A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66–19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64–57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9–10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Geometry and field theory in multi-fractional spacetime

We construct a theory of fields living on continuous geometries with fractional Hausdorff and spectral dimensions, focussing on a flat background analogous to Minkowski spacetime. After reviewing the properties of fractional spaces with fixed dimension, presented in a companion paper, we generalize to a multi-fractional scenario inspired by multi-fractal geometry, where the dimension changes with the scale. This is related to the renormalization group properties of fractional field theories, illustrated by the example of a scalar field. Depending on the symmetries of the Lagrangian, one can define two models. In one of them, the effective dimension flows from 2 in the ultraviolet (UV) and geometry constrains the infrared limit to be four-dimensional. At the UV critical value, the model is rendered power-counting renormalizable. However, this is not the most fundamental regime. Compelling arguments of fractal geometry require an extension of the fractional action measure to complex order. In doing so, we obtain a hierarchy of scales characterizing different geometric regimes. At very small scales, discrete symmetries emerge and the notion of a continuous spacetime begins to blur, until one reaches a fundamental scale and an ultra-microscopic fractal structure. This fine hierarchy of geometries has implications for non-commutative theories and discrete quantum gravity. In the latter case, the present model can be viewed as a top-down realization of a quantum-discrete to classical-continuum transition.Comment: 1+82 pages, 1 figure, 2 tables. v2-3: discussions clarified and improved (especially section 4.5), typos corrected, references added; v4: further typos correcte

Correlation of Tc-99m-red blood cell phleboscintigraphy with clinical severity of chronic venous disease

Equilibrium red blood cell phleboscintigraphy of the lower limbs for the diagnostic management of chronic venous disease has been proposed. The aim of this study was to verify the correlation of the phleboscintigraphic assessment of chronic venous disease with the clinical grading of the severity of the disease, since other diagnostic modalities have been recently demonstrated a poor and only partial correlation. Equilibrium Tc-99m-red blood cell phleboscintigraphy was performed in 27 patients with chronic venous disease. Scintigraphic images of 52 limbs were classified according to a four-class qualitative grading of the severity of the venous disease, and a quantitative scintigraphic index (saphena /femoral ratio) was assigned to each limb. The scintigraphic qualitative grading showed a highly significant correlation with the clinical grading (Rs=0.82, p<0.01), a good interobserver and intraobserver agreement (86.5% and 92.3%, respectively) and more than 90% sensitivity and specificity to identify the categories "minimal or no chronic venous disease" or "more significant disease" (assessed according to the Bayes theorem). Sensitivity and specificity results for the quantitative assessment were not as good. Phleboscintigraphy correlates well with the clinical grading of the severity of chronic venous disease of the lower limbs and may have potential as a valuable diagnostic tool for the noninvasive assessment of chronic venous disease

Rhinoscintigraphy. A simple radioisotope technique to study the mucociliary system

Purpose: This was a radioisotope study of nasal mucociliary clearance of total and subtotal nasal obstruction. Methods: Rhinoscintigraphy was performed by insufflating 1.85 MBq (69 mCi) Tc- 99m MAA in 20 patients. Six cases were regarded as the control group, because the presence of small spurs does not affect nasal patency. The remaining 14 patients had various rhinopathic conditions. Two regions of interest were selected, one in the nasal cavity and one in the pharynx. Mucociliary transport speed was calculated. Results: This parameter appeared to be a sensitive index for the assessment of the degree of mucociliary alteration. It showed that polyposis impairs mucociliary transport most severely, thus confirming the results of other published studies. Conclusions: Rhinoscintigraphy proved to be a reliable, easily reproducible, and harmless method, so it may be used for follow-up examinations in patients who have had surgery of the nose and paranasal sinuses, and for drug therapy of rhinopathic conditions

Assessment of sympathetic innervation of the heart in diabetes mellitus using 123I-MIBG

Radio-labeled metaiodobenzylguanidine (MIBG) is considered an established sympathetic neuron imaging agent capable of scintigraphically visualizing the organs richly innervated by the sympathetic nervous system. Its clinical applications now include cardiac and pulmonary adrenergic imaging. The quantitative determination of global and/or regional abnormalities of MIBG heart uptake has been demonstrated to be very useful in several clinical settings representing one of the major determinants of adverse prognosis. The presence and the severity of autonomic neuropathy are known as important prognostic factors in patients with diabetes. MIBG scintigraphy is able to non-invasively assess and characterize the adrenergic abnormalities of the cardiac innervation also in these patients. In order to evaluate whether 123I-MIBG is able to reveal abnormalities of myocardial adrenergic function in different groups of diabetic patients, we performed 123I-MIBG scintigraphy in control subjects and in normotensive Type 1 diabetic patients with and without autonomic neuropathy (N+ and N- patients), selected according to results of cardiovascular reflex tests, Regional abnormalities of adrenergic innervation were revealed in 10% of control subjects, in 70% of N- patients and in 100% of N+ patients. The finding of a higher than expected prevalence of MIBG regional abnormalities in patients without signs or symptoms of autonomic neuropathy allows to hypothesize that cardiac autonomic nervous damage occurs earlier than previously known in diabetic patients whose cardiovascular tests are still completely normal. (C) 2000, Editrice Kurtis

Assessment of sympathetic innervation of the heart in diabetes mellitus using 123I-MIBG

Radio-labeled metaiodobenzylguanidine (MIBG) is considered an established sympathetic neuron imaging agent capable of scintigraphically visualizing the organs richly innervated by the sympathetic nervous system. Its clinical applications now include cardiac and pulmonary adrenergic imaging. The quantitative determination of global and/or regional abnormalities of MIBG heart uptake has been demonstrated to be very useful in several clinical settings representing one of the major determinants of adverse prognosis. The presence and the severity of autonomic neuropathy are known as important prognostic factors in patients with diabetes. MIBG scintigraphy is able to non-invasively assess and characterize the adrenergic abnormalities of the cardiac innervation also in these patients. In order to evaluate whether 123I-MIBG is able to reveal abnormalities of myocardial adrenergic function in different groups of diabetic patients, we performed 123I-MIBG scintigraphy in control subjects and in normotensive Type 1 diabetic patients with and without autonomic neuropathy (N+ and N- patients), selected according to results of cardiovascular reflex tests, Regional abnormalities of adrenergic innervation were revealed in 10% of control subjects, in 70% of N- patients and in 100% of N+ patients. The finding of a higher than expected prevalence of MIBG regional abnormalities in patients without signs or symptoms of autonomic neuropathy allows to hypothesize that cardiac autonomic nervous damage occurs earlier than previously known in diabetic patients whose cardiovascular tests are still completely normal. (C) 2000, Editrice Kurtis