Residential exposure to air pollution and incidence of leukaemia in the industrial area of Viadana, Northern Italy.

BACKGROUND: Exposure to air pollution has been proposed as one of the potential risk factors for leukaemia. Work-related formaldehyde exposure is suspected to cause leukaemia. METHODS: We conducted a nested register-based case-control study on leukaemia incidence in the Viadana district, an industrial area for particleboard production in Northern Italy. We recruited 115 cases and 496 controls, frequency-matched by age, between 1999 and 2014. We assigned estimated exposures to particulate matter (PM10, PM2.5), nitrogen dioxide (NO2), and formaldehyde at residential addresses, averaged over the susceptibility window 3rd to 10th year prior to the index date. We considered potential confounding by sex, age, nationality, socio-economic status, occupational exposures to benzene and formaldehyde, and prior cancer diagnoses. RESULTS: There was no association of exposures to PM10, PM2.5, and NO2 with leukaemia incidence. However, an indication of increased risk emerged for formaldehyde, despite wide statistical uncertainty (OR 1.46, 95%CI 0.65-3.25 per IQR-difference of 1.2 µg/m3). Estimated associations for formaldehyde were higher for acute (OR 2.07, 95%CI 0.70-6.12) and myeloid subtypes (OR 1.79, 95%CI 0.64-5.01), and in the 4-km buffer around the industrial facilities (OR 2.78, 95%CI 0.48-16.13), although they remained uncertain. CONCLUSIONS: This was the first study investigating the link between ambient formaldehyde exposure and leukaemia incidence in the general population. The evidence presented suggests an association, although it remains inconclusive, and a potential significance of emissions related to industrial activities in the district. Further research is warranted in larger populations incorporating data on other potential risk factors.

Two-dimensional perfusion angiography permits direct visualization of redistribution of flow in hepatocellular carcinoma during b-TACE.

OBJECTIVES: To demonstrate in vivo redistribution of the blood flow towards HCC's lesions by utilizing two-dimensional perfusion angiography in b-TACE procedures. MATERIAL AND METHODS: In total, 30 patients with 35 HCC nodules treated in the period between January 2019 and November 2021. For each patient, a post-processing software leading to a two-dimensional perfusion angiography was applied on each angiography performed via balloon microcatheter, before and after inflation. On the colour map obtained, reflecting the evolution of contrast intensity change over time, five regions of interests (ROIs) were assessed: one on the tumour (ROI-t), two in the immediate peritumoural healthy liver parenchyma (ROI-ihl) and two in the peripheral healthy liver parenchyma (ROI-phl). The results have been interpreted with a novel in silico model that simulates the hemodynamics of the hepatic arterial system. RESULTS: Among the ROIs drawn inside the same segment of target lesion, the time-to-peak of the ROI-t and of the ROI-ihl have a significantly higher mean value when the balloon was inflated compared with the ROIs obtained with deflated balloon (10.33 ± 3.66 s vs 8.87 ± 2.60 s (p = 0.015) for ROI-t; 10.50 ± 3.65 s vs 9.23 ± 2.70 s (p = 0.047) for ROI-ihl). The in silico model prediction time-to-peak delays when balloon was inflated, match with those observed in vivo. The numerical flow analysis shows how time-to-peak delays are caused by the obstruction of the balloon-occluded artery and the opening of intra-hepatic collateral. CONCLUSION: The measurements identify predictively the flow redistribution in the hepatic arteries during b-TACE, supporting a proper positioning of the balloon microcatheter.

Chest CT features of COVID-19 in vaccinated versus unvaccinated patients: use of CT severity score and outcome analysis.

OBJECTIVES: To evaluate the impact of vaccination on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moreover on coronavirus disease 2019 (COVID-19) pneumonia, by assessing the extent of lung disease using the CT severity score (CTSS). METHODS: Between September 2021 and February 2022, SARS-CoV-2 positive patients who underwent chest CT were retrospectively enrolled. Anamnestic and clinical data, including vaccination status, were obtained. All CT scans were evaluated by two readers using the CTSS, based on a 25-point scale. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between CTSS and clinical or demographic variables. An outcome analysis was used to differentiate clinical outcome between vaccinated and unvaccinated patients. RESULTS: Of the 1040 patients (537 males, 503 females; median age 58 years), 678 (65.2%) were vaccinated and 362 (34.8%) unvaccinated. Vaccinated patients showed significantly lower CTSS compared to unvaccinated patients (p < 0.001), also when patients without lung involvement (CTSS = 0) were excluded (p < 0.001). Older age, male gender and lower number of doses administered were associated with higher CTSS, however, in the multivariate analysis, vaccination status resulted to be the variable with the strongest association with CTSS. Clinical outcomes were significantly worse in unvaccinated patients, including higher number of ICU admissions and higher mortality rates. CONCLUSIONS: Lung involvement during COVID-19 was significantly less severe in vaccinated patients compared with unvaccinated patients, who also showed worse clinical outcomes. Vaccination status was the strongest variable associated to the severity of COVID-related, more than age, gender, and number of doses administered.

