Search

Aim To study the feasibility of radiomic analysis of baseline [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT) for the prediction of biochemical recurrence (BCR) in a cohort of intermediate and high-risk prostate cancer (PCa) patients. Material and methods Seventy-four patients were prospectively collected. We analyzed three prostate gland (PG) segmentations (i.e., PGwhole: whole PG; PG41%: prostate having standardized uptake value – SUV > 0.41*SUVmax; PG2.5: prostate having SUV > 2.5) together with three SUV discretization steps (i.e., 0.2, 0.4, and 0.6). For each segmentation/discretization step, we trained a logistic regression model to predict BCR using radiomic and/or clinical features. Results The median baseline prostate-specific antigen was 11 ng/mL, the Gleason score was > 7 for 54% of patients, and the clinical stage was T1/T2 for 89% and T3 for 9% of patients. The baseline clinical model achieved an area under the receiver operating characteristic curve (AUC) of 0.73. Performances improved when clinical data were combined with radiomic features, in particular for PG2.5 and 0.4 discretization, for which the median test AUC was 0.78. Conclusion Radiomics reinforces clinical parameters in predicting BCR in intermediate and high-risk PCa patients. These first data strongly encourage further investigations on the use of radiomic analysis to identify patients at risk of BCR. Clinical relevance statement The application of AI combined with radiomic analysis of [18F]fluoromethylcholine PET/CT images has proven to be a promising tool to stratify patients with intermediate or high-risk PCa in order to predict biochemical recurrence and tailor the best treatment options. Key Points • Stratification of patients with intermediate and high-risk prostate cancer at risk of biochemical recurrence before initial treatment would help determine the optimal curative strategy. • Artificial intelligence combined with radiomic analysis of [18F]fluorocholine PET/CT images allows prediction of biochemical recurrence, especially when radiomic features are complemented with patients’ clinical information (highest median AUC of 0.78). • Radiomics reinforces the information of conventional clinical parameters (i.e., Gleason score and initial prostate-specific antigen level) in predicting biochemical recurrence.

An unnecessary amount of complexity in radiotherapy plans affects the efficiency of the treatments, increasing the uncertainty of dose deposition and its susceptibility to anatomical changes or setup errors. To date, tools for quantitatively assessing the complexity of tomotherapy plans are still limited. In this study, new metrics were developed to characterize different aspects of helical tomotherapy (HT) plans, and their actual effectiveness was investigated.The complexity of 464 HT plans delivered on a Radixact platform was evaluated. A new set of metrics was devised to assess beam geometry, leaf opening time (LOT) variability, and modulation over space and time. Sixty-five complexity metrics were extracted from the dataset using the newly in-house developed software library TCoMX: 29 metrics already proposed in the literature and 36 newly developed metrics. Their reciprocal relation is discussed. Their effectiveness was evaluated through correlation analyses with patient-specific quality assurance (PSQA) results.An inverse linear relation was found between the average number of closed leaves and the average number of MLC openings and closures as well as between the choice of the modulation factor and the discontinuity of the field, suggesting some intrinsic link between the LOT distribution and the geometrical complexity of the MLC openings. The newly proposed metrics were at least as correlated as the existing ones to the PSQA results. Metrics describing the geometrical complexity of the MLC openings showed the strongest connection to the PSQA results. Significant correlations were found between at least one of the new metrics and the γ index passing rateThe new metrics proposed were shown to be effective to characterize more comprehensively the complexity of HT plans. A software library for their automatic extraction is described and made available.

Objective: To assess if photobiomodulation (PBM) improves the efficiency of orthodontic treatment with fixed appliance during the alignment stage. Methods: Eighty-nine subjects were included in this trial and randomly assigned for treatment with fixed appliance and PBM group or with fixed appliance only (control group). Inclusion criteria were as follows: (1) age between 13 and 30 years, (2) permanent dentition, (3) class I malocclusion, (4) lower 6-6 mild crowding measured on dental cast, (5) no spaces or diastema in the lower arch, (6) no ectopic teeth, (7) nonextractive treatment plan, and (8) no previous orthodontic treatment. PBM was administered in the PBM group every 14 days using the ATP38® (Biotech Dental, Allée de Craponne, Salon de Provence, France) (72 J/cm2 of fluency for each session). Dental alignment was assessed by visual inspection, and treatment time was defined in days as T2 (date of assessment of complete dental alignment)-T1 (date of brackets bonding). The number of monthly scheduled appointments was also recorded. All the data underwent statistical analysis for comparison between groups. Results: Treatment time was significantly shorter (p < 0.001) in the PBM group (203 days) compared with the control (260 days). Consequently, control visits (p < 0.001) were lower in the PBM group (7) compared with the control group (9). Conclusions: The present findings would confirm that PBM can be used to enhance the efficiency of orthodontic treatment during dental decrowding.

