Senescence in hepatic stellate cells as a mechanism of liver fibrosis reversal: a putative synergy between retinoic acid and PPAR-gamma signalings

Hepatic stellate cells (HSCs), also known as perisinusoidal cells, are pericytes found in the perisinusoidal space of the liver. HSCs are the major cell type involved in liver fibrosis, which is the formation of scar tissue in response to liver damage. When the liver is damaged, stellate cells can shift into an activated state, characterized by proliferation, contractility and chemotaxis. The activated HSCs secrete collagen scar tissue, which can lead to cirrhosis. Recent studies have shown that in vivo activation of HSCs by fibrogenic agents can eventually lead to senescence of these cells, which would contribute to reversal of fibrosis although it may also favor the insurgence of liver cancer. HSCs in their non-active form store huge amounts of retinoic acid derivatives in lipid droplets, which are progressively depleted upon cell activation in injured liver. Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A, generally required for growth and development. The precise function of retinoic acid and its alterations in HSCs has yet to be elucidated, and nonetheless in various cell types retinoic acid and its receptors (RAR and RXR) are known to act synergistically with peroxisome proliferator-activated receptor gamma (PPAR-gamma) signaling through the activity of transcriptional heterodimers. Here, we review the recent advancements in the understanding of how retinoic acid signaling modulates the fibrogenic potential of HSCs and proposes a synergistic combined action with PPAR-gamma in the reversal of liver fibrosis

Accuracy of MRI skeletal age estimation for subjects 12–19. Potential use for subjects of unknown age

In forensic practice, there is a growing need for accurate methods of age estimation, especially in the cases of young individuals of unknown age. Age can be estimated through somatic features that are universally considered associated with chronological age. Unfortunately, these features do not always coincide with the real chronological age: for these reasons that age determination is often very difficult. Our aim is to evaluate accuracy of skeletal age estimation using Tomei's MRI method in subjects between 12 and 19 years old for forensic purposes. Two investigators analyzed MRI images of the left hand and wrist of 77 male and 74 female caucasian subjects, without chronic diseases or developmental disorders, whose age ranged from 12 to 19 years. Skeletal maturation was determined by two operators, who analyzed all MRI images separately, in blinded fashion to the chronological age. Inter-rater agreement was measured with Pearson (R (2)) coefficient. One of the examiners repeated the evaluation after 6 months, and intraobserver variation was analyzed. Bland-Altman plots were used to determine mean differences between skeletal and chronological age. Inter-rater agreement Pearson coefficient showed a good linear correlation, respectively, 0.98 and 0.97 in males and females. Bland-Altman analysis demonstrated that the differences between chronological and skeletal age are not significant. Spearman's correlation coefficient showed good correlation between skeletal and chronological age both in females (R (2) = 0.96) and in males (R (2) = 0.94). Our results show that MRI skeletal age is a reproducible method and has good correlation with chronological age

Analysis of gut microbiota in rheumatoid arthritis patients. Disease-related dysbiosis and modifications induced by etanercept

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota

Second-line chemotherapy in advanced pancreatic cancer patients before nab-paclitaxel introduction. Retrospective study in Reggio Emilia Clinical Cancer Centre

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Professionalism and the Millbank Tendency: The Political Sociology of New Labour's employees

This article analyses party employees, one of the most under-researched subjects in the study of British political parties. We draw on a blend of quantitative and qualitative data in order to shed light on the social and political profiles of Labour Party staff, and on the question of their professionalisation. The latter theme is developed through a model derived from the sociology of professions. While a relatively limited proportion of party employees conform to the pure ideal-type of professionalism, a considerably greater number manifest enough of the core characteristics of specialisation, commitment, mobility, autonomy and self-regulation to be reasonably described as 'professionals in pursuit of political outcomes'

Low cancer yield in PI-RADS 3 upgraded to 4 by dynamic contrast-enhanced MRI: is it time to reconsider scoring categorization?

Objectives: To evaluate MRI diagnostic performance in detecting clinically significant prostate cancer (csPCa) in peripheral-zone PI-RADS 4 lesions, comparing those with clearly restricted diffusion (DWI-score 4), and those with equivocal diffusion pattern (DWI-score 3) and positive dynamic contrast-enhanced (DCE) MRI. Methods: This observational prospective study enrolled 389 men referred to MRI and, if positive (PI-RADS 3 with PSA-density [PSAD] ≥ 0.15 ng/mL/mL, 4 and 5), to MRI-directed biopsy. Lesions with DWI-score 3 and positive DCE were classified as “PI-RADS 3up,” instead of PI-RADS 4. Univariable and multivariable analyses were implemented to determine features correlated to csPCa detection. Results: Prevalence of csPCa was 14.5% and 53.3% in PI-RADS categories 3up and 4, respectively (p < 0.001). MRI showed a sensitivity of 100.0%, specificity 40.9%, PPV 46.5%, NPV 100.0%, and accuracy 60.9% for csPCa detection. Modifying the threshold to consider MRI positive and to indicate biopsy (same as previously described, but PI-RADS 3up only when associated with elevated PSAD), the sensitivity changed to 93.9%, specificity 57.2%, PPV 53.0%, NPV 94.8%, and accuracy 69.7%. Age (p < 0.001), PSAD (p < 0.001), positive DWI (p < 0.001), and PI-RADS score (p = 0.04) resulted in independent predictors of csPCa. Conclusions: Most cases of PI-RADS 3up were false-positives, suggesting that upgrading peripheral lesions with DWI-score 3 to PI-RADS 4 because of positive DCE has a detrimental effect on MRI accuracy, decreasing the true prevalence of csPCa in the PI-RADS 4 category. PI-RADS 3up should not be upgraded and directed to biopsy only if associated with increased PSAD. Key Points: • As per PI-RADS v2.1 recommendations, in case of a peripheral zone lesion with equivocal diffusion-weighted imaging (DWI score 3), but positive dynamic contrast-enhanced (DCE) MRI, the overall PI-RADS score should be upgraded to 4. • The current PI-RADS recommendation of upgrading PI-RADS 3 lesions of the peripheral zone to PI-RADS 4 because of positive DCE decreased clinically significant prostate cancer detection rate in our series. • According to our results, the most accurate threshold for setting indication to prostate biopsy is PI-RADS 3 or PI-RADS 3 with positive DCE both associated with increased PSA density

