P132 Uncovering blood biomarkers of Inflammatory Bowel Diseases by Raman spectroscopy and FAP dosage: toward a noninvasive triage of patients in first care diagnostic

Abstract Background Currently, a major point of concern in the management of Inflammatory Bowel Diseases (IBD) is the absence of accurate and specific circulating biomarkers able to drive diagnosis in a timely and noninvasive manner. Aim of the present study was to explore blood biomarkers of IBD by coupling the targeted detection of circulating fibroblast activation protein (FAP), a recognized valuable marker of bowel lesion in IBD, and Raman spectroscopy (RS), a quick and label-free metabolomic technique that provides a real-time biochemical characterization of plasma samples without any previously known target. Methods Blood samples were collected from over 140 patients with IBD and 170 control subjects matched for gender and age. Isolated plasma was analysed by enzyme-linked immunosorbent assay for quantitative detection of circulating form of FAP. RS was performed on dry droplets of plasma, with the aim to decipher specific fingerprint of IBD in peripheral blood. A predictive model was built on FAP and Raman data separately, to determine specificity, sensitivity and accuracy of the two approaches in patients classification. Supervised multivariate model was applied on a subset of 203 patients to discriminate IBD and control subjects based on combined datasets. Results FAP levels were reduced in patients with IBD as compared to controls (p<0.0001). The sensitivity and specificity of FAP were 70% and 84% based on the optimal cutoff (57.6 ng mL-1, AUC=0.78). Raman spectra of IBD plasma revealed significant differences in peaks corresponding to carotenoids, proteins with β-sheet secondary structure, lipids and aromatic amino-acids. A machine learning model was applied on a subset of patients reaching an accuracy of 85% in classifying IBD and control subjects. No statistically significant differences were observed so far between the discriminative performance of the sole RS or the combination of RS and FAP. Conclusion RS and FAP dosage enable new discoveries in the biological fingerprint of IBD plasma and provide novel candidate biomarkers of IBD. Our preliminary results strongly suggest that novel blood-based approaches could represent a fast noninvasive way to triage patents with suspected IBD in first care diagnostic, to be applied prior to further specific evaluation

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients

Background: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. Patients and methods: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). Results: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75\u20130.80). After external validation the accuracy of the nomogram was confirmed. Conclusion: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients

Low neutrophil-to-lymphocyte ratio and pan-immune-inflammation-value predict nodal pathologic complete response in 1274 breast cancer patients treated with neoadjuvant chemotherapy: a multicenter analysis

Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings. Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients. Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units. Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR. Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51–0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44–0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients (n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)−/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12–0.83; p = 0.02) and ER−/HER2− (OR = 0.41; 95% CI, 0.17–0.97; p = 0.04) BC patients. Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC. Registration: Eudract number NCT05798806

Whole body vibration: What is all the fuss about?

Whole body vibration (WBV) has been promoted in the market as a new method for exercising, by which 10min are more than enough for the fitness training of busy, modern people. Several companies have been over-stating the positive effects that this type of exercise has on the human body, advertising the general improvement in strength, flexibility and neuromuscular performance granted through it. The question needs to be asked: ‘Does WBV do what it is said to be doing?’. © 2010, MA Healthcare Ltd. All rights reserved

Theoretical and experimental study of flavones as inhibitors of xanthine oxidase

Inhibitory activities of 19 polyhydroxylated and polymethoxylated flavones towards xanthine oxidase have been obtained by accurate measurements of the dissociation constants of enzyme-inhibitor complexes (K-EI). A topological description of the congeneric series has been adopted to derive quantitative structure-activity relationships (QSAR) with the use of multiple linear regression analysis. For interpretative purposes, molecular orbital calculations have also been performed. Inhibition appears to involve flavones as donors and the anion at the C-7 hydroxyl as the most active form in solution. Substituents in the 4H-1-benzopyran-4-one moiety can directly affect the availability of the C-7 anion in solution; substituents in the 2-phenyl moiety are probably involved in secondary local interactions with the enzyme

Physico-chemical properties of anthocyanidins. Part 1. Theoretical evaluation of the stability of the neutral and anionic tautomeric forms

Quantum chemical (AM1) and solvation model calculations have been applied to the study of tautomeric stabilities in three anthocyanidins, so as to single out the dominant tautomeric forms (neutral and anionic) at physiological pH. The theoretical information concerning the tautomeric stabilities and electronic structures of anthocyanidins are essential for the development of quantitative structure-activity relationships. The present results allow us to discriminate between the wide variety of tautomeric forms, and to infer that, depending on the pH, only two neutral tautomers and two anionic tautomers should be present in solution. On interpretative grounds, the main factors determining stability are chiefly ascribable to the extent of pi-electron delocalization and to the possibility of classical resonance structures. Several theoretical descriptors have been calculated for use in quantitative structure-activity relationships

A rational approach to the design of flavones as xanthine oxidase inhibitors

In the light of previous QSAR studies on flavones as inhibitors of xanthine oxidase, we synthesized and tested a new series of 7-hydroxyflavones carrying a wide and balanced variety of substituents (pi, sigma(p)) at the 4' position in order to explore the effect of substituents at this position on the xanthine oxidase inhibitory activity. The results of pK(a) determinations show that the electronic effects of the substituents are not transferred to the hydroxyl at C7, previously found to be fundamental for activity. An excellent correlation is found between molar refractivity of the substituents and the inhibitory activity. These results, applied to the more active 5,7-dihydroxyflavones, allowed the design and synthesis of a very active inhibitor, with an IC50 in the nanomolar range. On interpretative grounds, C4' substituents of flavones are involved in dispersion interactions with the enzyme. The calculation of quantum chemical polarizabilities and solvent accessible surface areas suggests the existence of pi-pi stacking interactions with an aromatic aminoacidic residue of the enzyme