Introduction: The treatment of a true unilateral posterior crossbite often requires asymmetric maxillary expansion; however, this is challenging to achieve with conventional expansion methods because of several biomechanical limitations. In this paper, we introduce a new protocol for the treatment of a unilateral posterior crossbite in adults based on maxillary orthodontic expansion assisted by corticotomy and low-level laser therapy (LLLT) performed on the crossbite side. Methods: The study sample included 15 adults (8 females, 7 males) affected by a true unilateral posterior crossbite, with a mean age of 21.6 ± 3.1 years at the at the beginning of treatment. After the application of orthodontic appliances (palatal expander and self-ligating brackets), corticomy was performed at the buccal aspect of the crossbite side while LLLT was monthly administered up to the correction of the crossbite. The efficacy of the technique was evaluated through measurements performed on maxillary digital models. Results: All subjects reported successful correction of the posterior unilateral crossbite, and functional occlusion was achieved as well. The average expansion was greater at the crossbite side compared to the unaffected side and such difference was significant at the levels of first premolars (P < 0.05), second premolars (P < 0.05) and first molars (P < 0.05). Conclusion: Orthodontic maxillary expansion assisted by unilateral corticotomy and LLLT was effective in the treatment of the true unilateral crossbite.

In radiology and oncology, radiomic models are increasingly employed to predict clinical outcomes, but their clinical deployment has been hampered by lack of standardisation. This hindrance has driven the international Image Biomarker Standardisation Initiative (IBSI) to define guidelines for image pre-processing, standardise the formulation and nomenclature of 169 radiomic features and share two benchmark digital phantoms for software calibration. However, to better assess the concordance of radiomic tools, more heterogeneous phantoms are needed. We created two digital phantoms, called ImSURE phantoms, having isotropic and anisotropic voxel size, respectively, and 90 regions of interest (ROIs) each. To use these phantoms, we designed a systematic feature extraction workflow including 919 different feature values (obtained from the 169 IBSI-standardised features considering all possible combinations of feature aggregation and intensity discretisation methods). The ImSURE phantoms will allow to assess the concordance of radiomic software depending on interpolation, discretisation and aggregation methods, as well as on ROI volume and shape. Eventually, we provide the feature values extracted from these phantoms using five open-source IBSI-compliant software.

BackgroundPubertal development is a complex process influenced by a multitude of factors; among these, the role of melatonin has only been partially investigated. During the COVID-19 pandemic an unexpected increase in cases of precocious and fast puberty was observed.AimsTo evaluate the possible role of salivary melatonin in precocious and accelerated puberty during the COVID-19 lockdown.Patients and MethodsFifty-four females were evaluated from October 2020 to March 2021; of these, 39 children were diagnosed with central precocious puberty (CPP) and 15 with isolated premature thelarche (IPT). Thirty-three healthy children acted as controls. The enrolled patients were asked to take measures the day before the visit to avoid influencing readings of melatonin secretion. Salivary melatonin levels were analyzed using commercially available ELISA kit.ResultsThere was no difference in the time from B2 to diagnosis (months) between IPT and CPP patients. However, the anamnestic and clinical data of our CPP patients confirmed an acceleration in the stages of pubertal development. As expected, subjects with CPP showed a significantly greater stature SDS and height velocity SDS. There were no differences in BMI SDS and Delta BMI SDS. Interestingly, we discovered a significant difference regarding the use of electronic devices between children with CPP, IPT and controls (p

