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Retrovirus endogeni umani, vaccinazione per la febbre gialla e rischio di cancro
No full textIntroduction
Previous studies have shown that vaccination with BCG and/or smallpox and/or certain serious infections reduced the risk of melanoma. A search in a "genome database" revealed that all these infectious agents express epitopes with homology in the amino acid sequence with a peptide (named HERV-K-MEL), encoded by the human endogenous retrovirus K (HERV-K) and frequently expressed in melanoma. It was suggested that these homologues epitopes are able to generate a population of CD8+ T cells that stimulate a cross-reactive immune surveillance for melanoma and possibly some other types of cancer.
The yellow fever vaccine (YFV) also expresses an epitope with an amino acid sequence closely homologous to HERV-K-MEL. Therefore an epidemiological study was previously conducted to determine if this vaccine confers protection against melanoma. In a cohort of 28,306 vaccinated a reduced risk of melanoma was observed if YFV was administered at an early stage, preceding the clinical presentation of melanoma by 10 years or more.
HERV-K-MEL is a splicing variant of the envelope protein (HERV-K-Env). This protein and the splice variants can act as tumor-associated antigens. Immuno- histochemical methods have shown that the HERV-K Env proteins are expressed in human breast carcinomas. In these patients it was also demonstrated the presence of cellular (cytotoxic T lymphocyte, CTL activity with specific anti- HERV-K) and humoral (IgG anti-HERV-K) immune responses.
Finally, it was recently demonstrated that a monoclonal antibody against HERV- K-Env inhibited the growth of breast cancer cells in vitro, and reduced the tumor mass in mice treated with xenografts of human breast cancer, as compared to controls.
In view of the above, the present study aims to find out whether YFV reduced the likelihood of developing breast cancer and melanoma, and to verify the temporal pattern after vaccination with YFV 17D.
Methods
The study was conducted in the Veneto region (Northeastern Italy), where most of the region is covered by the Veneto Cancer Registry (VTR).
The Ethics Committee of the University of Padua and the Italian National Authority for the Protection of Sensitive Data authorized the study.
Under Italian law, YFV can be given only in authorized healthcare services and the personal data of vaccinated subjects must be recorded. All these services have agreed to cooperate. Migrants, minors, residents of Local Health Units (ASL) not covered by VTR and subjects vaccinated post cancer diagnosis were ruled out.
A record linkage between the vaccinees cohort and the VTR was carried out. Only the first tumor was considered in the statistical analysis, and further tumors occurring later were excluded. The mass of person-years was calculated by taking data entry as the date of vaccination (if after the coverage VTR) or the date of the start of VTR coverage (if subsequent to the date of vaccination). The end of follow up was set at 31 December 2005 (31 December 1999 for ASL 16 of Padua), or the date of cancer incidence, death or loss to follow-up, whichever was the first event.
The analysis was performed by Poisson regression. Using as comparison group the lowest category the ratio of incidence rates (IRR) and 95% confidence interval (CI) for the following covariates was estimated: calendar period (1987- 1991, 1992-1996, 1997-2001, 2002-2005), age (classes: 18-29, 30-59, 60 + years), and time elapsed since vaccination (TSV) in order to assess the time-effect relationship between cancer and YFV (classes : 0-1.9, 2-3.9, 4-5.9, 6-7.9, 8-9.9, 10-14.9, 15-plus years of TSV).
To distinguish the effect of the gene on the relationship between HERV-K, YFV and the risk of cancer, a case-control study was also performed, comparing separately cases of breast cancer and melanoma (mostly expressing HERV-K) with a control group consisting of patients diagnosed with all other tumors (mostly not expressing HERV-K). The odds ratio (OR) for breast cancer (or for melanoma, separately) and the 95% confidence interval (CI) were estimated by logistic regression analysis, where the dependent variable was 1 for cases and 0 for controls, and the independent variables were sex, age (classes: 18-29, 30-59, 60 + years), and TSV (classes: 0-1.9, 2-3.9, 4-5.9; 6-7.9, 8-9.9, 10-14.9, 15 + years after vaccination).
