The “polonium in vivo” study. Polonium-210 in bronchial lavages of patients with suspected lung cancer

Few studies have reported on polonium-210, a decay breakdown product of radon-222 and lead-210, in human lungs and there has been no study in patients with suspected lung cancer. The main aim of this "Polonium in vivo" study was to evaluate polonium-210 radioactivity in bronchopulmonary systems of smoker, ex-smoker and never smoker patients with suspected lung cancer. Alpha-spectrometric analyses were performed on bronchial lavage (BL) fluids from two Italian hospitals in 2013-2016. Socio-demographic, smoking, occupational and spirometric characteristics, lung cancer confirmation and histologic type and radon-222 concentration in patients' homes were collected. Seventy BL samples from never (n = 13), former (n = 35) and current smokers (n = 22) were analyzed; polonium-210 was detected in all samples from current and former smokers and in 54% of samples from never smokers (p < 0.001; median values: 1.20, 1.43 and 0.40 mBq, respectively). Polonium-210 levels were significantly higher in COPD versus no COPD patients (median value: 3.60 vs. 0.97 mBq; p = 0.007); former and current smokers, without and with COPD, had significantly increased polonium-210 levels (p = 0.012); 96% of confirmed versus 69% of non-confirmed lung cancer patients recorded detectable polonium-210 levels (p = 0.018). A polonium-210 detectable activity was measured in BL samples from all current and former smokers. Polonium-210 in the lungs could be the result of lead-210 entrapment, which, with its half-life of 22 years, could provide a continuous emission of alpha radioactivity, even many years after quitting, thus proposing a possible explanation for the onset of lung cancer, particularly in former smokers

Increased Risk of Metabolic Syndrome in Antidepressants Users: A Mini Review

Mounting evidence has shown that the risk of metabolic syndrome (MetS) is substantially overlapping in the diagnostic subgroups of psychiatric disorders. While it is widely acknowledged that patients receiving antipsychotic medications are at higher risk of MetS than antipsychotic-naive ones, the association between antidepressants and MetS is still debated. The goal of our mini review was to analyse the relationship among depressive symptoms, antidepressant use and the occurrence of MetS. Adhering to PRISMA guidelines, we searched MEDLINE, reference lists and journals, using the following search string: (((“Mental Disorders”[Mesh]) AND “Metabolic Syndrome”[Mesh]) AND “Antidepressive Agents”[Mesh]), and retrieved 36 records. Two reviewers independently assessed records and the mini review eventually included the data extracted from 8 studies. The Newcastle-Ottawa Scale was used to assess the quality of the selected studies. Overall, the results of the mini review seem to support the association among depressive symptoms, antidepressants therapy and MetS. Except for H1-R high-affinity ones, the relationship between antidepressants and MetS still needs to be clarified. Considering the widespread prescription of antidepressants, both on behalf of psychiatrists and primary care physicians, further research on this topic is recommended

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database

: Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083)

State of the art of 18F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation

Aim The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([F-18]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [F-18]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections. Methods In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [F-18]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [F-18]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020. Results Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication. Conclusions Currently, [F-18]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a "common nuclear physicians' language" throughout all the country

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Colore ed identità nel recupero dei centri storici

Il paesaggio dei centri storici, nelle parole di Eugenio Turri, costituisce il “risultato ultimo, visivo, di portata ambientale, ecologica, dei percorsi storici, sociali e psicologici. Esso è la proiezione del nostro Heimat, dell’ambiente del nostro vivere, riferimento delle nostre più profonde identità”. Una vera azione integrata di recupero e tutela di un paesaggio costruito o naturale deve diventare “un fatto intimo, da riportare alla coscienza individuale, anche se rientra tra i grandi fatti territoriali, collettivi e addirittura planetari”; un fortissimo senso di rispetto verso un dono “troppo spesso tradito in cambio di beni puramente materiali”. Il centro storico è il luogo della complessità, non solo dal punto di vista della forma urbana ma anche del sistema di funzioni e relazioni che si manifestano e si radicano proprio all'interno del suo tessuto. Al fine di superare alcuni nodi sostanziali, come la mancanza di un’adeguata cultura progettuale che evidenzi come il colore e la sua tutela siano tra i fattori che descrivono l’identità di un tessuto urbano, si propongono metodologie di conoscenza della città storica e azioni integrate di recupero e di progetto del colore. Attualmente non vi sono procedure codificate e/o capitolati per il rilevamento urbano dei centri storici che siano finalizzati alla conservazione attiva del costruito e che integrino, con codici prescrittivi e repertori tipologici, i regolamenti urbanistici. La conoscenza di un tessuto storico, opportunamente descritto per caratteristiche morfologiche, tipologiche e strutturali, è necessaria per indirizzare il recupero dell’identità

Strumenti e modelli per la rappresentazione dello spazio urbano

The codified representation and measurement of the traditional city, of historical centres, of their urban shape and typological components (architecture and technology of the façades, materials, and colours) is devised to encourage a process innovation and to facilitate the restoration and maintenance of the urban heritage. The historical centre of European cities is, by its own nature, a complex place whose image and urban culture must be preserved by the use of appropriate guidelines. The “Colour Plan, An Architecture, Material, and Colour Design Code for the Historical Centre” is an urbanistic tool whose prescriptions act as fixed guidelines for all the interventions carried out in the area covered by the Plan itself, i.e. the historical centre. The codes will be integrated with other architectural design tools and uploaded into a GIS system.La necessità di misurare e documentare lo spazio urbano e l’introduzione delle strumentazioni digitali forniscono l’occasione di ampliare le tecniche per il rilevamento e la rappresentazione dei centri storici. Le innovazioni riguardano tanto il metodo di approccio alle problematiche relative all’intervento sull’esistente che la gestione dei dati conoscitivi e dello stesso progetto d’intervento, rendendo tra loro comunicanti i diversi livelli di conoscenza, dalla scala architettonica del singolo manufatto a quella più urbana. Il “Piano del Colore, Architettura, Materiali e Colori per il centro storico”, qui presentato, costituisce uno strumento urbanistico esecutivo e di dettaglio, le cui disposizioni hanno valore prescrittivo e sono strutturate al fine di una successiva integrazione con gli strumenti progettuali o informativi