[Global evaluation of the mortality and hospitalization in the Italian contaminated sites included in the SENTIERI project]. / Stime globali della mortalità e ospedalizzazione nei siti contaminati italiani inclusi nel progetto SENTIERI.

Since 2006, epidemiological surveillance of populations living in Italian contaminated sites has been ongoing (SENTIERI Project). Updated global estimates of mortality (2013-2017) and hospitalization (2014-2018) are reported. The excess deaths (observed-expected) for the main groups of diseases were calculated for all the 46 sites together. Through a random-effect meta-analysis of the standardized mortality and hospitalization rates (SMR/SHR), the pooled SMR/SHR for all the sites and their groupings were estimated. In the 46 sites, 8,342 exceeding deaths (1,668/year) were estimated, 4,353 in males and 3,989 in females, resulting in an excess risk of 2% in both genders. The risk of hospitalization for all causes was in excess of 3%. These excesses are mainly attributable to malignant tumours. In subgroups of sites, exceeding SMRs were observed for all mesotheliomas and pleural mesotheliomas, lung and colorectal cancers in both genders. SHR for all causes were observed in excess in the first year of life (+8%), in the group 0-19 and 20-29 years (+3-5%); no excesses of mortality were observed in the group 0-29 years.

[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report]. / SENTIERI - Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Sesto Rapporto.

INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest. METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources. RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males:pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered. LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources. CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.

Enantioselective Rhodium-Catalyzed Pauson-Khand Reactions of 1,6-Chloroenynes with 1,1-Disubstituted Olefins.

An enantioselective rhodium(I)-catalyzed Pauson-Khand reaction (PKR) using 1,6-chloroenynes that contain challenging 1,1-disubstituted olefins is described. In contrast to the previous studies with these types of substrates, which are only suitable for a single type of tether and alkyne substituent, the new approach results in a more expansive substrate scope, including carbon and heteroatom tethers with polar and non-polar substituents on the alkene. DFT calculations provide critical insight into the role of the halide, which pre-polarizes the alkyne to lower the barrier for metallacycle formation and provides the proper steric profile to promote a favorable enantiodetermining interaction between substrate and chiral diphosphine ligand. Hence, the chloroalkyne enables the efficient and enantioselective PKR with 1,6-enynes that contain challenging 1,1-disubstituted olefins, thereby representing a new paradigm for enantioselective reactions involving 1,6-enynes.

Asymmetric Azidation under Hydrogen Bonding Phase-Transfer Catalysis: A Combined Experimental and Computational Study.

Asymmetric catalytic azidation has increased in importance to access enantioenriched nitrogen containing molecules, but methods that employ inexpensive sodium azide remain scarce. This encouraged us to undertake a detailed study on the application of hydrogen bonding phase-transfer catalysis (HB-PTC) to enantioselective azidation with sodium azide. So far, this phase-transfer manifold has been applied exclusively to insoluble metal alkali fluorides for carbon-fluorine bond formation. Herein, we disclose the asymmetric ring opening of meso aziridinium electrophiles derived from ß-chloroamines with sodium azide in the presence of a chiral bisurea catalyst. The structure of novel hydrogen bonded azide complexes was analyzed computationally, in the solid state by X-ray diffraction, and in solution phase by 1H and 14N/15N NMR spectroscopy. With N-isopropylated BINAM-derived bisurea, end-on binding of azide in a tripodal fashion to all three NH bonds is energetically favorable, an arrangement reminiscent of the corresponding dynamically more rigid trifurcated hydrogen-bonded fluoride complex. Computational analysis informs that the most stable transition state leading to the major enantiomer displays attack from the hydrogen-bonded end of the azide anion. All three H-bonds are retained in the transition state; however, as seen in asymmetric HB-PTC fluorination, the H-bond between the nucleophile and the monodentate urea lengthens most noticeably along the reaction coordinate. Kinetic studies corroborate with the turnover rate limiting event resulting in a chiral ion pair containing an aziridinium cation and a catalyst-bound azide anion, along with catalyst inhibition incurred by accumulation of NaCl. This study demonstrates that HB-PTC can serve as an activation mode for inorganic salts other than metal alkali fluorides for applications in asymmetric synthesis.

