Outbreaks of autochthonous Dengue in Lazio region, Italy, August to September 2023: preliminary investigation.

Between August and September 2023, three distinct autochthonous dengue virus transmission events occurred in Lazio, Italy, with the main event in Rome. The events involved three different dengue serotypes. No link with previous imported cases was identified. Here we describe the epidemiological and phylogenetic analysis of the first autochthonous cases and the implemented control actions. The multiple transmission events call for a strengthening of the vector control strategies and future research to better characterise the risk in countries like Italy.

3D-printed graphene polylactic acid devices resistant to SARS-CoV-2: Sunlight-mediated sterilization of additive manufactured objects.

Additive manufacturing has played a crucial role in the COVID-19 global emergency allowing for rapid production of medical devices, indispensable tools for hospitals, or personal protection equipment. However, medical devices, especially in nosocomial environments, represent high touch surfaces prone to viral infection and currently used filaments for 3D printing can't inhibit transmission of virus [1]. Graphene-family materials are capable of reinforcing mechanical, optical and thermal properties of 3D printed constructs. In particular, graphene can adsorb near-infrared light with high efficiency. Here we demonstrate that the addition of graphene nanoplatelets to PLA filaments (PLA-G) allows the creation of 3D-printed devices that can be sterilized by near-infrared light exposure at power density analog to sunlight. This method has been used to kill SARS-CoV-2 viral particles on the surface of 3D printed PLA-G by 3 min of exposure. 3D-printed PLA-G is highly biocompatible and can represent the ideal material for the production of sterilizable personal protective equipment and daily life objects intended for multiple users.

INSIDIA 2.0 High-Throughput Analysis of 3D Cancer Models: Multiparametric Quantification of Graphene Quantum Dots Photothermal Therapy for Glioblastoma and Pancreatic Cancer.

Cancer spheroids are in vitro 3D models that became crucial in nanomaterials science thanks to the possibility of performing high throughput screening of nanoparticles and combined nanoparticle-drug therapies on in vitro models. However, most of the current spheroid analysis methods involve manual steps. This is a time-consuming process and is extremely liable to the variability of individual operators. For this reason, rapid, user-friendly, ready-to-use, high-throughput image analysis software is necessary. In this work, we report the INSIDIA 2.0 macro, which offers researchers high-throughput and high content quantitative analysis of in vitro 3D cancer cell spheroids and allows advanced parametrization of the expanding and invading cancer cellular mass. INSIDIA has been implemented to provide in-depth morphologic analysis and has been used for the analysis of the effect of graphene quantum dots photothermal therapy on glioblastoma (U87) and pancreatic cancer (PANC-1) spheroids. Thanks to INSIDIA 2.0 analysis, two types of effects have been observed: In U87 spheroids, death is accompanied by a decrease in area of the entire spheroid, with a decrease in entropy due to the generation of a high uniform density spheroid core. On the other hand, PANC-1 spheroids' death caused by nanoparticle photothermal disruption is accompanied with an overall increase in area and entropy due to the progressive loss of integrity and increase in variability of spheroid texture. We have summarized these effects in a quantitative parameter of spheroid disruption demonstrating that INSIDIA 2.0 multiparametric analysis can be used to quantify cell death in a non-invasive, fast, and high-throughput fashion.

Legionella pneumonia: increased risk after COVID-19 lockdown? Italy, May to June 2020.

We report a case of Legionella pneumonia in a dishwasher of a restaurant in Rome, Italy, just after the end of the lockdown that was in place to control the SARS-CoV-2 epidemic. The case highlights the importance of strict monitoring of water and air systems immediately before reopening business or public sector buildings, and the need to consider Legionella infections among the differential diagnosis of respiratory infections after lockdown due to the ongoing COVID-19 pandemic.

[Spatial analysis for detecting clusters of cases during the COVID-19 emergency in Rome and in the Lazio Region (Central Italy)]. / Analisi spaziale per l'identificazione di cluster di casi durante l'emergenza COVID-19 a Roma e nel Lazio.

