Magnetic resonance tumor regression grade (MR-TRG) to assess pathological complete response following neoadjuvant radiochemotherapy in locally advanced rectal cancer

This study aims to evaluate the feasibility of a magnetic resonance (MR) automatic method for quantitative assessment of the percentage of fibrosis developed within locally advanced rectal cancers (LARC) after neoadjuvant radiochemotherapy (RCT). A total of 65 patients were enrolled in the study and MR studies were performed on 3.0 Tesla scanner; patients were followed-up for 30 months. The percentage of fibrosis was quantified on T2-weighted images, using automatic K-Means clustering algorithm. According to the percentage of fibrosis, an optimal cut-off point for separating patients into favorable and unfavorable pathologic response groups was identified by ROC analysis and tumor regression grade (MR-TRG) classes were determined and compared to histopathologic TRG. An optimal cut-off point of 81% of fibrosis was identified to differentiate between favorable and unfavorable pathologic response groups resulting in a sensitivity of 78.26% and a specificity of 97.62% for the identification of complete responders (CRs). Interobserver agreement was good (0.85). The agreement between P-TRG and MR-TRG was excellent (0.923). Significant differences in terms of overall survival (OS) and disease free survival (DFS) were found between favorable and unfavorable pathologic response groups. The automatic quantification of fibrosis determined by MR is feasible and reproducible

Hepatocellular carcinoma in adult thalassemia patients: an expert opinion based on current evidence

Beta-thalassemia represents a heterogeneous group of haemoglobin inherited disorders, among the most common genetic diseases in the world, frequent in the Mediterranean basin. As beta-thalassemia patients' survival has increased over time, previously unknown complications are observed with increasing frequency. Among them, an increased risk of hepatocellular carcinoma (HCC) has been registered. Our aim is to reduce inequalities in diagnosis and treatment and to offer patients univocal recommendations in any institution. The members of the panel - gastroenterologists, radiologists, surgeons and oncologists -were selected on the basis of their publication records and expertise. Thirteen clinical questions, derived from clinical needs, and an integration of all the committee members' suggestions, were formulated. Modified Delphi approach involving a detailed literature review and the collective judgement of experts, was applied to this work. Thirteen statements were derived from expert opinions' based on the current literature, on recently developed reviews and on technological advancements. Each statement is discussed in a short paragraph reporting the current key evidence. As this is an emerging issue, the number of papers on HCC in beta-thalassemia patients is limited and based on anecdotal cases rather than on randomized controlled studies. Therefore, the panel has discussed, step by step, the possible differences between beta-thalassemia and non beta-thalassemia patients. Despite the paucity of the literature, practical and concise statements were generated. This paper offers a practical guide organized by statements describing how to manage HCC in patients with beta-thalassemia

Radiogenomics in clear cell renal cell carcinoma: correlations between advanced CT imaging (texture analysis) and microRNAs expression

Purpose: A relevant challenge for the improvement of clear cell renal cell carcinoma management could derive from the identification of novel molecular biomarkers that could greatly improve the diagnosis, prognosis, and treatment choice of these neoplasms. In this study, we investigate whether quantitative parameters obtained from computed tomography texture analysis may correlate with the expression of selected oncogenic microRNAs. Methods: In a retrospective single-center study, multiphasic computed tomography examination (with arterial, portal, and urographic phases) was performed on 20 patients with clear cell renal cell carcinoma and computed tomography texture analysis parameters such as entropy, kurtosis, skewness, mean, and standard deviation of pixel distribution were measured using multiple filter settings. These quantitative data were correlated with the expression of selected microRNAs (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both the evaluations (microRNAs and computed tomography texture analysis) were performed on matched tumor and normal corticomedullar tissues of the same patients cohort. Results: In this pilot study, we evidenced that computed tomography texture analysis has robust parameters (eg, entropy, mean, standard deviation) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression was evidenced in tumor versus normal tissue. Interestingly, entropy and miR-21-5p show promising correlation in clear cell renal cell carcinoma opening to a radiogenomic strategy to improve clear cell renal cell carcinoma management. Conclusion: In this pilot study, a promising correlation between microRNAs and computed tomography texture analysis has been found in clear cell renal cell carcinoma. A clear cell renal cell carcinoma can benefit from noninvasive evaluation of texture parameters in adjunction to biopsy results. In particular, a promising correlation between entropy and miR-21-5p was found

