"Textural analysis of multiparametric MRI detects transition zone prostate cancer"

OBJECTIVES: To evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour. METHODS: Sixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had 'significant' TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis. RESULTS: ADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83). CONCLUSION: Textural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion. KEY POINTS: MR textural features of prostate transition zone may discriminate significant prostatic cancer; Transition zone (TZ) containing significant tumour demonstrates a less peaked ADC histogram; TZ containing significant tumour reveals higher post-contrast T1-weighted homogeneity; The utility of MR texture analysis in prostate cancer merits further investigation

‘Video Replay: Families, films and fantasy’ as a transformational text: Commentary on Valerie Walkerdine's ‘Video Replay’.

In this commentary I explore the significance of Valerie Walkerdine's paper ‘Video Replay: Families, Films and Fantasy’. I review its impact in 1986 and then discuss how some of its ideas about subjectivity and popular culture – specifically film - can be developed in the contemporary context. A recurring fantasy of Rocky II and its reception is that of social and psychological transformation. I address this theme by drawing on the work of Christopher Bollas to argue that Walkerdine's psychosocial analysis continues to facilitate, across a range of contexts, some of the transformational processes described in her article

Cutaneous lesions of the nose

Skin diseases on the nose are seen in a variety of medical disciplines. Dermatologists, otorhinolaryngologists, general practitioners and general plastic and dermatologic surgeons are regularly consulted regarding cutaneous lesions on the nose. This article is the second part of a review series dealing with cutaneous lesions on the head and face, which are frequently seen in daily practice by a dermatologic surgeon. In this review, we focus on those skin diseases on the nose where surgery or laser therapy is considered a possible treatment option or that can be surgically evaluated

Role and regulation of MKP-1 in airway inflammation

Mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a protein with anti-inflammatory properties and the archetypal member of the dual-specificity phosphatases (DUSPs) family that have emerged over the past decade as playing an instrumental role in the regulation of airway inflammation. Not only does MKP-1 serve a critical role as a negative feedback effector, controlling the extent and duration of pro-inflammatory MAPK signalling in airway cells, upregulation of this endogenous phosphatase has also emerged as being one of the key cellular mechanism responsible for the beneficial actions of clinically-used respiratory medicines, including beta(2)-agonists, phosphodiesterase inhibitors and corticosteroids. Herein, we review the role and regulation of MKP-1 in the context of airway inflammation. We initially outline the structure and biochemistry of MKP-1 and summarise the multi-layered molecular mechanisms responsible for MKP-1 production more generally. We then focus in on some of the key in vitro studies in cell types relevant to airway disease that explain how MKP-1 can be regulated in airway inflammation at the transcriptional, post-translation and post-translational level. And finally, we address some of the potential challenges with MKP-1 upregulation that need to be explored further to fully exploit the potential of MKP-1 to repress airway inflammation in chronic respiratory disease

Impact of Systemic Inflammation and Autoimmune Diseases on apoA-I and HDL Plasma Levels and Functions

The cholesterol of high-density lipoproteins (HDLs) and its major proteic component, apoA-I, have been widely investigated as potential predictors of acute cardiovascular (CV) events. In particular, HDL cholesterol levels were shown to be inversely and independently associated with the risk of acute CV diseases in different patient populations, including autoimmune and chronic inflammatory disorders. Some relevant and direct anti-inflammatory activities of HDL have been also recently identified targeting both immune and vascular cell subsets. These studies recently highlighted the improvement of HDL function (instead of circulating levels) as a promising treatment strategy to reduce inflammation and associated CV risk in several diseases, such as systemic lupus erythematosus and rheumatoid arthritis. In these diseases, anti-inflammatory treatments targeting HDL function might improve both disease activity and CV risk. In this narrative review, we will focus on the pathophysiological relevance of HDL and apoA-I levels/functions in different acute and chronic inflammatory pathophysiological conditions

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Clinical and economic outcomes of a &quot;high-touch&quot; clinical management program for intravenous immunoglobulin therapy

