Texture analysis on preoperative contrast-enhanced magnetic resonance imaging identifies microvascular invasion in hepatocellular carcinoma

Background: Radiomic texture analysis quantifies tumor heterogeneity. The aim of this study is to determine if radiomics can predict biologic aggressiveness in HCC and identify tumors with MVI.Methods: Single-center, retrospective review of HCC patients undergoing resection/ablation with curative intent from 2009 to 2017. DICOM images from preoperative MRIs were analyzed with texture analysis software. Texture analysis parameters extracted on T1, T2, hepatic arterial phase (HAP) and portal venous phase (PVP) images. Multivariate logistic regression analysis evaluated factors associated with MVI.Results: MVI was present in 52.2% (n = 133) of HCCs. On multivariate analysis only T1 mean (OR = 0.97, 95%CI 0.95-0.99, p = 0.043) and PVP entropy (OR = 4.7, 95%CI 1.37-16.3, p = 0.014) were associated with tumor MVI. Area under ROC curve was 0.83 for this final model. Empirical optimal cutpoint for PVP tumor entropy and T1 tumor mean were 5.73 and 23.41, respectively. At these cutpoint values, sensitivity was 0.68 and 0.5, respectively and specificity was 0.64 and 0.86. When both criteria were met, the probability of MVI in the tumor was 87%.Conclusion: Tumor entropy and mean are both associated with MVI. Texture analysis on preoperative imaging correlates with microscopic features of HCC and can be used to predict patients with high-risk tumors

Removal of babies at birth and the moral distress of midwives

Background Midwives and nurses appear vulnerable to moral distress when caring for women whose babies are removed at birth. They may experience professional dissatisfaction and their relationships with women, families and colleagues may be compromised. The impact of moral distress may manifest as anger, guilt, frustration, anxiety and a desire to give up their profession. While there has been much attention exploring the concept of moral distress in midwifery, this is the first study to explore its association in this context. Aim This article explores midwives’ experiences of moral distress when providing care to women whose babies were removed at birth and gives valuable insight into an issue nurses and midwives encounter in their profession. Methods Four mothers and eight midwives took part in this research. Narrative inquiry incorporating photo-elicitation techniques was used to generate data; mothers were interviewed face to face and midwives through focus groups. The images and audio data were collected, transcribed and analysed for emerging themes. For the purpose of this article, only the midwives’ stories are reported. This research received a favourable ethical opinion from the University of Surrey Ethics committee. Ethical considerations This study received a favourable ethical approval from a higher education institutes ethics committee. Results Midwives who care for women whose babies are removed at birth report it as one of the most distressing areas of contemporary clinical practice. Furthermore, they report feelings of guilt, helplessness and betrayal of the midwife–mother relationship. Many of the midwives in this study state that these experiences stay with them for a long time, far more than more joyful aspects of their role. Conclusion Midwives experience moral distress. Support systems, education and training must be available to them if we are to reduce the long-term impact upon them, alleviate their distress and prevent them from leaving the profession. </jats:sec

Diagnosis and management of Neuro-Behçet's disease: international consensus recommendations.

Neuro-Behçet's disease (NBD) is one of the more serious manifestations of Behçet's disease (BD), which is a relapsing inflammatory multisystem disease with an interesting epidemiology. Though NBD is relatively uncommon, being potentially treatable, neurologists need to consider it in the differential diagnosis of inflammatory, infective, or demyelinating CNS disorders. Evidence-based information on key issues of NBD diagnosis and management is scarce, and planning for such studies is challenging. We therefore initiated this project to develop expert consensus recommendations that might be helpful to neurologists and other clinicians, created through an extensive literature review and wide consultations with an international advisory panel, followed by a Delphi exercise. We agreed on consensus criteria for the diagnosis of NBD with two levels of certainty in addition to recommendations on when to consider NBD in a neurological patient, and on the use of various paraclinical tests. The management recommendations included treatment of the parenchymal NBD and cerebral venous thrombosis, the use of disease modifying therapies, prognostic factors, outcome measures, and headache in BD. Future studies are needed to validate the proposed criteria and provide evidence-based treatments

Cancer treatment-related neuropathic pain:proof of concept study with menthol—a TRPM8 agonist

PURPOSE: Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol. PATIENTS AND METHODS: Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4–6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4–6 weeks. Secondary outcomes included changes in function, mood and skin sensation. RESULTS: Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood (P = 0.0004), catastrophising (P = 0.001), walking ability (P = 0.008) and sensation (P < 0.01) were also observed. CONCLUSION: This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required