BACKGROUND: one of the most affected European countries by the COVID-19 epidemic is Italy; data show the strong geographical heterogeneity of the epidemic. OBJECTIVES: to propose an analysis strategy to ascertain the non-random nature of the spatial spread of COVID-19 cases infection and identify any territorial aggregations, in order to enhance contact tracing activities in specific areas of the Lazio Region (Central Italy) and a large urban area as Rome. METHODS: all cases of COVID-19 of the Lazio Region notified to the Regional Service for Epidemiology, Surveillance, and Control of Infectious Diseases (Seresmi) with daily updates from the beginning of the epidemic to April 27, 2020 were considered. The analyses were carried out considering two periods (the first from the beginning of the epidemic to April 6 and the second from the beginning of the epidemic to April 27) and two different levels of spatial aggregation: the entire Lazio region excluding the Municipality of Rome, where the 377 municipalities represent the area units, and the Municipality of Rome, where the area units under study are the 155 urban areas (ZUR). The Scan statistic of Kulldorff was used to ascertain the non-random nature of the spatial spread of infected cases and to identify any territorial aggregations of cases of COVID-19 infection, using a retrospective spatial analysis in two overlapping periods. RESULTS: analysis was conducted at regional level in the two survey periods and revealed the presence of 7 localized clusters. In the Municipality of Rome, a single cluster (Historic Centre) was identified in the first period which includes 7 urban areas, while in the second period two distinct clusters (Omo and Farnesina) were observed. CONCLUSIONS: Scan statistics are an important surveillance tool for monitoring disease outbreaks during the active phase of the epidemic and a useful contribution to epidemiological surveillance during the COVID-19 epidemic in a specific territory.

Killing Two Birds with One Stone: Is the COVID-19 Vaccination Campaign an Opportunity to Improve Adherence to Cancer Screening Programmes? The Challenge of a Pilot Project in a Large Local Health Authority in Rome.

The COVID-19 pandemic has affected health services worldwide. The suspension of cancer screening programs during the lockdown period, coupled with the other measures taken to limit the SARS-CoV-2 spread, contributed to the idea that cancer preventive interventions are deferrable. In this opinion paper, we present some data on cancer screening coverage in one of the largest Local Health Authorities in Italy in recent years. Within this context, we introduce the benefits of a pilot project in which we took advantage of the great attention on the COVID-19 vaccination campaign to improve screening uptake. In this project, we offered men and women eligible for cancer screening the opportunity to book appointments while waiting to be vaccinated. In addition, trained healthcare personnel were available on-site to discuss any barriers to participation with the attendees. Despite the project having only just started, preliminary results are encouraging, with positive feedback from the attendees. In conclusion, we advocate for the need to adopt a comprehensive approach when it comes to population health, and we use this project as an example to discuss how it is possible to contribute to minimizing the long-term impact of the COVID-19 pandemic with resources already in place.

Multilayer intensity modulated contact interventional radiotherapy (brachytherapy): Stretching the therapeutic window in skin cancer.

Interventional radiotherapy (IRT, brachytherapy) is a highly effective treatment method for non-melanoma skin cancer (NMSC). Traditionally, the maximum depth of NMSC lesions considered eligible for contact IRT was 5 mm; however, following several national surveys and recent recommendations, such cut-off, lesions thicker than 5 mm may be treated by contact IRT. The use of image guidance in defining the actual depth in treating NMSC to correctly identify clinical target volume (CTV) and prevent unnecessary toxicity is of paramount importance. The aim of the paper was to describe a multilayer arrangement of catheters to treat NMSC lesions thicker than 5 mm, thus proposing an example of dynamic intensity modulated IRT, using different catheter-to-skin distance of sources to reach the best CTV coverage and maximally reduce the excess of dose to the skin.

The "Lazio ADVICE" telemedicine platform: First results of general practitioners' usage, facilitators and barriers in the Local Health Authority Roma 1.