Purpose Technetium-99m (99m Tc) is the radioisotope most widely used in diagnostic nuclear medicine. It is readily available from 99 Mo/99m Tc generators as the β- decay product of the 99 Mo (Tf = 66 h) parent nuclide. This latter is obtained as a fission product in nuclear reactors by neutron-induced reactions on highly enriched uranium. Alternative production routes, such as direct reactions using proton beams on specific target materials [100 Mo(p,2n)99m Tc], have the potential to be both reliable and relatively cost-effective. However, results showed that the 99m Tc extracted from proton-bombarded 100 Mo-enriched targets contains small quantities of several Tc radioisotopes (93m Tc, 93 Tc, 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96 Tc, and 97m Tc). The aim of this work was to estimate the dose increase (DI) due to the contribution of Tc radioisotopes generated as impurities, after the intravenous injection of four radiopharmaceuticals prepared with cyclotron-produced 99m Tc (CP-99m Tc) using 99.05% 100 Mo-enriched metallic targets. Methods Four 99m Tc radiopharmaceuticals (pertechnetate, sestamibi (MIBI), hexamethylpropylene-amine oxime (HMPAO) and disodium etidronate (HEDP)) were considered in this study. The biokinetic models reported by the International Commission on Radiological Protection (ICRP) for each radiopharmaceutical were used to define the main source organs and to calculate the number of disintegrations per MBq that occurred in each source organ (Nsource ) for each Tc radioisotope present in the CP-99m Tc solution. Then, target organ equivalent doses and effective dose were calculated for each Tc radioisotope with the OLINDA/EXM software versions 1.1 and 2.0, using the calculated Nsource values and the adult male phantom as program inputs. Total effective dose produced by all Tc isotopes impurities present in the CP-99m Tc solution was calculated using the fraction of total activity corresponding to each radioisotope and compared with the effective dose delivered by the generator-produced 99m Tc. Results In all cases, the total effective DI of CP-99m Tc radiopharmaceuticals calculated with either versions of the OLINDA software was less than 10% from 6 up to 12 h after EOB. 94m Tc and 93m Tc are the Tc radioisotopes with the highest concentration in the CP-99m Tc solution at EOB. However, their contribution to DI 6 h after EOB is minimal, due to their short half-lives. The radioisotopes with the largest contribution to the effective DI are 96 Tc, followed by 95 Tc and 94 Tc. This is due to the types of their emissions and relatively long half-lives, although their concentration in the CP-99m Tc solution is five times lower than that of 94m Tc and 93m Tc at the EOB. Conclusions The increase in the radiation dose caused by other Tc radioisotopes contained in CP-99m Tc produced as described here is quite low. Even though the concentrations of the 94 Tc and 95 Tc radioisotopes in the CP-99m Tc solution exceed the limits established by the European Pharmacopoeia, CP-99m Tc radiopharmaceuticals could be used in routine nuclear medicine diagnostic studies if administered from 6 to 12 h after the EOB, thus maintaining the effective DI within the 10% limit.

Background The translation of radiomic models into clinical practice is hindered by the limited reproducibility of features across software and studies. Standardization is needed to accelerate this process and to bring radiomics closer to clinical deployment. Purpose To assess the standardization level of seven radiomic software programs and investigate software agreement as a function of built-in image preprocessing (eg, interpolation and discretization), feature aggregation methods, and the morphological characteristics (ie, volume and shape) of the region of interest (ROI). Materials and Methods The study was organized into two phases: In phase I, the two Image Biomarker Standardization Initiative (IBSI) phantoms were used to evaluate the IBSI compliance of seven software programs. In phase II, the reproducibility of all IBSI-standardized radiomic features across tools was assessed with two custom Italian multicenter Shared Understanding of Radiomic Extractors (ImSURE) digital phantoms that allowed, in conjunction with a systematic feature extraction, observations on whether and how feature matches between program pairs varied depending on the preprocessing steps, aggregation methods, and ROI characteristics. Results In phase I, the software programs showed different levels of completeness (ie, the number of computable IBSI benchmark values). However, the IBSI-compliance assessment revealed that they were all standardized in terms of feature implementation. When considering additional preprocessing steps, for each individual program, match percentages fell by up to 30%. In phase II, the ImSURE phantoms showed that software agreement was dependent on discretization and aggregation as well as on ROI shape and volume factors. Conclusion The agreement of radiomic software varied in relation to factors that had already been standardized (eg, interpolation and discretization methods) and factors that need standardization. Both dependences must be resolved to ensure the reproducibility of radiomic features and to pave the way toward the clinical adoption of radiomic models. Published under a CC BY 4.0 license.

The aim of this research is investigating nullum crimen sine lege as European principle. Therefore, the analysis focuses on the European Court of Human Rights (ECtHR) interpretation of this principle. The approach of this work is top-down. Since the research question is the role of foreseeability assessment in ?Europeanised? Criminal Law and its possible relevance at the European and national level, when and if necessary, the chosen approach is to look first at the European perspective, in order to analyse it in depth in its own specificities and then try to link it to the national perspective. With regards to ECHR law, the autonomous definition of law and the application of foreseeability (one of the ?qualities? of the law) as main parameter to assess legality, both in light of retroactivity and legal certainty, are investigated. In particular, special attention is given to the role of judge-made law in the interpretation of Art. 7 ECHR. Hence, the research focuses on the role of foreseeability, milestone of European legality, as a means to find a solution to the legality issues raising from judge-made law in criminal law. The origin, rationale and application of the concept of foreseeability in ECtHR case-law are scrutinised, trying to extract its main development paths. Subsequently, the current solutions that civil law States adopt to try solving the problem of case-law in criminal law are analysed, with reference to Italy and Germany, also with regards to the traditional rationales of nullum crimen and its theoretical foundations. Moreover, the role of foreseeability and legality in the European Union legal order is considered, as an example of an effectiveness-oriented and de-formalised legal order. In the end, future perspectives for the implementation of the principle of foreseeability are analysed, with particular regard to the Italian legal order.

