stress
Abstract

Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. Natural anti-oxidant defences have also been found to be defective in many of the same diseases. Many researchers have concluded that, if the imbalance between the oxidative stresses and anti-oxidant defence can be corrected by supplementing natural anti-oxidant defences, it may be possible to prevent or retard disease progression. Potential anti-oxidant therapies include natural anti-oxidant enzymes and vitamins or synthetic agents with anti-oxidant activity. Diseases where anti-oxidant therapy may be beneficial can be divided into those involving acute intervention, such as reperfusion injury or inflammation, and those involving chronic preventative therapy, such as atherosclerosis, carcinogenesis and diabetic vascular disease. The pharmaceutical considerations are different in each case. The principles guiding the development, use and assessment of anti-oxidant therapies are discussed in this review.

Published
1997
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25. Contributors

Author

Angus, Brian J, Anstee, Quentin M, Burnett, Leslie, Byers, Mark, Campbell, Harry, Clunie, Gavin PR, Colvin, Lesley A, Conway, Bryan, Cooper, Nicola, Cracknell, Alison L, Culligan, Dominic J, Dark, Graham G, Davenport, Richard J, Dockrell, David H, El-Omar, Emad, Fallon, Marie, FitzPatrick, David R, Grubb, Neil R, Ibbotson, Sally H, Innes, J Alastair, Jenks, Sara J, Johnston, Sarah L, Jones, David EJ, Langhorne, Peter, Lawrie, Stephen M, Leach, John Paul, Maartens, Gary, Mackillop, Lucy, MacMahon, Michael J, Mann, Rebecca, Manson, Lynn M, Marshall, Sara E, Mather, Amanda, Maxwell, Simon RJ, McAllister, David A, McCrimmon, Rory J, McLean, Mairi H, Neuberger, Francesca EM, Newby, David E, Newell-Price, John DC, Olson, John, Pearson, Ewan R, Phelan, Paul J, Ralston, Stuart H, Reid, Peter T, Sandoe, Jonathan AT, Scott, Gordon R, Shand, Alan G, Steel, Robby M, Stewart, Grant D, Stewart, Peter, Strachan, Mark WJ, Sullivan, David R, Sundar, Shyam, Tallentire, Victoria R, Tatton-Brown, Katrina, Thomas, Simon HL, Watson, Henry G, White, Julian, Wilding, John PH, and Witham, Miles D

Published
2018
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30. Birdshot uveitis: current and emerging treatment options

Author

Menezo,Victor, Taylor,Simon RJ, Menezo,Victor, and Taylor,Simon RJ

Abstract

Victor Menezo,1,2 Simon RJ Taylor3,4 1Institut Catala de Retina, Barcelona, Spain; 2Department of Ophthalmology, Provincial Hospital Consortium Castellon, Castello, Spain; 3Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK; 4Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK Abstract: Birdshot chorioretinopathy is a relatively uncommon subtype of idiopathic posterior uveitis with distinct clinical characteristics and a strong genetic association with the Human Leukocyte Antigen (HLA)-A29 allele. The diagnosis remains clinical and is based on the presence of typical clinical features, including multiple, distinctive, hypopigmented choroidal lesions throughout the fundus. The long-term visual prognosis of this disorder, however, remains guarded – central visual acuity can be preserved until late in the disease and it is not uncommon for patients to receive inadequate immunosuppressive treatment, leading to a poor long-term outcome in which peripheral retinal damage eventually leads to visual deterioration. Birdshot chorioretinopathy has proven a particularly attractive area of study within the field of uveitis, as it is a relatively easily defined disease with an associated human leukocyte antigen haplotype. Despite this, however, the immune mechanisms involved in its pathogenesis remain unclear, and some patients continue to lose retinal function despite therapy with corticosteroids and conventional immunosuppressive agents. Laboratory research continues to investigate the underlying mechanisms of disease, and clinical research is now being driven to improve the phenotyping and monitoring of this condition as, in the era of so-called personalized medicine, it is becoming increasingly important to identify patients at risk of visual loss early so that they can be treated more aggressively with targeted therapies such as the newer biological agents. This approach requires the formation of collaborative groups, as the

Published
2013

33. Oxygen therapy in acute medical care: the potential dangers of hyperoxia need to be recognised. (Editorials)

Author

Thomson, Alastair J., Webb, David J., Maxwell, Simon RJ, and Grant, Ian S.

Subjects
Oxygen therapy -- Dosage and administration, Oximetry, Health, Dosage and administration
Abstract

Oxygen is cheap, widely available, and used in a range of settings and conditions to relieve or prevent tissue hypoxia. Since its discovery by Scheele and Priestley in the 1770s, [...]

Published
2002

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