Blood Epstein-Barr virus DNA does not predict outcome in advanced HIV-associated Hodgkin lymphoma

In HIV-seronegative patients with advanced Hodgkin lymphoma (HL), Epstein-Barr virus (EBV) viraemia at diagnosis predicts a worse progression-free survival (PFS), independent of the International Prognostic Score. However, its role in HIV-associated HL is uncharacterised. We collected clinico-pathologic and treatment data from a prospective series of 44 HIV-associated HLs from 2000 to 2016. We evaluated circulating EBV DNA as a prognostic factor on uni- and multivariable analyses in relationship to the International Prognostic Index criteria. In 44 patients with HIV-associated HL, EBV was detected by in situ hybridisation in all diagnostic biopsies. Blood EBV DNA was detectable in 26 patients (59%) with a median of 600 copies/mL (range 0-161,000). EBV DNA was independent of CD4 cell count (p = 0.9) or HIV viral load (p = 0.6) and did not predict PFS (HR 1.6, 95% CI 0.39-6.7, p = 0.49). EBV DNA is not a prognostic trait in HIV-associated HL. Prognostication in HIV-associated HL should be solely based on the International Prognostic Index criteria

Investigating the process of ethical approval in citizen science research. The case of public health

Undertaking citizen science research in Public Health involving human subjects poses significant challenges concerning the traditional process of ethical approval. It requires an extension of the ethics of protection of research subjects in order to include the empowerment of citizens as citizen scientists. This paper investigates these challenges and illustrates the ethical framework and the strategies developed within the CitieS-Health project. It also proposes first recommendations generated from the experiences of five citizen science pilot studies in environmental epidemiology within this project

Feasibility of diffusion tensor imaging (DTI) with fibre tractography of the normal female pelvic floor

To prospectively determine the feasibility of diffusion tensor imaging (DTI) with fibre tractography as a tool for the three-dimensional (3D) visualisation of normal pelvic floor anatomy. Five young female nulliparous subjects (mean age 28 ± 3 years) underwent DTI at 3.0T. Two-dimensional diffusion-weighted axial spin-echo echo-planar (SP-EPI) pulse sequence of the pelvic floor was performed, with additional T2-TSE multiplanar sequences for anatomical reference. Fibre tractography for visualisation of predefined pelvic floor and pelvic wall muscles was performed offline by two observers, applying a consensus method. Three eigenvalues (λ1, λ2, λ3), fractional anisotropy (FA) and mean diffusivity (MD) were calculated from the fibre trajectories. In all subjects fibre tractography resulted in a satisfactory anatomical representation of the pubovisceral muscle, perineal body, anal - and urethral sphincter complex and internal obturator muscle. Mean FA values ranged from 0.23 ± 0.02 to 0.30 ± 0.04, MD values from 1.30 ± 0.08 to 1.73 ± 0.12 × 10(-)³ mm²/s. Muscular structures in the superficial layer of the pelvic floor could not be satisfactorily identified. This study demonstrates the feasibility of visualising the complex three-dimensional pelvic floor architecture using 3T-DTI with fibre tractography. DTI of the deep female pelvic floor may provide new insights into pelvic floor disorder

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates

Pancreatic cancer foiled by a switch of tumour subtype

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers in Western society1 because it tends to be diagnosed late and responds poorly to therapy. PDAC tumours fall into two main groups2–4: a ‘classical’ subtype, and a more aggressive ‘squamous’ subtype in which pancreatic cells fail to undergo proper differentiation. The squamous subtype often involves mutations in members of the COMPASS-like complex — a group of methyltransferase and demethylase enzymes that, respectively, add or remove methyl groups from lysine amino-acid residues on histone proteins, around which DNA is packaged. Such histone modification can lead to changes in the expression of histone-associated genes involved in pancreatic-cell differentiation. Writing in Cancer Cell, Andricovich et al.5 demonstrate the role of mutations in one member of this complex, KDM6A, in driving the squamous PDAC subtype

Clinical results with microwave thermotherapy of benign prostatic hyperplasia

Since October 1990, 414 patients with micturition complaints due to benign prostatic hyperplasia were treated with transurethral microwave thermotherapy (TUMT). In this study 130 patients are presented who were treated according to a strict protocol. The technique of treatment as well as the inclusion and exclusion criteria for TUMT treatment are discussed. With a follow-up period of 1 year after TUMT, a clear subjective improvement was seen in 63% of the patients. Objective improvement, however, is less pronounced. The main complication of TUMT is a urinary retention, which can be treated with a transurethral catheter. This catheter can be removed in most patients after 1 wee