A New Approach for a Safe and Reproducible Seeds Positioning for Diffusing Alpha-Emitters Radiation Therapy of Squamous Cell Skin Cancer: A Feasibility Study

The purpose of this study is to discuss how to use an external radio-opaque template in the Diffusing Alpha-emitters Radiation Therapy (DaRT) technique’s pre-planning and treatment stages. This device would help to determine the proper number of sources for tumour coverage, accounting for subcutaneous invasion and augmenting DaRT safety. The procedure will be carried out in a first phase on a phantom and then applied to a clinical case. A typical DaRT procedure workflow comprises steps like tumour measurements and delineation, source number assessment, and therapy administration. As a first step, an adhesive fiberglass mesh (spaced by 2 mm) tape was applied on the skin of the patient and employed as frame of reference. A physician contoured the lesion and marked the entrance points for the needles with a radio opaque ink marker. According to the radio opaque marks and metabolic uptake the clinical target volume was defined, and with a commercial brachytherapy treatment planning system (TPS) it was possible to simulate and adjust the spatial seeds distribution. After the implant procedure a CT was again performed to check the agreement between simulations and seeds positions. With the procedure described above it was possible to simulate a DaRT procedure on a phantom in order to train physicians and subsequently apply the novel approach on patients, outlining the major issues involved in the technique. The present work innovates and supports DaRT technique for the treatment of cutaneous cancers, improving its efficacy and safety

Diffusing alpha particles radiation treatment optimization in clinical settings

Alpha-particle emitters, notably used in 224Ra-DaRT, have emerged as effective in overcoming radiation resistance and providing targeted cancer therapy. These emitters cause DNA double-strand breaks, visualizable in human lymphocytes. The 224Ra DaRT technique, using a decay chain from seeds, extends alpha particle range, achieving complete tumor destruction while sparing healthy tissue. This thesis examines a biokinetic model, validated with patient data, and a feasibility study on skin squamous cell carcinomas are discussed. The study reports 75% tumor complete response rate and 48% patients experiencing acute grade 2 toxicity, resolving within a month. An observed abscopal effect (AE), where tumor regression occurs at non-irradiated sites, is examined, highlighting DaRT's potential in triggering anti-tumor immune responses. This effect, coupled with DaRT's high-linear energy transfer (LET), suggests its superiority over low-LET radiation in certain clinical scenarios. Improvements to DaRT, including the use of an external radio-opaque template for treatment planning, are explored. This advancement aids in determining source numbers for optimal tumor coverage, enhancing DaRT’s safety. The thesis outlines a typical DaRT procedure, from tumor measurements to source assessment and administration, emphasizing the importance of precise seed positioning. Furthermore, the thesis discusses DaRT's potential in treating prostate cancer, a prevalent global health issue, by offering an alternative to traditional salvage therapies. DaRT seeds, delivering alpha particle-based interstitial radiation, require precision in seed insertion due to their limited tissue range. In conclusion, the thesis advocates for DaRT's role in treating solid tumors, emphasizing its improved radiobiological potency and potential benefits over beta and gamma source-based therapies. Ongoing studies are assessing DaRT's feasibility in treating various solid tumors, including pancreatic, breast, prostate, and vulvar malignancies, suggesting a promising future in cancer treatment

Toward an Energy-Autonomous Wearable System for Human Breath Detection

This work presents a research about a 5.8 GHz system for vital signals monitoring, specifically human breath. The system consists of two main components: a Self-Injection Locked Oscillator (SILO), whose input and output ports are aperture-coupled to a dual-polarized patch antenna, and a passive receiver, coupled to the SILO output port, consisting of the cascade connection of a peak detector and a full-wave RF-to-DC rectifier. The SILO generates the carrier, that is frequency-modulated by chest displacements and backscattered to the SILO itself. The latter is loosely coupled to the passive receiving sub-system. In this way, the SILO output signal is simultaneously demodulated by the detector, and DC-converted to provide energy for the wireless communication of the received vital signals, e.g. by means of an IoT (Internet of Things) low-power node. The system is designed for being fully wearable; it can be mounted inside a plastic case and worn by the user under test at chest-level position. Critical breath rates can be detected and sent to a caregiver, thus enabling monitoring of chronic diseases, such as bradypnea or tachypnea, while performing a normal life

A glass of red wine to keep vascular disease at bay, but what about pemphigus vulgaris?