Background: Telemedical approaches represent a valuable tool for the management of coronavirus disease 2019 patients, allowing daily clinical assessment, monitoring of vital parameters, remote visits, and prescription of treatment or hospitalization in case of clinical worsening. This cross-sectional study aims to evaluate the use, barriers and facilitators of the "Lazio ADVICE" telemedical platform, a regional system for remote assistance for coronavirus disease 2019 patients at home, according to General Practitioners and Family Pediatricians of the Local Health Authority Roma 1, during the coronavirus disease 2019 pandemic. Methods: An interview-based survey was performed between December 2020 and January 2021. The survey investigated the demographic information of General Practitioner and Family Pediatricians, the knowledge of the platform, frequency of utilization, usefulness, strengths and weaknesses, and hypothesis of future implementation proposed. Results: We interviewed 214 physicians and 89 (41.6%) were classified as users and 125 (58.4%) as non-users. Older age and working in District 1, 14 and 15 (vs. District 13) significantly reduced the probability of using the platform physician. Among the 89 users, 19 (21.3%) used the platform every day or even several times a day, 40 (44.9%) several times a week but less than one access per day, 30 (33.7%) used the platform several times a month up to one entry per week. Most of them (92.3%) consider the platform useful. Barriers were poor integration with software and work routine (76.4%), and usability issues (53.9%). Among the 125 non-users, 14 (11.2%) didn't know the existence of the platform, 60 (48.0%) never tried it and 51 (40.8%) tried to use it. Reported reasons for the interruption of use were not very user-friendly (45.1%), perceived useless (37.3%), non-optimal functioning (23.5%), and lack of time (19.6%). Conclusion: The pandemic accelerated the implementation of telemedicine services around Lazio Region, starting a positive and continuous exchange of experiences, activities and best practices among physicians.

Interventional Radiotherapy (Brachytherapy) for Nasal Vestibule: Novel Strategies to Prevent Side Effects.

Interventional radiotherapy (brachytherapy) has become the new therapeutic standard in the management of early stages nasal vestibule tumors; in fact it allows for high local control rates and low toxicity profiles. However, since more and more patients will receive interventional radiotherapy (brachytherapy) as primary treatment, it is desirable to implement novel strategies to reduce the dose to organs at risk with the future aim to result in further lowering long-term side effects. MATERIALS AND METHODS: We were able to identify two different strategies to reduce dose to the treatment volume, including the implantation technique (the implant can be interstitial, endocavitary or mixed and the catheters may be placed either using the Paris system rules or the anatomical approach) and the dose distribution within the implant (the most commonly used parameter to consider is the dose non-uniformity ratio). We subsequently propose two novel strategies to reduce dose to organs at risk, including the use of metal shields for fixed organs as in the case of the eyes and the use of a mouth swab to push away mobile organs, such in the case of the mandible. We used two different algorithms to verify the values namely the TG-43 and the TG-186. RESULTS: We provided an accurate literature review regarding strategies to reduce toxicity to the treatment volume, underlining the pros and cons of all implantation techniques and about the use dose non-uniformity ratio. Regarding the innovative strategies to reduce the dose to organs at risk, we investigated the use of eye shielding and the use of swabs to push away the mandible by performing an innovative calculation using two different algorithms in a series of three consecutive patients. Our results show that the dose reduction, both in the case of the mandible and in the case of eye shielding, was statistically significant. CONCLUSION: Proper knowledge of the best implantation technique and dose non-uniformity ratio as highlighted by existing literature is mandatory in order to reduce toxicity within the treatment volume. With regard to the dose reduction to the organs at risk we have demonstrated that the use of eye shielding and mouth swab could play a pivotal role in clinical practice; in fact, they are effective at lowering the doses to the surrounding organs and do not require any change to the current clinical workflow.

Dosimetric impact of applying a model-based dose calculation algorithm for skin cancer brachytherapy (interventional radiotherapy).

Purpose: Brachytherapy (BT, interventional radiotherapy) is a well-established radiotherapy technique capable of delivering high doses to tumors while sparing organs at risk (OARs). Currently, the clinically accepted dose calculation algorithm used is TG-43. In the TG-186 report, new model-based dose calculation algorithms (MBDCA), such as Elekta's advanced collapsed cone engine (ACE), have been introduced, although their clinical application is yet to be fully realized. This study aimed to investigate two aspects of TG-186: firstly, a comparison of dose distributions calculated with TG-43 and TG-186 for skin tumors; and secondly, an exploration of the impact of using a water bolus on the coverage of clinical target volume (CTV) and OARs. Material and methods: Ten treatment plans for high-dose-rate IRT were developed. All plans were initially calculated using the TG-43 algorithm, and were subsequently re-calculated with TG-186. In addition, one of the treatment plans was assessed with both TG-43 and TG-186, using 10 different water bolus thicknesses ranging from 0 to 5 cm. To assess dose variations, the following dose-volume histogram (DVH) parameters were compared: D2cc and D0.01cc for OARs, and V150, V100, V95 and V90 for CTV coverage. Results and conclusions: The average dosimetric results for CTV and OARs, as calculated by both algorithms, revealed statistically significant lower values for TG-186 when compared with TG-43. The presence of a bolus was observed to enhance CTV coverage for the TG-186 algorithm, with a bolus thickness of 2 cm being the point at which ACE calculations matched those of TG-43. This study identified significant differences in dosimetric parameters for skin tumors when comparing the TG-43 and TG-186 algorithms. Moreover, it was demonstrated that the inclusion of a water bolus increased CTV coverage in TG-186 calculations.