Results
The risk of breast cancer expressed as IRR per classes of TSV was reduced within the first 10 years after vaccination, reaching a minimum value of 0.64 in the class 4-5.9 years of TSV, for then gradually increasing to reach the unity in the class of 8-9.9 years of TSV. In the classes 10-14.9 and 15+ years of TSV the IRR was still close to 1.00. No IRR reached statistical significance.
In the case-control study the breast cancer risk was reduced in the classes 2-3.9 (OR = 0:33, p = 0.004) and 4-5.9 years (OR = 0:33, p = 0.004) of TSV, and then increased to reach a maximum value of 0.54 at 8-10 years after the vaccination. In the classes 10-14.9 and 15 or more years of TSV the OR was always less than 1.00. Concerning breast cancer, the OR values were systematically lower than the values of IRR in each class of TSV.
The IRR for melanoma risk reached the minimum value in the class 15 or more years since the vaccination (IRR = 0:50, p = 0.407). In the case-control study the ORs for melanoma reached the lowest value in the class 15 and more years after vaccination (OR = 0:30, p = 0.137). Even for melanoma the values of OR were systematically lower than the values of IRR in each class of TSV.
Comment of data
Consistently with the findings of previous studies on the relationship between other types of vaccination and risk of melanoma, we expected a similar pattern of protection for both tumors, i.e., a reduction in cancer risk 10 years after vaccination. It is indeed biologically plausible that the protective effect should be noticeable only when YFV is administered at an early stage of carcinogenesis, preceding the clinical presentation of cancer by many years. Breast cancer risk both in the case-control study and the cohort study showed instead a "U" trend for the risk of cancer, with maximum protection at 2-6 years of TSV (as for most, if not all, vaccines). The results of the case-control study instead confirmed that YFV conferred a degree of protection against melanoma if the vaccine was administered at least 10 years before the malignant transformation.
For both melanoma and breast cancer the case-control study expressed the protective effect induced by YFV in a more pronounced fashion than the cohort study. Therefore, the ORs were systematically lower than the IRRs. This fact confirmed that the protective effect of YFV may be due to the immune response induced by YFV cross-reacting with the HERV-K protein. Assuming an immune effect, there could be two coexisting responses (humoral and cellular) cross- reacting against HERV-K and YFV antigens. A humoral immune mechanism (IgG anti-HERV-K) seems to be involved in the protection against breast cancer because the response is relatively rapid and tends to wane in the long run. Regarding melanoma, in which protection is observed 10 or more years after the vaccination, the response is more likely to be cellular (CTL specific activity with anti-HERV-K).
The only statistically significant risk estimates were the ORs. Therefore, the results of this study should be interpreted with caution since they derive from the analysis of a case-control study: i.e. they can be rather used to explain the mechanism of protection from cancer rather than its degree in the general population.
It seems appropriate to confirm these results and conduct new studies in other cohorts with possibly longer TSV. It also seems appropriate to eliminate or at least mitigate the effect of potential confounding factors such as other vaccinations (BCG, smallpox and other vaccines recommended for tropical travels) and especially the socio-economic level, which is a recognized risk factor for various cancers including melanoma and breast cancer.
If the negative association between YFV and tumors expressing HERV-K-MEL was confirmed, new strategies for cancer prevention could be opened. Although monoclonal antibodies against HERV-K Env have recently shown interesting perspectives in the therapy of breast cancer, tumor immuno-therapy is still considered more complicated and less advantageous than immuno-prevention.Introduzione.
Precedenti studi hanno dimostrato che la vaccinazione con BCG e/o vaccino antivaiolo e/o alcune infezioni gravi riducevano il rischio di melanoma. Una ricerca in un “genome database” ha rivelato che tutti questi agenti infettivi esprimono epitopi con omologia di sequenza amminoacidica con un peptide (denominato HERV-K-MEL), codificato da retrovirus endogeni umani della serie K (HERV-K) e frequentemente espresso nel melanoma. È stato ipotizzato che questi epitopi omologhi siano in grado di generare una popolazione di linfociti T CD8 + cross-reattivi che stimolano una sorveglianza immunitaria verso il melanoma e possibilmente altri tipi di cancro.
