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    Electronic patient reported outcomes to support care of patients with traumatic brain injury: PRiORiTy study qualitative protocol.

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    INTRODUCTION Traumatic brain injury (TBI) represents a major health and socioeconomic problem internationally. The expansive nature of injuries results in a heterogeneous population. The degree and type of long-term impacts following TBI and improvement following injury are highly variable. The use of electronic Patient Reported Outcomes Measures (ePROMs) could help identify residual impacts of TBI and support patient management and care. The Patient Reported Outcomes Research in Trauma study is a qualitative study exploring the long-term symptoms and impacts that are experienced by those with TBI and the potential utility of an ePROM platform to collect real-time information on patient symptoms and quality of life to inform treatment and identify support needs. METHODS AND ANALYSIS Semi-structured telephone and face-to-face interviews will be conducted with approximately 30-40 individuals recruited from five groups: (1) people with TBI; (2) carers and relatives of individuals with TBI; (3) TBI healthcare professionals; (4) researchers and (5) third sector staff members and volunteers working with those with TBI. Data will be analysed using directed thematic analysis employing an iterative coding frame that will be modified as analysis progresses. Intercoder triangulation will be employed to enhance credibility. ETHICS AND DISSEMINATION This study was approved by the West Midlands-Black Country Research Ethics Committee (Ref: 18/WM/0033). Findings will be disseminated via conference presentations, peer-reviewed journals, social media (@CPROR_UoB; http://www.birmingham.ac.uk/cpror) and the National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre

    Progression of mycosis fungoides occurs through divergence of tumor immunophenotype by differential expression of HLA-DR.

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    Immunotherapy is a valuable treatment for many cancer patients, and there is considerable interest in understanding the mechanisms of immune evasion to guide appropriate management. Mycosis fungoides (MF) is a malignant disorder of skin-homing CD4 T cells, and it exhibits a highly variable clinical course during which the tumor-specific immune response may be an important determinant. An unusual feature of MF is that tumor-infiltrating lymphocytes (TILs) must attempt to control a malignant cell from within their own lineage. We obtained skin biopsies and blood from 43 patients with CD4 MF and undertook a detailed phenotypic and functional analysis of CD4 and CD8 T cells. Clonotypic TCRBV staining allowed delineation of malignant and reactive CD4 subsets. CD4 and CD8 TILs displayed a comparable "exhausted" phenotype that was characterized by expression of PD-1 and TIGIT but retained cytotoxic activity and production of interferon-γ and interleukin-17 in early-stage disease. In contrast, tumor cells were much more heterogeneous and were divided into 3 discrete subsets based on differential expression of HLA-DR: "cold" (DR), "exhausted" (DR PD-1), and "evasive" (DR PD-L1) phenotypes. Disease progression was associated with increasing divergence of the tumor phenotype away from that of TILs and reduced functional activity within TILs. These observations reveal that the phenotype and function of TIL populations are constrained at all stages of disease, whereas the tumor evolves discrete phenotypic profiles of escape during clinical progression. The findings should help to direct appropriate immunotherapeutic interventions for individual patients

    Reliability of patellotrochlear index in patellar height assessment on MRI-correction for variation due to change in knee flexion.

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    OBJECTIVES To assess the reliability of patellotrochlear Index (PTI) in patellar height assessment on successive MRI scans in asymptomatic patients. MATERIALS AND METHODS Sixty-four patients with two successive MRI scans (128 studies) of the same knee for non-patellofemoral joint symptoms were identified retrospectively. PTI and knee flexion angle were assessed independently by three observers to assess interobserver reliability. The effect of knee flexion on PTI was assessed by comparing the change in values of PTI in each patient correlated with change in knee flexion. RESULTS Sixty-four MRIs of patients (M:F) aged between 18 and 35 years (mean 24.6) years were assessed. The mean PTI for initial scan group was 0.33% (95% CI: 0.29-0.37; SD: 0.15) and consecutive scan group was 0.30% (CI: 0.27-0.33; SD: 0.3). The difference was not significant (p = 0.097 using a paired t test) with high inter-observer correlation (0.9) in both sets. Spearman's rho for knee flexion angle and PTI was found to be positive and statistically significant (0.41; p = 0.001). A linear regression model was derived using a scatter chart of change in PTI with change in knee flexion for each patient. The gradient of the linear regression line was used to estimate a cPTI (corrected PTI) value (corrected to 0 degrees of knee flexion), defined as cPTI = PTI - 1.3a (a = knee flexion angle). CONCLUSIONS This study demonstrates high inter-observer correlation of PTI on MRI and high test-retest reliability indicating unconscious quadriceps contraction does not change the index sufficiently. Knee flexion significantly alters PTI, increased patellotrochlear engagement with flexion increases the index. We propose use of the formula cPTI = PTI -1.3a to correct the index to 0 degree knee flexion in clinical practice

    Fully automated real-time PCR for EGFR testing in non-small cell lung carcinoma.

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    Molecular testing for mutations in the EGFR gene is commonplace for patients with non-small cell lung cancer (NSCLC). These patients are often very sick and management decisions need to be made urgently. In many cases, the results of molecular testing are needed the same day, in order to start targeted therapy and allow maximum benefit for patients. The Idylla™ EGFR Mutation Test offers rapid results within three hours of requesting. This study aimed to assess the concordance of Idylla™ EGFR Mutation Test results with current standard tests. Forty formalin-fixed, paraffin-embedded NSCLC tumour cases (20 EGFR mutant and EGFR 20 wild type) were analysed by the Idylla™ EGFR Mutation Test (CE-IVD) and compared with PCR and NGS methodologies. The overall concordance between Idylla™ and standard testing was 92.5% (95% CI 80.14% to 97.42%) and the specificity of Idylla™ was 100% (95% CI 83.89% to 100%). The sensitivity was affected by loss of tumour content in tissue blocks in a small number of NGS cases; however, comparing Idylla™ with PCR alone, there was 100% concordance (95% CI 89.85% to 100%). The Idylla™ EGFR Mutation Test shows comparative accuracy to routine PCR testing for the most common EGFR mutations in NSCLC. The Idylla™ also offers significantly reduced turn-around times compared with existing modalities and therefore the platform would be a useful addition to many molecular diagnostics units

    Simple Magnetic Resonance Scores Associate With Outcomes of Patients With Primary Sclerosing Cholangitis.