Unusual sub-genus associations of fecal Prevotella and Bacteroides with specific dietary patterns

Background: Diet has a recognized effect in shaping gut microbiota. Many studies link an increase in Prevotella to high-fibre diet, while Bacteroides abundance is usually associated with the consumption of animal fat and protein-rich diets. Nevertheless, closely related species and strains may harbour different genetic pools; therefore, further studies should aim to understand whether species of the same genus are consistently linked to dietary patterns or equally responsive to diet variations. Here, we used oligotyping of 16S rRNA gene sequencing data to exploit the diversity within Prevotella and Bacteroides genera in faecal samples of omnivore and non-omnivore subjects from a previously studied cohort. Results: A great heterogeneity was found in oligotype composition. Nevertheless, different oligotypes within the same genus showed distinctive correlation patterns with dietary components and metabolome. We found that some Prevotella oligotypes are significantly associated with the plant-based diet but some are associated with animal-based nutrients, and the same applies to Bacteroides. Therefore, an indiscriminate association of Bacteroidetes genera with specific dietary patterns may lead to an oversimplified vision that does not take into account sub-genus diversity and the different possible responses to dietary components. Conclusions: We demonstrated that Prevotella and Bacteroides oligotypes show distinctive correlation patterns with dietary components and metabolome. These results substantiate a current oversimplification of diet-dependent microbe-host associations and highlighted that sub-genus differences must be taken into account when planning gut microbiota modulation for health benefits

Dynamic MR of the pelvic floor. Influence of alternative methods to draw the pubococcygeal line (PCL) on the grading of pelvic floor descent

Objective: To evaluate the impact of the pubococcygeal line (PCL) position on hiatal descent grading, comparing the method recommended by the official guidelines with the other two most common methods reported in literature. Methods: Female patients prospectively included performed dynamic-MR (1,5 T) in supine position. Rectum and vagina were filled with ultrasound gel. MR protocol included TSE T2 weighted sequences on axial/sagittal/coronal planes and steady-state sequences (FIESTA) on midsagittal plane during three phases (rest, strain and defecation). On each phase, the posterior point of PCL was traced in the region recommended by the official guidelines (last coccygeal joint or PCLcc) and in the other two regions: coccyx's tip (PCLtip) and sacrococcygeal joint (PCLsc). The resulting grades of pelvic floor descent (according to HMO-System) were compared. Inter-reader and intra-reader agreement were evaluated. Results: The final population consisted of 60 patients (56yy±10). No significant differences in grading were observed using PCLtip and PCLcc in all phases (p = 0.3016/0.0719/0.0719 during rest/strain/defecation). Using PCLsc, the grading was significantly overestimated compared to PCLcc in all phases (p = 0.0041/0.0001/0.0001 during rest/strain/defecation). Inter-reader and intra-reader agreement were significantly higher using PCLtip (p < 0.05). Conclusions: PCLtip is a reliable and highly reproducible option to the official PCLcc to correctly grade the pelvic floor descent and could be used when the PCLcc is not clearly visible. The use of PCLsc overestimates the grading compared to the official PCLcc and should not be used to avoid wrong patients’ management

A combined proteomics, metabolomics and in vivo analysis approach for the characterization of probiotics in large-scale production

The manufacturing processes of commercial probiotic strains may be affected in different ways in the attempt to optimize yield, costs, functionality, or stability, influencing gene expression, protein patterns, or metabolic output. Aim of this work is to compare different samples of a high concentration (450 billion bacteria) multispecies (8 strains) formulation produced at two different manufacturing sites, United States of America (US) and Italy (IT), by applying a combination of functional proteomics, metabolomics, and in vivo analyses. Several protein-profile differences were detected between IT-and US-made products, with Lactobacillus paracasei, Streptococcus thermophilus, and Bifidobacteria being the main affected probiotics/microorganisms. Performing proton nuclear magnetic spectroscopy (1H-NMR), some discrepancies in amino acid, lactate, betaine and sucrose concentrations were also reported between the two products. Finally, we investigated the health-promoting and antiaging effects of both products in the model organism Caenorhabditis elegans. The integration of omics platforms with in vivo analysis has emerged as a powerful tool to assess manufacturing procedures