Anche il vaccino contro la febbre gialla (YFV) esprime un epitopo con una sequenza aminoacidica strettamente omologa all’antigene HERV-K-MEL. Pertanto è stato condotto uno studio epidemiologico per determinare se questo vaccino conferiva una protezione contro il melanoma. In un precedente studio su una coorte di 28.306 vaccinati è stata evidenziata una riduzione del rischio di melanoma se YFV era somministrato in una fase precoce della cancerogenesi, che precedeva la presentazione clinica del melanoma di 10 anni o più.
HERV-K-MEL è una variante di splicing della proteina dell'involucro (HERV-K- Env). Questa proteina e le varianti di splicing possono agire come antigeni associati al tumore. Metodi immuno-istochimici hanno dimostrato che le proteine HERV-K Env sono espresse in carcinomi mammari umani. In queste pazienti è
stata anche dimostrata la presenza di risposte immunitarie cellulari (cytotoxic T lymphocyte, CTL, con attività specifica anti-HERV-K) e umorali (IgG anti-HERV-K).
Infine, è stato recentemente dimostrato che un anticorpo monoclonale contro HERV-K-Env inibiva la crescita delle cellule del cancro della mammella in vitro, e, nei topi con xenotrapianto di tumore mammario umano, riduceva la massa tumorale in quelli trattati rispetto ai topi di controllo.
In considerazione di quanto sopra, il presente studio si propone di indagare se YFV riduce la probabilità di sviluppare il cancro al seno e melanoma, e di verificare l'andamento temporale dell’associazione dopo vaccinazione con YFV 17D.
Metodi.
Lo studio è stato condotto in Veneto, regione del Nord-Est Italia, dove gran parte della regione è coperta dal Registro Tumori del Veneto (VTR).
Il Comitato Etico dell'Università degli Studi di Padova e l'Autorità Nazionale Italiana per la Protezione dei Dati Sensibili hanno autorizzato lo studio.
Secondo la legge italiana, YFV può essere somministrato solo nei servizi sanitari autorizzati e i dati personali dei soggetti vaccinati devono essere registrati. Tutti questi servizi hanno accettato di collaborare. Sono stati esclusi dalla coorte i migranti, i minori di 18 anni, i residenti in Aziende Sanitarie Locali (ASL) non coperte da VTR, e i soggetti vaccinati dopo la data di diagnosi di cancro.
Il follow-up della coorte è stato condotto mediante record-linkage con i dati del VTR. Nell'analisi statistica è stato considerato solo il primo tumore, escludendo altri tumori verificatisi in seguito. La massa di persone-anni è stata calcolata prendendo come data entry la data di vaccinazione (se successiva alla copertura VTR) o la data di avvio della copertura VTR (se successiva alla data della vaccinazione). La data di uscita del follow up è il 31 dicembre 2005 (31 dicembre 1999 per l’ ASL 16 di Padova), oppure la data di incidenza del cancro, morte o perdita al follow-up, a seconda di quale fosse stato il primo evento.
L'analisi è stata eseguita mediante la regressione di Poisson. Usando come gruppo di confronto la categoria più bassa è stato stimato il rapporto dei tassi di incidenza (IRR) e l’intervallo di confidenza al 95% (IC) per le seguenti covariate: periodo di calendario (1987-1991, 1992-1996, 1997-2001, 2002-2005), età (classi: 18-29, 30-59, 60 e più anni), e tempo trascorso dalla vaccinazione (TSV) al fine di valutare la relazione tempo-effetto tra YFV e cancro (classi: 0-1.9; 2-3.9; 4-5.9; 6-7.9; 8-9.9; 10-14.9; 15 e più anni di TSV).