Anomalous J/ψJ/\psi suppression in Pb-Pb interactions at 158 GeV per nucleon

The Drell-Yan and J/psi cross-sections measured in Pb-Pb collisions are compared with the values extrapolated from the results obtained in proton and light ion induced reactions. While the Drell-Yan production exhibits the normal expected behaviour, the yield of J/psi in Pb-Pb interactions is abnormally low, as it lies 9 standard deviations below the expected value. Moreover, the departure from the expected behaviour increases significantly from peripheral to central collisions. (C) 1997 Elsevier Science B.V

Efficacy of a family practice-based lifestyle intervention program to increase physical activity and reduce clinical and physiological markers of vascular health in patients with high normal blood pressure and/or high normal blood glucose (SNAC): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Previous interventions to increase physical activity and reduce cardiovascular risk factors have been targeted at individuals with established disease; less attention has been given to intervention among individuals with high risk for disease nor has there been determination of the influence of setting in which the intervention is provided. In particular, family practice represents an ideal setting for the provision and long-term maintenance of lifestyle interventions for patients at risk (ie high-normal blood pressure or impaired glucose tolerance).</p> <p>Methods/design</p> <p>The Staged Nutrition and Activity Counseling (SNAC) study is a randomized clustered design clinical trial that will investigate the effectiveness and efficacy of a multi-component lifestyle intervention on cardiovascular disease risk factors and vascular function in patients at risk in primary care. Patients will be randomized by practice to either a standard of care lifestyle intervention or a behaviourally-based, matched prescriptive physical activity and diet change program. The primary goal is to increase physical activity and improve dietary intake according to Canada's Guides to Physical Activity Healthy Eating over 24 months. The primary intention to treat analysis will compare behavioral, physiological and metabolic outcomes at 6, 12 and 24 months post-randomization including estimation of incident hypertension and/or diabetes.</p> <p>Discussion</p> <p>The design features of our trial, and the practical problems (and solutions) associated with implementing these design features, particularly those that result in potential delay between recruitment, baseline data collection, randomization, intervention, and assessment will be discussed. Results of the SNAC trial will provide scientific rationale for the implementation of this lifestyle intervention in primary care.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN:42921300">ISRCTN:42921300</a></p

Molecular pathway profiling of T lymphocyte signal transduction pathways; Th1 and Th2 genomic fingerprints are defined by TCR and CD28-mediated signaling

Contains fulltext : 108719.pdf (publisher's version ) (Open Access)BACKGROUND: T lymphocytes are orchestrators of adaptive immunity. Naive T cells may differentiate into Th1, Th2, Th17 or iTreg phenotypes, depending on environmental co-stimulatory signals. To identify genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli and pathway inhibitors. Results from these experiments were validated in a human experimental setting using whole blood and purified CD4+ Tcells. RESULTS: Calcium-dependent activation of T cells using CD3/CD28 and PMA/CD3 stimulation induced a Th1 expression profile reflected by increased expression of T-bet, RUNX3, IL-2, and IFNgamma, whereas calcium-independent activation via PMA/CD28 induced a Th2 expression profile which included GATA3, RXRA, CCL1 and Itk. Knock down with siRNA and gene expression profiling in the presence of selective kinase inhibitors showed that proximal kinases Lck and PKCtheta are crucial signaling hubs during T helper cell activation, revealing a clear role for Lck in Th1 development and for PKCtheta in both Th1 and Th2 development. Medial signaling via MAPkinases appeared to be less important in these pathways, since specific inhibitors of these kinases displayed a minor effect on gene expression. Translation towards a primary, whole blood setting and purified human CD4+ T cells revealed that PMA/CD3 stimulation induced a more pronounced Th1 specific, Lck and PKCtheta dependent IFNgamma production, whereas PMA/CD28 induced Th2 specific IL-5 and IL-13 production, independent of Lck activation. PMA/CD3-mediated skewing towards a Th1 phenotype was also reflected in mRNA expression of the master transcription factor Tbet, whereas PMA/CD28-mediated stimulation enhanced GATA3 mRNA expression in primary human CD4+ Tcells. CONCLUSIONS: This study identifies stimulatory pathways and gene expression profiles for in vitro skewing of T helper cell activation. PMA/CD3 stimulation enhances a Th1-like response in an Lck and PKCtheta dependent fashion, whereas PMA/CD28 stimulation results in a Th2-like phenotype independent of the proximal TCR-tyrosine kinase Lck. This approach offers a robust and fast translational in vitro system for skewed T helper cell responses in Jurkat T cells, primary human CD4+ Tcells and in a more complex matrix such as human whole blood