Advanced usage of Ti3C2Tx MXenes for photothermal therapy on different 3D breast cancer models.

Globally, breast cancer is the most diagnosed invasive cancer among women. Current therapies (e.g., chemotherapy) show numerous limitations due to the lack of selectivity and involved side effects, which urgently asks for novel approaches with enhanced tumor-killing efficacy. We previously demonstrated that MXenes, new bioactive nanomaterials with promising photophysical properties, are capable to increase the efficiency of the targeted breast cancer photothermal therapy (PTT). In this work, we investigated the effect of few- and multi-layer Ti3C2Tx MXenes mediated-PTT on two different 3D reliable breast cancer models such as conventional and bio-printed spheroids. We performed PTT on both cancer models using a non-toxic MXene concentration of 50 µg/mL. After PTT, a significant reduction in the cell viability along with a notable increase in reactive oxygen species (ROS) was observed. Moreover, we studied the effect of PTT on the migration of macrophages and endothelial cells toward cancer regions in both 3D models. Our results indicate that PTT mediated by both few- and multi-layer MXenes significantly modulates the tumor progression through cells' death by increasing the temperature, which holds particularly true for the bio-printed model.

Coordinated innate and T-cell immune responses in mild COVID-19 patients from household contacts of COVID-19 cases during the first pandemic wave.

Objective: To better define the immunopathogenesis of COVID-19, the present study aims to characterize the early immune responses to SARS-CoV-2 infection in household contacts of COVID-19 cases. In particular, innate, T- and B-cell specific responses were evaluated over time. Methods: Household contacts of COVID-19 cases screened for SARS-CoV-2 infection by nasopharyngeal swab for surveillance purposes were enrolled (T0, n=42). Of these, 28 subjects returned for a follow-up test (T1). The innate response was assessed by detecting a panel of soluble factors by multiplex-technology in plasma samples. Cell-mediated response was evaluated by measuring interferon (IFN)-γ levels by ELISA in plasma harvested from whole-blood stimulated with SARS-CoV-2 peptide pools, including spike (S), nucleocapsid (N) and membrane (M) proteins. The serological response was assessed by quantifying anti-Receptor-Binding-Domain (RBD), anti-Nucleocapsid (N), whole virus indirect immunofluorescence, and neutralizing antibodies. Results: At T0, higher levels of plasmatic IFN-α, IL-1ra, MCP-1 and IP-10, and lower levels of IL-1ß, IL-9, MIP-1ß and RANTES were observed in subjects with positive swab compared to individuals with a negative one (p<0.05). Plasmatic IFN-α was the only cytokine detectable in subjects with positive SARS-CoV-2 swabs with high accuracy for swab score positivity (0.93, p<0.0001). Among subjects with positive swabs, significant negative correlations were found among the RT-PCR cycle threshold values reported for genes S and N and IFN-α or IP-10 levels. At T0, the IFN-γ T-cell specific response was detected in 50% (5/10) of subjects with positive swab, while anti-RBD/anti-N antibodies showed a positivity rate of 10% (1/10). At T1, the IFN-γ T-cell specific response was detected in most of the confirmed-infection subjects (77.8%, 7/9), whereas the serological response was still observed in a minority of them (44.4%, 4/9). Overall, the swab test showed a moderate concordance with the T-cell response (78.6%, k=0.467), and a scarce concordance with the serological one (72.9%, k=0.194). Conclusions: Plasmatic IFN-α and the IFN-γ T-cell specific response appear early even in the absence of seroconversion, and show a greater positivity rate than the serological response in household contacts with positive swab.

The management of the Sars-CoV-2 pandemic in Italy, lessons earnt and reflections for the future.