Julia Zhu,1 Heather S Kirkham,1 Gretchen Ayer,2 Chi-Chang Chen,3 Rolin L Wade,3 Swapna U Karkare,4 Chester H Robson,1 Jordan S Orange5 1Walgreens, Deerfield, 2Option Care, Bannockburn, IL, 3Quintiles IMS, Plymouth Meeting, PA, 4Quintiles IMS, Deerfield, IL, 5Baylor College of Medicine, Texas Children&rsquo;s Hospital, Houston, TX, USA Objective: To compare clinical and economic outcomes of patients who received intravenous immunoglobulin (IVIG) therapies and were managed by a clinical management program vs the outcomes of matched controls using administrative claim data.Methods: This retrospective cohort study used the PharMetrics Plus&trade; claim database between September 1, 2011 and June 30, 2014. Patients in the intervention group were from a &ldquo;high-touch&rdquo; IVIG clinical management program administered by a home infusion specialty pharmacy. A greedy propensity score matching algorithm was used to identify a control group from non-program patients. Generalized estimating equation models were employed to evaluate differences between cohorts who were followed for 1 year. Results: Clinical outcomes were measured as infections and infusion-related adverse events. The proportion of patients who had serious bacterial infections was significantly lower (4.13% vs 7.75%, P=0.049) in the intervention group (n=242) compared to the control group (n=968). Other clinical outcomes assessed were not different between cohorts (P&gt;0.050). The economic outcomes were measured as healthcare costs. The annual adjusted mean total health care costs of patients in the program were $26,522 lower compared to matched controls, representing a 20$109,476 vs $135,998, P=0.002). A major contribution to this difference ($17,269) was IVIG-related total outpatient cost (intervention vs control groups: $64,080 vs$81,349, P=0.001).Conclusion: The patients in this high-touch IVIG clinical management program appeared to have comparable infections or adverse event rates and significantly lower total health costs compared to their matched controls. Keywords: immunoglobulin, intravenous, management program, clinical outcomes, economic outcome

Characterizing indeterminate (Likert-scored 3/5) peripheral zone prostate lesions with PSA density, PI-RADS scoring and qualitative descriptors on multi-parametric MRI

OBJECTIVE: To determine whether indeterminate (Likert-score 3/5) peripheral zone (PZ) multi-parametric MRI (mpMRI) studies are classifiable by Prostate-Specific Antigen (PSA), PSA density (PSAD), PI-RADS_v2 rescoring and morphological MRI features. METHODS: Men with maximum Likert-score 3/5 within their PZ were retrospectively selected from 330 men who prospectively underwent prostate mpMRI (3T) without an endorectal coil, followed by twenty-zone trans-perineal template prostate mapping biopsies ± focal lesion-targeted biopsy. PSAD was calculated using pre-biopsy PSA and MRI-derived volume. Two readers A and B independently assessed included men with both subjective Likert-score and PI-RADS_v2. Both readers then classified mpMRI morphological features in consensus. Men were divided into two groups: significant cancer (≥Gleason 3+4) or insignificant cancer (≤Gleason 3+3)/no cancer. Comparisons between groups were made separately for PSA&PSAD using Mann-Whitney test and morphological descriptors with Fisher's exact test. PI-RADS_v2 and subjective Likert assessment were descriptively compared and percentage inter-reader agreement calculated. RESULTS: 76 men were eligible for PSA&PSAD analyses, 71 for PI-RADS scoring, and 67 for morphological assessment (excluding significant image artefacts). Unlike PSA (p=0.915), PSAD was statistically different (p=0.004) between the significant 0.19 ng/ml2 (IQR: 0.13-0.29) and non-significant/no cancer 0.13 ng/ml2 (IQR: 0.10-0.17) groups. Presence of mpMRI morphological features wasn't significantly different between groups. Subjective Likert assessment discriminated patients with significant cancer better than PI-RADS_v2. Inter-reader percentage agreement was 83% for subjective Likert-scoring and 56% for PI-RADS_v2. CONCLUSION: PSAD may categorize presence of significant cancer in patients with Likert-scored 3/5 PZ mpMRI findings. Advances in knowledge: PSAD may be used in indeterminate PZ mpMRI to guide decisions between biopsy versus monitoring