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    BACKGROUND & AIMS Primary sclerosing cholangitis (PSC) has a variable, often progressive course. Magnetic resonance cholangiography (MRC) is used in diagnosis of PSC. Magnetic resonance risk scoring systems, called Anali without and with gadolinium, are used to predict disease progression, determined by radiologic factors. We aimed to assess the prognostic value of Anali scores in patients with PSC and validate our findings in a separate cohort. METHODS We performed a retrospective study of patients with large-duct PSC (internal cohort, 119 patients in France and external cohort, 119 patients in Canada, Italy, and United Kingdom). All the first-available MRC results were reviewed by 2 radiologists and the Anali scores were calculated: Anali without gadolinium= (1x dilatation of intrahepatic bile ducts) + (2x dysmorphy) + (1x portal hypertension); Anali with gadolinium= (1x dysmorphy) + (1x parenchymal enhancement heterogeneity). The primary endpoint was survival without liver transplantation or cirrhosis decompensation. The prognostic value of Anali scores was assessed by Cox regression modeling. RESULTS During a total of 549 patient-years for the internal cohort and 497 patient-years for the external cohort, we recorded 2 and 8 liver transplantations, 4 and 3 liver-related deaths, 26 and 25 cirrhosis decompensations, respectively. In the univariate analysis, factors associated with survival without liver transplantation or cirrhosis decompensation in the internal cohort were: serum levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and albumin and Anali scores. Anali scores without and with gadolinium identified patients survival without liver transplantation or cirrhosis decompensation with a c-statistic of 0.89 (95% CI, 0.84-0.95) and 0.75 (95% CI, 0.64-0.87), respectively. Independent prognostic factors identified by multivariate analysis were Anali scores and bilirubinemia. The prognostic value of Anali scores was confirmed in the external cohort. CONCLUSIONS In internal and external cohorts, we found that Anali scores, determined from MRC, associate with outcomes of patients with PSCs. These scores might be used as prognostic factors

    Properties and use of a honey dressing and gel in wound management.

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    Wound management is a major clinical challenge and puts a significant financial burden on the NHS. Because of the rise in long-term conditions including diabetes, obesity and an ageing population, practitioners regularly encounter a wide variety of wound types. In recent years, there has been a resurgence of interest in the use of medical-grade honey in the management of wounds. Honey is anti-inflammatory in action and has the capability to treat local infection, promote autolytic debridement, deodorise wounds and promote granulation tissue. Revamil is a recent addition to the range of honey dressings available and is intended to manage the majority of problems that may arise during wound care episodes. The attributes of Revamil will be illustrated through four case studies

    Aortic Conduit Aneurysm and Enteric Fistula Formation in a Post Liver Transplant Patient: A potential causative role for CMV?

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    Hepatic arterial aortic conduits can be used as an alternative means of revascularising the donor liver when the native recipient hepatic artery (HA) cannot be used. Cytomegalovirus (CMV) is a common Herpesviridae infection in patients who have undergone solid organ transplants. It can be asymptomatic but may cause fever and invasive disease affecting any organ system. Here we describe the first case in the literature of an aortic conduit aneurysm and concurrent CMV viremia following liver transplantation. We speculate on a causative role for CMV in the development of the aneurysm. This article is protected by copyright. All rights reserved

    Dried blood spot and mini-tube blood sample collection kits for postal HIV testing services: a comparative review of successes in a real-world setting.

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    OBJECTIVES This is a comparative review between using dried blood spot (DBS) and mini-tube (MT) HIV sampling kits as part of an online sexually transmitted infection (STI) postal testing service. England has recently seen increases in internet-based and postal (eHealth) STI services. Expanding accessibility and testing for patients, cost implications and narrowing the HIV undiagnosed margin are drivers for this. METHODS In 2017, data were reviewed from an online postal STI kit requesting service at a time of transitioning from MT to DBS. We compared the STI postal kit and HIV blood sample return rates, and the successful processing/analysis rates of the DBS and MT kits. Descriptive statistics were applied to participant characteristics, with Pearson's χ or Fisher exact test used to demonstrate statistical differences. We also describe and calculate a 'request-to-result ratio' (RRR) for both kit types. The RRR is defined as the number of online kit requests required to produce one successfully analysed result. RESULTS 550 STI postal kit requests from a North-West of England region were reviewed from 13 June 2017 to 22 September 2017 (275 MT, 275 DBS). Baseline characteristics between the two groups were comparable (63% woman, 90% white British and 86% heterosexual with a median age of 26 years). The successful processing rate for the DBS was 98.8% c.f. 55.7% for the MT (p<0.001). The RRR for MT was 2.96, c.f. 1.70 for DBS. There was a 5.4% false positive HIV rate in the MT c.f. none in the DBS. CONCLUSIONS This comparative analysis suggests that in this community setting, the use of postal HIV DBS kits resulted in a significantly improved RRR compared with MT. The biggest factor was the large number of MT samples not analysed due to inadequate blood volumes. The unexpected level of false positive results in the MT samples needs confirming in larger studies

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