BACKGROUND: Italy and especially Lombardy region was the first European Country hit by the covid 19 pandemic, without a proper preparedness plan. Italy's health-care service is a regionally based National Health Service (NHS) that provides universal coverage, largely free of charge at the point of service. Aim of this paper is to analyse the national and especially the regional strategies put in place to face the pandemic, focusing on the impact of the overlap of the political and health competences among national and regional authority. METHODS: Italian hygiene and preventive medicine society (SITI) realized a questionnaire submitted to National Institute for Health and regional stakeholder to investigate the response to the epidemic analysing the strategies and actions put in place both by the national and regional governments and the regional health authorities. RESULTS: The national survey highlighted several critical points in the management of the covid 19 pandemic in the different regional contexts such as lack of personnel in preventive departments and preparadness. CONCLUSIONS: Lessons learnt during the pandemic should shape the future of the Italian health service. (www.actabiomedica.it).

Urban Health and Social Marginality: Perceived Health Status and Interaction with Healthcare Professionals of a Hard-to-Reach Community Living in a Suburban Area of Rome (Italy).

The study reports an urban health investigation conducted in Bastogi, an outskirt of Rome (Italy) characterised by social marginalization and deprivation. Our aim was to analyse the health perception, health-related behaviours, and interaction with healthcare professionals of the inhabitants of Bastogi compared to the population living in the area of the same local health unit (ASL). The Progresses of Health Authorities for Health in Italy questionnaire (PASSI) was administered to a sample of 210 inhabitants of Bastogi. Data were analysed and compared to those of the ASL collected in 2017-2018. The socio-economic indicators showed an overall worse condition for the inhabitants of Bastogi, with a significantly higher proportion of foreign and unemployed residents and a lower educational level compared to the ASL. Significant differences in the prevalence of non-communicable diseases, mental health complaints, and participation in prevention strategies, including cancer screening, were found. The questionnaire showed a lower help-seeking behaviour and a lack of reliance on health professionals in Bastogi inhabitants. Our findings highlight how social determinants produce health inequities and barriers to accessing healthcare. The difficulties of conducting quantitative research in complex and hard-to-reach contexts, characterized by high social vulnerability, are outlined.

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives.

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.

Italian Public Health Response to the COVID-19 Pandemic: Case Report from the Field, Insights and Challenges for the Department of Prevention.

: The coronavirus disease (COVID-19) outbreak is rapidly progressing globally, and Italy, as one of the main pandemic hotspots, may provide some hard lessons for other countries. In this paper, we summarize the current organizational capacity and provide a pragmatic and narrative account of strategies and activities implemented by the Department of Prevention (Dipartimento di Prevenzione)-the regional entity of the Local Health Authority of the Italian National Health Service in charge of public health-since the beginning of the outbreak. We conduct a preliminary analysis of general strengths, weaknesses, opportunities, and threats (SWOT) of the response strategies from a local perspective. Furthermore, we provide firsthand insights on future directions and priorities to manage this unprecedented pandemic. Our case report gives a qualitative view of the healthcare response, based on the experience of frontline professionals, with the aim to generate hypotheses about factors which may promote or hinder the prevention and management of a pandemic locally. We highlight the importance of a public health approach for responding to COVID-19 and reshaping healthcare systems.

Impact of diverticular inflammation and complication assessment classification on the burden of medical therapies in preventing diverticular disease complications in Italy.

BACKGROUND: Several treatments are currently advised to manage diverticular disease (DD) patients, but their impact on the burden of the disease is unknown. Our aim was to assess the economic analysis of using the recent Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification on the burden of medical therapies prescribed in preventing DD complications occurrence in Italy. METHODS: We assessed retrospectively the cost/year of treatments in estimated DICA 1, DICA 2 and DICA 3 population. Analysis of diverticulosis prevalence was estimated according to data population provided by Italian Institute of Statistics (ISTAT). Cost of treatments calculated according to data on drugs' consumption collected during the DICA study. RESULTS: We estimated that >8 million of Italian people >60 years may have diverticulosis, and that about 75% of diverticular population are on DICA 1, about 30% on DICA 2, and about 13% on DICA 3. We estimated that >387 million of euros could be spent in DICA 1 population, >203 million of euros in DICA 2 population, and >88 million of euros in DICA 3 population. Since medical treatments did not show any significant advantage when treating DICA 1 and DICA 3 people in terms of prevention of acute diverticulitis occurrence/recurrence and surgery occurrence, we can estimated that >475 million of euros could be spent in Italy without any significant benefit in preventing DD complications occurrence. CONCLUSIONS: DICA endoscopic classification may have a significant impact on the burden of DD in Italy, because it helps to select DD people who effectively need treatments in terms of prevention of acute diverticulitis occurrence/recurrence and surgery occurrence.