Simple Summary Prostate cancer (PCa) is one of the most frequent malignancies diagnosed in men and its prognosis depends on the stage at diagnosis. Molecular imaging, namely PET/CT or PET/MRI using prostate-specific radiotracers, has gained increasing application in accurately evaluating PCa at staging, especially in cases of high-risk disease, and it is now also recommended by international guidelines. Radiomic analysis is an emerging research field with a high potential to offer non-invasive and longitudinal biomarkers for personalized medicine, and several applications have been described in oncology patients. In this review, we discuss the available evidence on the role of radiomic analysis in PCa imaging at staging, exploring two different hybrid imaging modalities, such as PET/CT and PET/MRI, and the whole spectrum of radiotracers involved. Abstract We performed a systematic review of the literature to provide an overview of the application of PET radiomics for the prediction of the initial staging of prostate cancer (PCa), and to discuss the additional value of radiomic features over clinical data. The most relevant databases and web sources were interrogated by using the query “prostate AND radiomic* AND PET”. English-language original articles published before July 2021 were considered. A total of 28 studies were screened for eligibility and 6 of them met the inclusion criteria and were, therefore, included for further analysis. All studies were based on human patients. The average number of patients included in the studies was 72 (range 52–101), and the average number of high-order features calculated per study was 167 (range 50–480). The radiotracers used were [68Ga]Ga-PSMA-11 (in four out of six studies), [18F]DCFPyL (one out of six studies), and [11C]Choline (one out of six studies). Considering the imaging modality, three out of six studies used a PET/CT scanner and the other half a PET/MRI tomograph. Heterogeneous results were reported regarding radiomic methods (e.g., segmentation modality) and considered features. The studies reported several predictive markers including first-, second-, and high-order features, such as “kurtosis”, “grey-level uniformity”, and “HLL wavelet mean”, respectively, as well as PET-based metabolic parameters. The strengths and weaknesses of PET radiomics in this setting of disease will be largely discussed and a critical analysis of the available data will be reported. In our review, radiomic analysis proved to add useful information for lesion detection and the prediction of tumor grading of prostatic lesions, even when they were missed at visual qualitative assessment due to their small size; furthermore, PET radiomics could play a synergistic role with the mpMRI radiomic features in lesion evaluation. The most common limitations of the studies were the small sample size, retrospective design, lack of validation on external datasets, and unavailability of univocal cut-off values for the selected radiomic features.

Purpose A recently introduced commercial tool is tested to assess whether it is able to reduce the complexity of a treatment plan and improve deliverability without compromising overall quality. Methods Ten prostate and ten oropharynx plans of previously treated patients were reoptimized using the aperture shape controller (ASC) tool recently introduced in Eclipse TPS (Varian Medical Systems, Palo Alto, CA). The performance of ASC was assessed in terms of the overall plan quality using a plan quality metric, the reduction in plan complexity through the analysis of 14 of the most common plan complexity metrics, and the change in plan deliverability through 3D dosimetric measurements. Similarly, plans optimized limiting the total number of delivered monitor units was assessed and compared. The two strategies were also combined to assess their potential combination. Results The plans optimized by exploiting the ASC generally show a reduced number of total Monitor Units, a more constant gantry rotation and a MLC modulation characterized by larger and less complicated shapes with leaves traveling shorter overall lengths. Conclusions This first experience suggests that the ASC is an effective tool to reduce the unnecessary complexity of a plan. This turns into an increased plan deliverability with no loss of plan quality.

Aim. In periodontology lasers have been suggested for the photodynamic therapy (PDT): such therapy can be defined as the inactivation of cells, microorganisms, or molecules induced by light and not by heat. The aim of this study was to evaluate results of PDT using a 980 nm diode laser (Wiser Doctor Smile, Lambda SPA, Italy) combined with hydrogen peroxide, comparing a pulsed diode laser (LI) activity to a high-frequency superpulsed diode laser (LII).Materials and Methods. Primary fibroblasts and keratinocytes cell lines, isolated from human dermis, were irradiated every 48 h for 10 days using LI and LII combined with SiOxyL+™Solution (hydrogen peroxide (HP) stabilized with a glycerol phosphate complex). Two days after the last irradiation, the treated cultures were analyzed by flow cytofluorometry (FACS) and western blotting to quantify keratin 5 and keratin 8 with monoclonal antibodies reactive to cytokeratin 5 and cytokeratin 8. Antimicrobial activity was also evaluated.Results. Both experimental models show the superiority of LII against LI. In parallel, stabilized HP provided better results in the regeneration test in respect to common HP, while the biocidal activity remains comparable.Conclusion. The use of high-frequency lasers combined with stabilized hydrogen peroxide can provide optimal results for a substantial decrease of bacterial count combined with a maximal biostimulation induction of soft tissues and osteogenesis.