Per distinguere l'effetto del gene HERV-K sulla relazione tra YFV e il rischio di cancro è stato anche eseguito uno studio caso-controllo, contrastando i casi di cancro al seno e, separatamente, i casi di melanoma (che per lo più esprimono HERV-K) con un gruppo di controllo composto da pazienti affetti da tutti gli altri tumori (che per lo più non esprimono HERV-K). L'Odds Ratio (OR) per il tumore al seno (o per il melanoma, separatamente) e l’intervallo di confidenza al 95% (IC) sono stati stimati con l’analisi della regressione logistica, in cui la variabile dipendente era 1 per i casi e 0 per i controlli, e le variabili indipendenti erano sesso, età (classi: 18-29, 30-59, 60 + anni), e TSV (classi: 0-1.9; 2-3.9; 4-5.9; 6- 7.9; 8-9.9; 10-14.9; 15+ anni dalla vaccinazione).
Risultati.
Il rischio di cancro mammario espresso come IRR nelle classi di TSV si riduceva entro i primi 10 anni dalla vaccinazione, raggiungendo un valore minimo di 0.64 nella classe 4-5.9 anni di TSV, e quindi gradualmente aumentava sino a raggiungere l’unità nella classe 8-9.9 anni di TSV. Nelle classi 10-14.9 e 15 e più anni di TSV l’IRR oscillava restando vicino a 1.00. Nessun IRR raggiungeva la significatività statistica.
Allo studio caso-controllo il rischio di cancro mammario si riduceva nelle classi TSV di 2-3.9 (OR=0.33; p=0.004) e 4-5.9 anni (OR=0.33; p=0.004), quindi aumentava sino a raggiungere un valore massimo di 0.54 dopo 8-10 anni dalla vaccinazione. Nelle classi 10-14.9 e 15 e più anni di TSV, l’OR era sempre inferiore a 1.00. Per quanto riguarda il tumore della mammella, i valori di OR erano sistematicamente più bassi dei valori di IRR in ogni classe di TSV.
L’ IRR per il rischio di melanoma raggiungeva il valore minimo nella classe 15 e più anni dalla vaccinazione (IRR=0.50; p=0.407). Allo studio caso controllo gli OR per melanoma raggiungevano il valore più basso nella classe 15 e più anni dalla vaccinazione (OR=0.30; p=0.137). Anche per il melanoma i valori di OR erano più bassi dei valori di IRR in ogni classe di TSV.
Commento dei dati.
Coerentemente con le conclusioni di precedenti valutazioni sulla relazione tra altri tipi di vaccinazione e rischio di melanoma, ci si aspettava un modello di protezione simile per entrambi i tumori, cioè una riduzione del rischio 10 anni dopo la vaccinazione. È infatti biologicamente plausibile che l'effetto protettivo debba essere evidente solo quando YFV è somministrato in una fase precoce della carcinogenesi che precede di molti anni la presentazione clinica del tumore. Invece, per il tumore mammario sia lo studio caso-controllo e sia lo studio coorte hanno evidenziato un andamento a “U” del rischio di cancro, con protezione massima a 2-6 anni di TSV (come per la maggior parte, se non tutti, i vaccini). Invece, i risultati dello studio caso-controllo hanno confermato che YFV conferiva un certo grado di protezione verso il melanoma se il vaccino veniva somministrato almeno 10 anni prima della trasformazione maligna.
Sia per il melanoma sia per il tumore mammario, lo studio caso-controllo esprimeva l’effetto protettivo indotto da YFV in maniera più accentuata che lo studio coorte. Pertanto gli OR erano sistematicamente inferiori agli IRR. Questo fatto confermava che l’effetto protettivo di YFV può essere dovuto alla risposta immunitaria indotta da YFV che cross-reagisce con la proteina HERV-K. Se la protezione è un effetto immunitario, ci potrebbero essere due risposte (una risposta umorale ed una risposta cellulare) coesistenti che cross-reagiscono contro gli antigeni HERV-K e YFV. Un meccanismo immunitario umorale (IgG anti- HERV-K) sembra coinvolto nella protezione contro il cancro mammario poiché la risposta è relativamente rapida e tende ad esaurirsi nel lungo periodo. Invece, per quanto riguarda il melanoma, in cui la protezione si osserva dopo più di 10 anni dalla vaccinazione, è più probabile che la risposta sia di tipo cellulare (CTL con attività specifica anti-HERV-K).