Impact of infectious comorbidity and overall time of hospitalization in total outpatient management of acute myeloid leukemia patients following venetoclax and hypomethylating agents.

Venetoclax (VEN) and hypomethylating agent (HMAs) regimens are emerging as the standard of care for unfit for chemotherapy acute myeloid leukemia (AML) patients, but the safety and feasibility of a total outpatient management have not been fully investigated. Fifty-nine AML patients with active disease received VEN and HMAs. Nineteen out of 59 (32.2%) patients received the first cycle as inpatients, whereas 40/59 (67.8%) patients were treated in the outpatient setting. No significant differences were observed with regard to incidence of adverse events (AEs), including tumor lysis syndrome (TLS), and the 30-day and 60-day mortality was comparable. Notably, an infectious prophylaxis inspired to that adopted during intensive chemotherapy resulted in a low infection rate with a reduced bacterial infections incidence in out- versus hospitalized patients (p < .0001). The overall time of hospitalization was significantly shorter in patients who received a total outpatient treatment as compared to those who received the first cycle as inpatients (5.9 vs. 39.7 days, p < .0001). Despite the adopted differences in treatment management, the efficacy was similar. These data indicate that a total outpatient management of VEN and HMAs is feasible in AML patients without negatively impacting on treatment efficacy and may yield pharmacoeconomic and quality-of-life benefits.

Convalescent plasma for haematological patients with SARS-CoV-2 pneumonia and severe depletion of B-cell lymphocytes following anti-CD20 therapy: a single-centre experience and review of the literature.

Convalescent plasma (CP) therapy might be effective in patients with haematological malignanciesand B-cell depletion. We report a single-centre experience of COVID-19 patients with non-Hodgkinlymphoma and absence of B-cells as a consequence of anti-CD20 therapy successfully treated withCP from October 2020 to May 2021. CP was given in the presence of pneumonia with respiratoryfailure despite standard treatment and consisted of three infusions on an alternate-day basis. A reviewof the current literature on this topic was also performed. Six patients were identified (medianage 59.5 years (range 50-73)). The last anti-CD20 drug administration occurred 60 days before infection(range 0-360). CP was administered after a median of 51 days (range 9-120) from SARS-CoV-2diagnosis, with an early improvement in all but one subject. We suggest a possible clinical benefitof convalescent CP treatment in COVID-19 patients with haematological malignancies and B-celldepletion having persistent/recurrent pneumonia.

Role of CT and MR imaging in the assessment of suspected spondylodiscitis and planning of needle biopsy.

PURPOSE: Our aim was to assess the role of computed tomography (CT) or magnetic resonance imaging (MRI) in the assessment of spondylodiscitis, identifying the best target structures for biopsy to increase the likelihood of positive cultures. MATERIALS AND METHODS: This study was approved by our Institutional Review Board, and requirement for specific consent form was waived. In this retrospective single Institution study, we evaluated clinical and imaging records of 60 patients who underwent spine biopsy for suspected spondylodiscitis from January 2016 to May 2021. CT and MRI sensitivity and inter-reader agreement were assessed according to the phase of spondylodiscitis, defined as acute, subacute or chronic. Inter-reader agreement for the diagnosis and identification of spondylodiscitis phase was assessed using K statistics. Univariate logistic regression analysis was performed to assess any relationship between MRI/CT findings, spondylodiscitis phase and positive cultures. RESULTS: Sixty patients (48 males) with mean age 59, 2 ± 29 were enrolled in this study. MRI showed higher sensitivity (96% vs 65% of CT) in the diagnosis and good inter-reader agreement (k = 0.8) in the identification of the acute and subacute phase of spondylodiscitis, and moderate inter-reader agreement (k = 0.7) and lower sensitivity (80% vs 95% of CT) for the chronic phase. Univariate analysis showed as MRI-specific findings such as extensive hyperintensity of vertebral body and/or disc on Short Tau Inversion Recovery-T2w images, paravertebral collections, preserved or augmented disc height and presence of a vertebral fractures were mainly found in the acute/subacute phase and was a predictor for positive cultures (p < 0.05). CONCLUSION: MRI and CT are both able to identify the different phases of spondylodiscitis, although MRI is more sensitive in the acute phase. Findings such as extensive hyperintensity of the disc/vertebral body, fractures and paravertebral collections, represent the main targets for biopsy related to a positive culture.

Association of serum Krebs von den Lungen-6 and chest CT as potential prognostic factors in severe acute respiratory syndrome SARS-CoV-2: a preliminary experience.