Electrochemotherapy for solid tumors: literature review and presentation of a novel endoscopic approach

Background: Electrochemotherapy (ECT) is a minimally invasive and safe treatment gaining positive and long-lasting antitumoral results that are receiving the attention of the scientific community. It is a local treatment that combines the use of electroporation and the administration of cytotoxic drugs to induce cell death in the target tissue. ECT is largely used for the treatment of cutaneous and subcutaneous lesions, and good results have been reported for the treatment of deep visceral tumors. The latest literature review is provided. Moreover, in line with its development for the treatment of visceral tumors in this article, we describe a novel approach of ECT: endoscopic treatment of colorectal cancer. Endoscopic ECT application was combined with systemic chemotherapy in the treatment of obstructing rectal cancer without prospective surgery. A good response after ECT was described: concentric involvement of the rectum was reduced, and no stenosing lesions were detected. Conclusions: Clinical studies have demonstrated that ECT is a very effective treatment for tumors of different histologic types and localizations. Endoscopic treatment for gastrointestinal cancer is an innovative application of ECT. The combination of systemic treatment and ECT was safe and highly effective in the treatment of colorectal cancer, especially when obstructive, giving the patient a significant gain in quality of life

An update of pitfalls in prostate mpMRI: a practical approach through the lens of PI-RADS v. 2 guidelines

ObJECTIVES: The aim of the current report is to provide an update in the imaging interpretation of prostate cancer on multiparametric magnetic resonance imaging (mpMRI), with a special focus on how to discriminate pathological tissue from the most common pitfalls that may be encountered during daily clinical practice using the Prostate Imaging Reporting and Data System (PI-RADS) version 2 guidelines. METHODS: All the cases that are shown in this pictorial review comply with the European Society of Urogenital Radiology (ESUR) guidelines for technical mpMRI requirements. RESULTS: Despite the standardised manner to report mpMRI (PI-RADS v. 2), some para-physiologic appearances of the prostate can mimic cancer. As such, it is crucial to be aware of these pitfalls, in order to avoid the under/overestimation of prostate cancer. CONCLUSIONS: A detailed knowledge of normal and abnormal findings in mpMRI of the prostate is pivotal for an accurate management of the wide spectrum of clinical scenarios that radiologists may encounter during their daily practice. TEACHING POINTS: • Some para-physiologic appearances of the prostate may mimic cancer. • Knowledge of normal and abnormal findings in prostate mpMRI is pivotal. • Any radiologist involved in prostate mpMRI reporting should be aware of pitfalls

Interobserver reproducibility of the PRECISE scoring system for prostate MRI on active surveillance: results from a two-centre pilot study

OBJECTIVES: We aimed to determine the interobserver reproducibility of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) criteria for magnetic resonance imaging in patients on active surveillance (AS) for prostate cancer (PCa) at two different academic centres. METHODS: The PRECISE criteria score the likelihood of clinically significant change over time. The system is a 1-to-5 scale, where 1 or 2 implies regression of a previously visible lesion, 3 denotes stability and 4 or 5 indicates radiological progression. A retrospective analysis of 80 patients (40 from each centre) on AS with a biopsy-confirmed low- or intermediate-risk PCa (i.e. ≤ Gleason 3 + 4 and prostate-specific antigen ≤ 20 ng/ml) and ≥ 2 prostate MR scans was performed. Two blinded radiologists reported all scans independently and scored the likelihood of radiological change (PRECISE score) from the second scan onwards. Cohen's κ coefficients and percent agreement were computed. RESULTS: Agreement was substantial both at a per-patient and a per-scan level (κ = 0.71 and 0.61; percent agreement = 79% and 81%, respectively) for each PRECISE score. The agreement was superior (κ = 0.83 and 0.67; percent agreement = 90% and 91%, respectively) when the PRECISE scores were grouped according to the absence/presence of radiological progression (PRECISE 1-3 vs 4-5). Higher inter-reader agreement was observed for the scans performed at University College London (UCL) (κ = 0.81 vs 0.55 on a per-patient level and κ = 0.70 vs 0.48 on a per-scan level, respectively). The discrepancies between institutions were less evident for percent agreement (80% vs 78% and 86% vs 75%, respectively). CONCLUSIONS: Expert radiologists achieved substantial reproducibility for the PRECISE scoring system, especially when data were pooled together according to the absence/presence of radiological progression (PRECISE 1-3 vs 4-5). KEY POINTS: • Inter-reader agreement between two experienced prostate radiologists using the PRECISE criteria was substantial. • The agreement was higher when the PRECISE scores were grouped according to the absence/presence of radiological progression (i.e. PRECISE 1-3 vs PRECISE 4 and 5). • Higher inter-reader agreement was observed for the scans performed at UCL, but the discrepancies between institutions were less evident for percent agreement