Le stime di rischio statisticamente significative riguardavano solo gli OR. Pertanto i risultati del presente studio vanno interpretati con cautela giacché derivano dall’analisi di uno studio caso-controllo: possono cioè essere utilizzati più che altro per spiegare il meccanismo della protezione dal cancro piuttosto che il grado della stessa nella popolazione generale.
Sembra opportuno confermare questi risultati e replicare lo studio in altre coorti con TSV possibilmente più lunghi. Sembra inoltre opportuno eliminare o almeno attenuare l’effetto di potenziali fattori confondenti come altre vaccinazioni (BCG, vaiolo e altri vaccini raccomandati per viaggi tropicali) e sopratutto il livello socio-economico, che è un fattore rischio riconosciuto per vari tumori fra cui il melanoma e il cancro della mammella.
Se l’associazione negativa tra YFV e tumori esprimenti HERV-K-MEL fosse confermata potrebbero aprirsi nuove possibili strategie per la prevenzione del cancro. Nonostante anti-corpi monoclonali contro antigeni HERV-K Env hanno recentemente dimostrato interessanti prospettive nella terapia del tumore del seno, l’immuno-terapia rimane ancora più complicata e meno vantaggiosa rispetto all’immuno-prevenzione
PREVALENCE AND RISK FACTORS OF LONG-COVID-19 SYNDROME IN HEALTH CARE WORKERS: A MULTI-CENTRE STUDY FROM NORTH-EASTERN ITALY, ORCHESTRA PROJECT WORKING GROUP
No full textPREVALENCE AND RISK FACTORS OF LONG-COVID-19 SYNDROME IN HEALTH CARE WORKERS: A MULTI-CENTRE STUDY FROM NORTH-EASTERN ITALY, ORCHESTRA PROJECT WORKING GROUP / Cegolon, Luca; Sansone, Donatella; Tassinari, Alice; Murgia, Nicola; Monaco, Maria Grazia Lourdes; Spiteri, Gianluca; Modenese, Alberto; Gobba, Fabrizio Maria; Pavanello, Sofia; Liviero, Filippo; Scapellato, Maria Luisa; Porru, Stefano; Filon, Francesca Larese. - In: OCCUPATIONAL MEDICINE. - ISSN 0962-7480. - 74:Supplement_1(2024), pp. 0-0. (Intervento presentato al convegno 34th International Congress on Occupational Health ICOH 2024 tenutosi a Marrakesh (Morocco) nel 28th April-3rd May 2024) [10.1093/occmed/kqae023.0452]
Sensitization to Nickel (Sulphate 5%) in North-Eastern Italy, 1997-2023: Prevalence, Trend Over Time and an Evaluation of the Occupational Risk
No full textBackground: Prevalence of nickel sensitization is heterogeneous worldwide, and in Europe, it is higher in Southern compared to Northern European countries, a likely reflection of delayed and less stringent application of the EU directive 94/27/CE. This multicentre study aimed at investigating prevalence and factors associated with positive patch test reactions to nickel in North-eastern Italy during 1997-2023.
Methods: A cross-sectional study design was employed to estimate the yearly prevalence of positive patch test reactions to nickel sulphate 5% among 31 948 consecutive outpatients patch tested with the Triveneto series for suspected allergic contact dermatitis during 1997-2023 in four centres of Triveneto (North-Eastern Italy). Reading was performed at 48 h and 72 h/96 h. Multiple logistic regression separated by sex of patients was employed to investigate factors (birth year, atopic dermatitis, occupational dermatitis, body area affected and occupation) potentially associated with nickel sensitization, expressing the results as adjusted odds ratio (aOR) with 95% confidence intervals (95% CI).