PURPOSE: To correlate in COVID-19 pneumonia CT-based semi-quantitative score of pulmonary involvement with high serum levels of KL-6, a biomarker of disease severity. METHODS: Between March 28 to May 21, 2020, 196 patients with strong suspicion of SARS-CoV-2 were evaluated with RT-PCR for SARS-CoV-2, chest CT scan and blood test, including KL-6 serum protein, in our Emergency Unit. The final population included only patients who underwent blood sampling for KL-6 within 5 days from CT scan (n = 63), including n = 37 COVID-19-positive patients and n = 26 with negative RT-PCR testing for SARS-CoV-2 (control group). A semi-quantitative CT score was calculated based on the extent of lobar involvement (0:0%; 1, < 5%; 2:5-25%; 3:26-50%; 4:51-75%; 5, > 75%; range 0-5; global score 0-25). RESULTS: CT score was significantly correlated with serum value of KL-6 (r = 27, p = 0.035). This correlation was also present in COVID-19 positive patients (r = 0.423, p = 0.009) and CT score median value was significantly higher in patients with high KL-6 value (> 400 U/mL; 12.00, IQR 5.00-18.00, p-value 0.027). In control group, no statistically significant correlation was found between CT score and KL-6 value and CT score was higher in patients with high KL-6, although this difference was not statistically significant (5.00, IQR:1.75-8.00 versus 3.50, IQR:2.00-6.50). "Crazy paving" at the right upper (n = 8; 61.5%) and middle lobe (n = 4; 30.8%) and "consolidation" at the middle lobe (n=5; 38.5%) were observed in COVID-19 group with a significant difference between patients with high KL-6 value. CONCLUSION: CT score is highly correlated with KL-6 value in COVID-19 patients and might be beneficial to speed-up diagnostic workflow in symptomatic cases.

Chest computed tomography score, cycle threshold values and secondary infection in predicting COVID-19 mortality.

This retrospective and observational cohort study investigated chest computed tomography (CT) findings, cycle threshold (Ct) values in RT-PCR of SARS-CoV-2 and secondary infection occurrence to predict prognosis in COVID-19 patients. At hospital admission, CT findings and Ct values were collected. Microbiology tests performed after 48 hours from hospitalization were reviewed. According to in-hospital mortality, patients were grouped into non-survivors and survivors. Among 283 patients evaluated, in-hospital mortality rate was 13.8% (39/283). Secondary infection occurrence was 15.2% (43/283). Cut-off values for CT score >13.5 (AUC=0.682 p=0.0009) and for Ct <23.4 (AUC=0.749, p<0.0001) were predictive of death. Super-additive and synergic effects between high CT score plus secondary infection occurrence as well as between high CT score plus low Ct values affecting patient's outcome were observed. Chest CT score and Ct values in RT-PCR of SARS-CoV-2 could have a combination role for severity stratification of COVID-19 patients.

Quantitative CT texture analysis in predicting PD-L1 expression in locally advanced or metastatic NSCLC patients.

PURPOSE: The assessment of Programmed death-ligand 1 (PD-L1) expression has become a game changer in the treatment of patients with advanced non-small cell lung cancer (NSCLC). We aimed to investigate the ability of Radiomics applied to computed tomography (CT) in predicting PD-L1 expression in patients with advanced NSCLC. METHODS: By applying texture analysis, we retrospectively analyzed 72 patients with advanced NSCLC. The datasets were randomly split into a training cohort (2/3) and a validation cohort (1/3). Forty radiomic features were extracted by manually drawing tumor volumes of interest (VOIs) on baseline contrast-enhanced CT. After selecting features on the training cohort, two predictive models were created using binary logistic regression, one for PD-L1 values ≥ 50% and the other for values between 1 and 49%. The two models were analyzed with ROC curves and tested in the validation cohort. RESULTS: The Radiomic Score (Rad-Score) for PD-L1 values ≥ 50%, which consisted of Skewness and Low Gray-Level Zone Emphasis (GLZLM_LGZE), presented a cut-off value of - 0.745 with an area under the curve (AUC) of 0.811 and 0.789 in the training and validation cohort, respectively. The Rad-Score for PD-L1 values between 1 and 49% consisted of Sphericity, Skewness, Conv_Q3 and Gray Level Non-Uniformity (GLZLM_GLNU), showing a cut-off value of 0.111 with AUC of 0.763 and 0.806 in the two population, respectively. CONCLUSION: Rad-Scores obtained from CT texture analysis could be useful for predicting PD-L1 expression and guiding the therapeutic choice in patients with advanced NSCLC.

