Artificial intelligence techniques support nuclear medicine modalities to improve the diagnosis of Parkinson's disease and Parkinsonian syndromes

Abstract Purpose The aim of this review is to discuss the most significant contributions about the role of Artificial Intelligence (AI) techniques to support the diagnosis of movement disorders through nuclear medicine modalities. Methods The work is based on a selection of papers available on PubMed, Scopus and Web of Sciences. Articles not written in English were not considered in this study. Results Many papers are available concerning the increasing contribution of machine learning techniques to classify Parkinson's disease (PD), Parkinsonian syndromes and Essential Tremor (ET) using data derived from brain SPECT with dopamine transporter radiopharmaceuticals. Other papers investigate by AI techniques data obtained by 123I-MIBG myocardial scintigraphy to differentially diagnose PD and other Parkinsonian syndromes. Conclusion The recent literature provides strong evidence that AI techniques can play a fundamental role in the diagnosis of movement disorders by means of nuclear medicine modalities, therefore paving the way towards personalized medicine

Surgical Treatment of Angio‐Behçet

Patients with Behçet’s disease are at risk for multiple vessel‐related complications including thromboses, stenoses, occlusions, and aneurysms. Surgical treatment of Angio‐Behçet brings numerous challenges due to the peculiarities of the disease process and the high rate of complications. Recurrent vascular episodes are also quite common and Behçet patients require rigorous follow‐up. In this review, we focus on the manifestations of Behçet’s disease involving the venous system and the systemic arterial vasculitis focusing on the indications, workup, and techniques for surgical treatment. Several case studies from our own experience are presented together with supporting diagnostic imaging and the decision process whether to intervene is discussed. Although open surgery remains a valid option, new endovascular techniques are rapidly advancing and offer excellent results with important decrease in morbidity and mortality even in highly compromised patients

Design, synthesis and biological evaluation of 1,5-disubstituted α-amino tetrazole derivatives as non-covalent inflammasome-caspase-1 complex inhibitors with potential application against immune and inflammatory disorders

Compounds targeting the inflammasome-caspase-1 pathway could be of use for the treatment of inflammation and inflammatory diseases. Previous caspase-1 inhibitors were in great majority covalent inhibitors and failed in clinical trials. Using a mixed modelling, computational screening, synthesis and in vitro testing approach, we identified a novel class of non-covalent caspase-1 non cytotoxic inhibitors which are able to inhibit IL-1β release in activated macrophages in the low μM range, in line with the best activities observed for the known covalent inhibitors. Our compounds could form the basis of further optimization towards potent drugs for the treatment of inflammation and inflammatory disorders including also dysregulated inflammation in Covid 19

Photoelectrochemical abatement of arsenic in water by hematite photoelectrodes

Arsenic is considered as one of the major issues among drinkable water pollutants because of its widespread distribution and its low acceptable limits. The most widely used removal technology involves arsenic adsorption on iron oxides, but this process is more effective for As(V). Since in groundwater arsenic is usually present as As(III), a preliminary oxidation treatment is often required to get high abatement yields. Moreover, despite it is a cheap and effective technology, adsorption generates a contaminated bed that must be disposed as toxic waste or regenerated by expensive techniques. Aiming at solving such problems, we are developing an alternative process involving a one-pot photoelectrochemical in situ oxidation and adsorption. Hematite nanostructured photoelectrodes showed promising performances by achieving almost complete abatement of arsenic from aqueous solutions under simulated solar light irradiation, in the view of economic and environmental sustainable application

Role of Functional Neuroimaging with 123I-MIBG and 123I-FP-CIT in De Novo Parkinson's Disease: A Multicenter Study

Background: Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8-18 per 100,000 people per year and 0.3-1%, respectively. As parkinsonian symptoms do not appear until approximately 50-60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. Methods: 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. Results: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). Conclusions: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease

Photoelectrocatalytic oxidation of As(III) over hematite photoanodes: a sensible indicator of the presence of highly reactive surface sites

Hematite-based photoanodes were used for the photoelectrocatalysed batch oxidation of As(III) in water at pH 7 and 10. Tests were carried out at different As(III) initial concentrations, ranging from 150 g/L to 30 mg/L. With no pre-treatments, an initial inactive period of 40-50 minutes was always observed at the beginning of every test. This initial inactive period is completely removed by a surface modification of surface active sites induced by a pre-polarisation at 800 mV (vs. Ag/AgCl). The water splitting active sites related to the Fe(III)-Fe(IV) redox couple were proved to be not active towards As(III) oxidation. The modifications induced by the anodic prepolarisation were deeply studied: no evidence of the formation of surface highly oxidized iron sites (Fe(V) or Fe(VI) ) and/or of highly reactive oxygen vacant sites emerges from XPS analysis. Rather, all collected charaterisation data support the conclusion that more reactive terminal oxygen species are necessary for As(III) oxydation. The As(III) abatement reaction was modelled by two subsequent first order kinetics in As(III), independently from the initial As(III) concentration: this behavior was explained suggesting that the highly reactive sites, being formed after prepolarisation, are gradually depleted during the reaction. As this reaction was proved to be very sensitive to the presence of highly reactive iron sites, its utilization as a probe reaction to study hematite photoanodes is suggested

Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging

Colorectal cancer (CRC) is a leading tumor worldwide. In CRC, the angiogenic pathway plays a crucial role in cancer development and the process of metastasis. Thus, anti-angiogenic drugs represent a milestone for metastatic CRC (mCRC) treatment and lead to significant improvement of clinical outcomes. Nevertheless, not all patients respond to treatment and some develop resistance. Therefore, the identification of predictive factors able to predict response to angiogenesis pathway blockade is required in order to identify the best candidates to receive these agents. Unfortunately, no predictive biomarkers have been prospectively validated to date. Over the years, research has focused on biologic factors such as genetic polymorphisms, circulating biomarkers, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and microRNA. Moreover, research efforts have evaluated the potential correlation of molecular biomarkers with imaging techniques used for tumor assessment as well as the application of imaging tools in clinical practice. In addition to functional imaging, radiomics, a relatively newer technique, shows real promise in the setting of correlating molecular medicine to radiological phenotypes

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Conception et développement de membranes bipolaires avec interface tridimensionnelle

L'objectif de cette thèse était le développement de membranes bipolaires avec une interface conçue pour les applications de piles à combustible et d'électrolyse. Différentes méthodes ont été adoptées pour développer l'architecture de membranes bipolaires. La couche d'échange cationique (CEL) a été préparée par incorporation d’un réseau de nanofibres de polymère dans une matrice d'échange ionique. La couche d'échange anionique (AEL) a été préparée par pulvérisation. Cette approche permet d'améliorer la stabilité mécanique et d'ajuster l'épaisseur de la couche d'échange anionique et de diminuer la résistance électrique totale de la membrane bipolaire. L'électrofilage est le processus clé pour préparer la région d'interface avec une architecture en trois-dimensions (3D) composée de fibre échangeuses d'anions et de cations. Un catalyseur pour la dissociation de l'eau a été ajouté à la jonction 3D pour des applications faisant intervenir la dissociation de l’eau : électrodialyse, électrolyse, co-électrolyse de CO2/H2O. La CEL, l'AEL et la jonction 3D ont été caractérisées et la préparation de membranes bipolaires avec différentes régions d'interface a été réalisée. La résistance ionique des membranes bipolaires avec des couches d'épaisseur différente a été mesurée. La contribution de chaque couche à la résistance totale de la membrane a été évaluée, paramètre d'importance significative lors de la conception d'une membrane bipolaire. Une étude menée sur la caractérisation électrochimique des membranes bipolaires a mise en évidence l'importance du prétraitement par échange d'ions. L'interface bipolaire tridimensionnelle s'est avérée appropriée pour les piles à combustible et pour incorporer des catalyseurs de dissociation de l'eau pour les applications dans des dispositifs tels que les électrolyseurs.The objective of this PhD work was the development of bipolar membranes with engineered interface region for fuel cell and electrolysis applications. Different methods were adopted to develop the architecture of the bipolar membranes. The cation exchange layer (CEL) was prepared incorporating a network of polymer nanofibres into the ion exchange matrix. The anion exchange layer (AEL) was prepared by automated spray coating. This approach had the twofold advantage of improving the mechanical stability and tuning the thickness of the anion exchange layer with benefits towards the overall resistance of the bipolar membrane. Electrospinning was the key process to prepare the interface region with three-dimensional (3D) architecture composed of anion exchange fibres and cation exchange fibres. A water dissociation catalyst was added at the 3D-junction to obtain a bipolar membrane suitable for electrolysis and CO2/H2O co-electrolysis applications. The CEL, AEL and the 3D-junction were characterised and the preparation of bipolar membranes with different interface regions was realised. The ionic resistance of bipolar membranes with layers of different thickness was measured. The contribution of each layer to the total resistance of the membrane was evaluated, parameter of significant relevance when designing a bipolar membrane. A study conducted on the electrochemical characterisation of the bipolar membranes clarified the importance of the ion exchange pre-treatment. The three-dimension bipolar interface is a valid architecture to incorporate water dissociation catalysts