Identification of HPV genotypes causing cervical precancer using tissue-based genotyping

Identification of high-risk human papillomavirus genotypes causing cervical precancer is crucial for informing HPV vaccine development and efficacy studies, and for determining which types to include in next-generation genotyping assays. Co-occurrence of hrHPV infections is common and complicates carcinogenicity assessment; accurate attribution requires tissue-based genotyping of precancers. We included all women with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) from the Biopsy Study, an observational study of 690 women enrolled between 2009 and 2012 at the University of Oklahoma. Tissue-based genotyping, including whole tissue sections (WTS) and laser-capture microdissection (LCM), was performed on all precancers with multiple hrHPV infections detected in cytology, totaling over 1,800 HPV genotyping assays. Genotype attribution was compared to hierarchical and proportional hrHPV-type attribution models. Of 276 women with CIN2+, 122 (44.2%) had multiple hrHPV genotypes in cytology. Of 114 women with genotyping data, 94 had one or more hrHPV detected in tissue. Seventy-one women (75.5%) had a single causal hrHPV genotype, while 23 women had multiple hrHPV genotypes causing CIN2+. Ten women had multiple causal infections in a single biopsy, contrary to the previous notion that each lesion is caused by a single type only. While HPV16 was the predominant causal hrHPV genotype using all approaches, the hierarchical model overattributed HPV16, whereas other causal hrHPV genotypes, particularly HPV18 and HPV35, were underattributed. Understanding true causal genotypes is important for the evaluation of vaccine efficacy, to estimate the extent of unmasking, and for type-specific risk assessment in screening and management.     

Hierarchical non‐negative matrix factorization to characterize brain tumor heterogeneity using multi‐parametric MRI

Tissue characterization in brain tumors and, in particular, in high‐grade gliomas is challenging as a result of the co‐existence of several intra‐tumoral tissue types within the same region and the high spatial heterogeneity. This study presents a method for the detection of the relevant tumor substructures (i.e. viable tumor, necrosis and edema), which could be of added value for the diagnosis, treatment planning and follow‐up of individual patients. Twenty‐four patients with glioma [10 low‐grade gliomas (LGGs), 14 high‐grade gliomas (HGGs)] underwent a multi‐parametric MRI (MP‐MRI) scheme, including conventional MRI (cMRI), perfusion‐weighted imaging (PWI), diffusion kurtosis imaging (DKI) and short‐TE ¹H MRSI. MP‐MRI parameters were derived: T₂, T₁ + contrast, fluid‐attenuated inversion recovery (FLAIR), relative cerebral blood volume (rCBV), mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and the principal metabolites lipids (Lip), lactate (Lac), N‐acetyl‐aspartate (NAA), total choline (Cho), etc. Hierarchical non‐negative matrix factorization (hNMF) was applied to the MP‐MRI parameters, providing tissue characterization on a patient‐by‐patient and voxel‐by‐voxel basis. Tissue‐specific patterns were obtained and the spatial distribution of each tissue type was visualized by means of abundance maps. Dice scores were calculated by comparing tissue segmentation derived from hNMF with the manual segmentation by a radiologist. Correlation coefficients were calculated between each pathologic tissue source and the average feature vector within the corresponding tissue region. For the patients with HGG, mean Dice scores of 78%, 85% and 83% were obtained for viable tumor, the tumor core and the complete tumor region. The mean correlation coefficients were 0.91 for tumor, 0.97 for necrosis and 0.96 for edema. For the patients with LGG, a mean Dice score of 85% and mean correlation coefficient of 0.95 were found for the tumor region. hNMF was also applied to reduced MRI datasets, showing the added value of individual MRI modalities. Copyright © 2015 John Wiley & Sons, Ltd.     

Factors associated with relapses among patients treated for acute urticaria

The benefit of corticosteroids in acute urticaria is controversial. Our objective was to determine the factors associated with relapses in patients presenting with acute urticaria. A retrospective observational study, including all patients with acute urticaria who visited the angioedema reference center of Academic Public Hospitals – Saint‐Antoine in Paris between January 2015 and June 2017, was conducted. The study inclusion criterion was a diagnosis of acute urticaria in an adult patient. The urticaria was spontaneous or inducible urticaria. The primary outcome was relapse at day 7 and the secondary outcome was relapse at week 6. A total of 184 patients with a first episode of acute urticaria were included. Most of the patients were female (66%) with a mean age of 42 ± 16 years. Corticosteroid administration for treatment of acute urticaria was used in 102 (55%) patients. Overall, 85 (46%) patients had relapses after less than 7 days whereas 168 (91%) patients had relapses after more than 6 weeks. In univariate analysis, the rate of corticosteroid administration was significantly higher in cases of relapse after less than 7 days. No difference in relapse rates after more than 6 weeks appeared. In the multivariate analysis, the independent factor associated with relapses after less than 7 days was the administration of corticosteroids as treatment of acute urticaria (odds ratio, 1.93; 95% confidence interval, 1.06–3.57; P = 0.03). The prevalence of corticosteroid administration for patients with acute urticaria was high. Corticosteroid administration was an independent risk factor associated with relapses after less than 7 days.     

Cutaneous nociception: Role of keratinocytes

Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous nociception. While intra‐epidermal nerve endings were classically considered as the exclusive transducers of cutaneous noxious stimuli, it has now been demonstrated that epidermal keratinocytes can initiate nociceptive responses, like Merkel cells do for the innocuous mechanotransduction. In the light of recent in vivo findings, this article outlines this paradigm shift that points to a not yet considered population of sensory epidermal cells.     

Skin closure with 2-octyl cyanoacrylate and polyester mesh after primary total knee arthroplasty offers superior cosmetic outcomes and patient satisfaction compared to staples: a prospective trial

European Journal of Orthopaedic Surgery & Traumatology - The goals of this study were to compare patient satisfaction and wound-related complications in patients receiving 2-octyl cyanoacrylate...