The first joint ESGAR/ ESPR consensus statement on the technical performance of cross-sectional small bowel and colonic imaging

Objectives: To develop guidelines describing a standardised approach to patient preparation and acquisition protocols for magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US) of the small bowel and colon, with an emphasis on imaging inflammatory bowel disease. Methods: An expert consensus committee of 13 members from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and European Society of Paediatric Radiology (ESPR) undertook a six-stage modified Delphi process, including a detailed literature review, to create a series of consensus statements concerning patient preparation, imaging hardware and image acquisition protocols. Results: One hundred and fifty-seven statements were scored for agreement by the panel of which 129 statements (82 %) achieved immediate consensus with a further 19 (12 %) achieving consensus after appropriate modification. Nine (6 %) statements were rejected as consensus could not be reached. Conclusions: These expert consensus recommendations can be used to help guide cross-sectional radiological practice for imaging the small bowel and colon. Key points: • Cross-sectional imaging is increasingly used to evaluate the bowel • Image quality is paramount to achieving high diagnostic accuracy • Guidelines concerning patient preparation and image acquisition protocols are provided

Constraints on Kerr-Newman black holes from merger-ringdown gravitational-wave observations

We construct a template to model the post-merger phase of a binary black hole coalescence in the presence of a remnant $U(1)$ charge. We include the quasi-normal modes typically dominant during a binary black hole coalescence, $(\ell,m,n) = \{(2,2,0), (2,2,1)\}$ and also present analytical fits for the quasinormal mode frequencies of a Kerr-Newman black hole in terms of its spin and charge, here also including the $(3,3,0)$ mode. Aside from astrophysical electric charge, our template can accommodate extensions of the Standard Model, such as a dark photon. Applying the model to LIGO-Virgo detections, we find that we are unable to distinguish between the charged and uncharged hypotheses from a purely post-merger analysis of the current events. However, restricting the mass and spin to values compatible with the analysis of the full signal, we obtain a 90th percentile bound $\bar{q} < 0.33$ on the black hole charge-to-mass ratio, for the most favorable case of GW150914. Under similar assumptions, by simulating a typical loud signal observed by the LIGO-Virgo network at its design sensitivity, we assess that this model can provide a robust measurement of the charge-to-mass ratio only for values $\bar{q} \gtrsim 0.5$; here we also assume that the mode amplitudes are similar to the uncharged case in creating our simulated signal. Lower values, down to $\bar{q} \sim 0.3$, could instead be detected when evaluating the consistency of the pre-merger and post-merger emission.Comment: 21 pages, 11 figures, 4 tables. Matches published versio

Journey through crohn’s disease complication: From fistula formation to future therapies

Crohn’s Disease (CD) is a chronic inflammatory disorder in which up to 50% of patients develop fistula within 20 years after the initial diagnosis, and half of these patients suffer perianal fistulizing disease. The etiopathogenesis of CD-related perianal fistula is still unclear, and its phe-notypical and molecular characteristics are even more indefinite. A better understanding would be crucial to develop targeted and more effective therapeutic strategies. At present, the most accredited theory for the formation of CD-related fistula identifies the epithelial-to-mesenchymal transition (EMT) as the driving force. It has been well recognized that CD carries an increased risk of malig-nancy, particularly mucinous adenocarcinoma is often associated with long-standing fistula in CD patients. Despite the availability of multiple treatment options, perianal fistulizing CD represents a therapeutic challenge and is associated with an important impact on patients’ quality of life. To date, the most effective management is multidisciplinary with the cooperation of gastroenterologists, surgeons, radiologists, and nutritionists and the best recommended treatment is a combination of medical and surgical approaches