Results: Prevalence of nickel sensitization was 26.05% during 1997-2004 and 26.40% across 1997-2023 (excluding Trento-Bolzano-Rovigo), reducing over time in all centers combined. Prevalence of positive reactions significantly increased over the years during 1997-2004 among males yet reduced across the entire study period (1997-2023) among females Results (Logistic regression analysis). Regardless of the study period, nickel sensitization was significantly lower in males and followed an inverse U-shape with respect to birth year among females, increasing from 35.70% in those born during 1955-1964 to 46.24% in females born during 1965-1974, reducing to 41.36% in those born during 1975-1984. With regard to occupation, a significantly higher prevalence of positive patch test reactions to nickel was observed among sellers, whereas it was lower in retirees and housewives.
Conclusions: Although decreasing over time, the prevalence of positive patch test reactions in this study is confirmed to be higher than that in Northern European countries. The latter pattern probably reflects delayed and less stringent application of the European directive. The U-trend of positive patch test reactions by birth year in female patients points to nickel exposure and sensitization in females aged 20-50 years before the enforcement of the European directive. Higher prevalence of positive patch test reactions in sellers could reflect prolonged exposure in coin handling occupations, whereas lower prevalence in retirees and housewives may be a result of reduced immune reactivity with increasing age
COVID-19 in City Council Civil Servants, 1 March 2020–31 January 2023: Risk of Infection, Reinfection, Vaccine Effectiveness and the Impact of Heterologous Triple Vaccination
No full textThe risk of COVID-19 increases in any occupation entailing intense social interactions. This study aimed to investigate the impact of COVID-19 among civil servants of Trieste city council (northeastern Italy) over the entire pandemic. Methods. The crude incidence rate of COVID-19 was estimated from 1 March 2020 to 31 January 2023 by explanatory factors, expressing the estimate as COVID-19 events x 10,000 person-days (P-d) at risk. A multivariable Cox proportional hazard regression model was fitted to examine the risk of primary COVID-19 infection and reinfections, reporting adjusted hazard ratios (aHR) with 95% confidence interval (95% CI). Results: The cohort of Trieste city council was mainly composed of administrative clerks (48.5%), nursery teachers (33%), technicians (9.9%) and local police officers (8.5%). Between 1 March 2020 and 31 January 2023, 1444 (62.4%) employees tested positive for SARS-CoV-2 at least once and 18.1% (=262/1444) at least twice. By the end of this study, 55% (N = 1272) of employees had received at least three doses of COVID-19 vaccine, whereas 19.7% (N = 457) remained unvaccinated. At multiple Cox regression analysis, the adjusted risk of primary COVID-19 events during the entire study period increased in employees aged 40–49 years (aHR = 1.65; 95% CI: 1.01; 2.71), females (aHR = 1.28; 95%CI: 1.12; 1.45), local police officers (aHR = 1.82; 95%CI: 1.50; 2.22) and nursery teachers (aHR = 1.27; 95%CI: 1.13; 1.43). However, whilst the risk of primary infections in police officers increased already during the Alpha transmission period (aHR = 6.82; 95%CI: 4.48; 10.40), progressively reducing across subsequent variants, for nursery teachers, it increased during the Delta wave (aHR = 2.42; 1.70; 3.44), reducing with Omicron (aHR = 1.23; 95%CI: 1.07; 1.40). Compared to unvaccinated colleagues, during the entire study period the risk of primary infections was significantly lower in employees immunized with three (aHR = 0.42; 95%CI: 0.36; 0.47) or four (aHR = 0.30; 95%CI: 0.23; 0.40) doses of COVID-19 vaccine, for a vaccine effectiveness (VE) of 58% and 70%, respectively. The protective effect of vaccination against primary infections was confirmed in the sub-group analysis by main pandemic waves, for a VE of 75% for one dose against 99% for two doses during the Alpha transmission period, slightly reducing to 59% and 70% in Delta time, respectively. During the Omicron wave, the risk of primary SARS-CoV-2 infections diminished significantly with three (aHR = 0.42; 95%CI: 0.36; 0.49) or four vaccine doses (aHR = 0.09; 95%CI: 0.05; 0.16), for a VE of 58% and 91%, respectively. Moreover, the risk of primary SARS-CoV-2 