Pemphigus vulgaris is a rare autoimmune blistering disease, involving the skin and mucous epithelia, which is characterized by flaccid blisters and erosions. It is caused by the presence of autoantibodies directed against desmoglein, a glycoprotein that plays a critical role in cell-cell attachment. Upon a predisposing genetic background, different agents have been shown to act as triggers for the pathogenesis of pemphigus. The most evident association is with drug intake, while the role of diet is often underestimated. The aim of this article is to review the possible role of tannins, a group of phenolic metabolites that are widely distributed in almost all plant foods and beverages, particularly red wine, as a trigger for pemphigus vulgaris

Beyond the skin: disease parameters in pemphigus

Pemphigus represents a group of rare autoimmune bullous diseases that affect the skin and mucous membranes. This group has a chronic course leading to high morbidity and mortality. Because of the painful chronic-recurring blisters and/or erosions on skin and mucosa, pemphigus can impair quality of life (QOL). Therapeutic modalities, anxiety and depression can also have an additional negative impact in the QOL of the pemphigus patients. Since the nature and course of the pathology and the fact that pemphigus worsens the quality of life of affected patients, scoring systems to objectively evaluate the clinical activity of the disease and to correlate that with the QOL are needed. Nowadays the most used global scales to assess the clinical activity of pemphigus are the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), the Pemphigus Disease Area Index (PDAI) and the Pemphigus Visual Activity Scale (PVAS). To evaluate the patient's generic QOL the most used score is the Dermatology Life Quality Index (DLQI), but all the sponsered clinical trials in pemphigus are using ABQOL this rather than DLQI

Efficiency and calibration factors for continuous monitoring systems of airborne radioactivity in ducts: Monte Carlo, analytical and experimental approaches compared

In this work a set of calibration constants to measure the 18F airborne activity in straight ducts with square section are computed by means of a Geant4 simulation and provided for different duct lengths. The calibration constants are compared with analytical calculations and experimental measurements. The simulated calibration constants provide a useful cross-check for the actual calibration of airborne monitoring systems in ducts, which is practically complex and can be affected by large uncertainties

Herpes simplex virus infection in pemphigus vulgaris: clinical and immunological considerations

Different environmental factors have been implicated in the pathogenesis of pemphigus vulgaris (PV), including drugs, diet, burns, X-rays, ultraviolet radiation, neoplasms, and infections. Several reports described the manifestation or aggravation of PV due to herpes simplex virus (HSV), varicella-zoster virus, Epstein-Barr virus, cytomegalovirus and human herpesvirus-8 infections. In the present study, we correlated secondary HSV1 infection in 3 PV patients on immunosuppressive treatment with the titers of IgG autoantibodies against desmoglein 1 (DSG1) and 3 (DSG3) over a follow-up period of at least 18 months. In these patients, the detection of HSV1 and clinical flare-up of PV did not correlate with a significant increase of DSG-specific IgG. Thus, secondary cutaneous HSV infections should be considered in patients with chronic PV with atypical sudden relapses or resistance to sufficient immunosuppressive treatment who do not show an increase of DSG-specific IgG autoantibodies

CARBON DIOXIDE ANGIOGRAPHY: SIMULATION OF OPERATIVE CONDITIONS FOR DIAGNOSTIC IMAGE OPTIMIZATION

Carbon dioxide angiography is based on the visualization (i.e., the radiographic contrast) of gas bubbles injected in blood vessels. By using an experimental X-ray bench, the energy response of a flat panel detector has been measured (Varian CB4030) and, with a dedicated phantom and a software simulation, the image contrast of vessels is injected with Iodine and CO2. Moreover, the dynamical behavior of a moving gas bubble has been studied with the software simulator. The results show that the contrast generated by carbon dioxide is about one fourth of that obtained with iodine, demonstrating that CO2 angiography should use different radiological settings with respect to iodine angiography. In particular, a kVp increase has a lower reduction of contrast-to-noise-ratio (CNR) with carbon dioxide than with iodinated contrast medium (CM), suggesting possible technological improvements both on radiological emission and image enhancement methods

Infliximab monotherapy in neuro-Beh\ue7et's disease: four year follow-up in a long-standing case resistant to conventional therapies

Beh\ue7et's disease (BD) is a vasculitis characterized by hallmark lesions of oral and genital ulcers (Krause andWeinberger, 2008). Involvement of parenchymal central nervous system (neuro-BD) is a serious complication commonly characterized by brainstem and/or basal ganglia lesions (Al- Araji and Kidd, 2009). To date, the treatment of neuro-BD remains largely empirical, andmay not adequately control the disease (Al-Araji and Kidd, 2009). Given the well-recognized role played by tumor necrosis factor-\u3b1 (TNF\u3b1) in the pathogenesis of active BD (Santos Lacomba et al., 2001), infliximab (a monoclonal antibody that binds to and neutralizes the activity of TNF\u3b1) has been adopted with favorable results in patients resistant to conventional immunosuppressive therapies and in a small placebo controlled study (Goossens et al., 2001; Arida et al., 2010)