reinfections during the entire study period reduced with one (aHR = 0.47; 95%CI: 0.27; 0.82), two (aHR = 0.42; 95%CI: 0.30; 0.58), three (aHR = 0.32; 95%CI: 0.24; 0.44) or four vaccine doses (aHR = 0.14; 95%CI: 0.05; 0.46), for a VE of 53%, 58%, 68% and 86% against reinfections, respectively. No significant difference in VE was associated with heterologous versus homologous triple vaccination, both against primary infections or reinfections. Conclusions. Primary SARS-CoV-2 infections were more likely among nursery teachers and local police officers. The risk of both primary infections and reinfections reduced with higher number of doses of COVID-19 vaccine, regardless of the pandemic wave. Since city council civil servants were swab tested on demand or for contact tracing, the estimation of COVID-19 risk and VE largely missed aymptomatic SARS-CoV-2 infections. On the one hand, the present study confirmed the protective effect of COVID-19 vaccination against symptomatic SARS-CoV-2 infections; on the other hand, it highlighted not only the importance of continuous booster doses to keep up the humoral immunity over time but also the importance of updated vaccine formulations to prevent and control the spread of a highly mutable virus. Moreover, the protective effect of the first two doses against reinfections confirmed the efficacy of hybrid immunity during Omicron time
A Multi-Center Study on Sensitization to Thimerosal in North-Eastern Italy, 1997–2023: Prevalence, Risk Factors, the Role of Occupation and the Impact of Vaccinations
No full textBackground: Thimerosal has been widely used as a preservative to prevent microbial growth in medications and vaccines. However, in 1999 its removal from vaccine formulations was called for due to concerns about its potential side effects on humans, with subsequent reduced sensitizations at patch tests. The present multi-center study investigated the epidemiological, occupational and temporal pattern of sensitization to Thimerosal in North-Eastern Italy during 1997–2023 and associated factors. Methods: Due to variability in patch testing and positive reactions by the centers, this study was broken down by three periods: 1997–2004 (including all centers but Trieste); 1997–2015 (considering only Padua and Pordenone); and 2010–2023 (considering only Trieste and Pordenone). Multiple logistic regression was used to investigate prevalence of sensitization to Thimerosal and associated factors. Results were expressed as adjusted odds ratio (aOR) with 95% confidence intervals (95%CI). Results: Prevalence of positive patch test reactions to Thimerosal decreased from (8.13%) in 1997 to 0.95% in 2023 across all centers combined. Prevalence of positivity to Thimerosal was 9.49% during 1997–2004 (in all centers yet excluding Trieste), 8.41% during 1997–2015 (considering only Padua and Pordenone) and 4.01% during 2010–2023 (considering only Trieste and Pordenone). A significantly decreasing trend of Thimerosal sensitization was observed during 1997–2015 (aOR = 0.94; 95%CI: 0.92; 0.95). Regardless of the study period, sensitization to Thimerosal was consistently and significantly higher among health care workers (HCWs) and in patients born during 1981–1990. Conclusions: The significantly decreasing prevalence of sensitization to Thimerosal over time likely reflected removal policies from vaccines and medications after 1999. Likewise, the higher prevalence of patch test reactions in patients born during 1981–1990 may mirror the widespread presence of this hapten in vaccines and medications in the 1980ies. Moreover, the increased prevalence of patch test reactions positive to Thimerosal in HCWs probably reflected higher influenza vaccination uptake in this group compared to other occupational categories. Positive patch test reactions to Thimerosal after 2000 were likely clinically irrelevant though
Seawater Pools Versus Freshwater Pools to Treat Inflammatory Skin Diseases and Rheumatic Conditions: A Scoping Review
No full textSeawater is a long-standing remedy against a number of skin or rheumatic conditions since ancient times, now popular in many countries, where spa, thalassotherapy and seawater pools have considerably boomed. Exposure to seawater and sunlight is an essential component of thalassotherapy, defined by any controlled interaction with marine environments and their natural elements, even in the absence of skin applications of algae, sands or muds. Seawater pools therefore offer the opportunity of thalassotherapy to patients unable to go the beach or during the winter months. The evidence from various studies seems to converge on combined exposure to solar radiation and seawater as a more effective approach than irradiation alone or bathing in freshwater followed by irradiation to reduce symptoms of inflammatory skin diseases or rheumatic conditions. An unwanted consequence of chlorine-based treatment of seawater is the formation of disinfection-by-products (DBPs) due to reactions of disinfectants with organic matter of anthropogenic origin released by bathers. Whilst chlorination of freshwater predominantly generates chlorinated DBPs, the prevailing species produced by chlorination of seawater pools are brominated DBPs, reportedly more genotoxic. However, despite greater toxicity of brominated DBPs, there is evidence that DBPs concentration in freshwater pools is significantly higher (probably due to the larger number of users) compared to seawater pools. Containing the number of bathers could therefore reduce the risk of exposure to DBPs in both types of pool. The outdoor location of pools can further contribute to reducing the risk of genotoxicity thanks to volatilization, airborne dispersion and photodegradation of some DBPs
Epidemiological and Occupational Pattern of Patch-Test Reactions to p-Tert-butylphenol-formaldehyde Resin in North-Eastern Italy, 1997–2021
No full textBackground. Skin contact with items containing p-tert-butylphenol-formaldehyde resin (PTBP-FR) may induce sensitization and allergic contact dermatitis (ACD). Methods. This multi-centric cross-sectional study investigated the prevalence of sensitization to PTBP-FR in 30,629 consecutive outpatients patch-tested during 1997–2021 in four research centers from Northern Italy: Padua; Pordenone; Trieste; and Trento/Bolzano/Rovigo. Patch tests were applied on the upper back of patients with suspected ACD. All patches were removed after 48 h and read at 72 or 96 h. Results. The overall prevalence of PTBP-FR sensitization was 1.11% (=341/30,629) of cases, with lower prevalence occurring in the Province of Trento/Bolzano/Rovigo (0.36%). The body area most frequently affected were the hands (36.32%), followed by face (19.52%) and legs (8.09%). During 1997–2004, the prevalence of PTBP-FR positivity was significantly lower in Trento/Bolzano/Rovigo (aOR = 0.19; 95%CI: 0.11; 0.35), whereas it was higher among restaurant workers (aOR = 2.44; 95%CI: 1.44; 4.13). During the entire study period (1997–2021), excluding Trento/Bolzano/Rovigo, PTBP-FR positivity significantly decreased in the period 2011–2021 (aOR = 052; 95%CI: 0.39; 0.69) compared to 1997–2010 in males (OR = 0.69; 95%CI: 0.52; 0.91). Conclusions. Females were likely to react to PTBP-FR at patch tests. Prevalence of PTBP-FR sensitization significantly decreased over time, possibly reflecting reduced occupational and non-occupational exposure due to replacement of the resin with other adhesive products (acrylates or epoxy agents)
Artificial intelligence as a tool for enhancing the performance of public health emergency operation centres (EOC)
No full textEmergency Operation Center (EOC) is a designated physical space centralizing the coordination of emergency response activities. Modern EOCs extend their utility to preparedness activities and functions as early warning platforms, monitoring potential emergency indicators in a “watch” mode.
We considered the potential application of Artifical Intelligence (AI) into the operationalization of EOC. Specifically, AI stands as a transformative force in the operational effectiveness of a PHEOC throughout the public health emergency management cycle, which covers the preparedness, response, and recovery phases. In the preparedness phase, AI delves into historical data, employing predictive analytics to foresee potential emergency scenarios and disease outbreaks, thereby strengthening the PHEOC’s state of readiness.
AI supports decision-makers by integrating diverse information streams, enhancing situational awareness, and suggesting evidence-based actions for prompt response. The integration of AI into PHEOC operations represents a paradigm shift in public health emergency management. Through intelligent data processing and predictive analytics
Lung cancer risk in subjects exposed to organic dust: an unexpected and surprising story
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