Role of CT angiography in detecting acute pulmonary embolism associated with COVID-19 pneumonia.

PURPOSE: Recently coronavirus disease (COVID-19) caused a global pandemic, characterized by acute respiratory distress syndrome (ARDS). The aim of our study was to detect pulmonary embolism (PE) in patients with severe form of COVID-19 infection using pulmonary CT angiography, and its associations with clinical and laboratory parameters. METHODS: From March to December 2020, we performed a prospective monocentric study collecting data from 374 consecutive patients with confirmed SARS-CoV-2 infection, using real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) assay of nasopharyngeal swab specimens. We subsequently selected patients with at least two of the following inclusion criteria: (1) severe acute respiratory symptoms (such as dyspnea, persistent cough, fever > 37.5 °C, fatigue, etc.); (2) arterial oxygen saturation ≤ 93% at rest; (3) elevated D-dimer (≥ 500 ng/mL) and C-reactive protein levels (≥ 0.50 mg/dL); and (4) presence of comorbidities. A total of 63/374 (17%) patients met the inclusion criteria and underwent CT angiography during intravenous injection of iodinated contrast agent (Iomeprol 400 mgI/mL). Statistical analysis was performed using Wilcoxon rank-sum and Chi-square tests. RESULTS: About, 26/60 patients (40%) were found positive for PE at chest CT angiography. In these patients, D-dimer and CRP values were significantly higher, while a reduction in SaO2 < 93% was more common than in patients without PE (P < 0.001). Median time between illness onset and CT scan was significantly longer (15 days; P < 0.001) in patients with PE. These were more likely to be admitted to the Intensive Care Unit (19/26 vs. 11/34 patients; P < 0.001) and required mechanical ventilation more frequently than those without PE (15/26 patients vs. 9/34 patients; P < 0.001). Vascular enlargement was significantly more frequent in patients with PE than in those without (P = 0.041). CONCLUSIONS: Our results pointed out that patients affected by severe clinical features of COVID-19 associated with comorbidities and significant increase of D-dimer levels developed acute mono- or bi-lateral pulmonary embolism in 40% of cases. Therefore, the use of CT angiography rather than non-contrast CT should be considered in these patients, allowing a better evaluation, that can help the management and improve the outcomes.

Tocilizumab effects in COVID-19 pneumonia: role of CT texture analysis in quantitative assessment of response to therapy.

PURPOSE: To evaluate CT and laboratory changes in COVID-19 patients treated with tocilizumab, compared to a control group, throughout a combined semiquantitative and texture analysis of images. MATERIALS AND METHODS: From March 11 to April 20, 2020, 57 SARS-CoV-2 positive patients were retrospectively compared: group T (n = 30) receiving tocilizumab and group non-T (n = 27) undergoing only antivirals/antimalarials. Chest-CT and laboratory findings were analyzed before and after treatment. CT evaluation included both semiquantitative scoring and texture analysis of all parenchymal lesions. Survival and recovery analyses were also provided with Kaplan-Meier method. RESULTS: In group T, no significant differences were found for CT score after treatment, while several texture features significantly changed, including mean attenuation (p < 0.0001), skewness (p < 0.0001), entropy (p = 0.0146) and higher-order parameters, suggesting considerable fading of parenchymal lesions. PaO2/FiO2 mean value significantly increased after treatment, from 240 ± 93 to 363 ± 107 (p = 0.0003), with parallel decrease in inflammatory biomarkers (CRP, D-dimer and LDH). In group non-T, CT scoring, texture and laboratory parameters showed significant worsening at follow-up. Findings were clinically associated with opposite trends between two groups, with reduction of severe cases in group T (from 21/30 to 5/30; p < 0.0001) as compared to a significant worsening in group non-T (severe cases increasing from 6/27 to 14/27; p = 0.0473). Probability of discharge was significantly higher in group T (p < 0.0001), as well as survival rate, although not statistically significant. CONCLUSIONS: Our results suggest the potential role of CT texture analysis for assessing response to treatment in COVID-19 pneumonia, using Tocilizumab, as compared to semiquantitative evaluation, providing insight into the intrinsic parenchymal changes.

Chest CT score in COVID-19 patients: correlation with disease severity and short-term prognosis.

OBJECTIVES: To correlate a CT-based semi-quantitative score of pulmonary involvement in COVID-19 pneumonia with clinical staging of disease and laboratory findings. We also aimed to investigate whether CT findings may be predictive of patients' outcome. METHODS: From March 6 to March 22, 2020, 130 symptomatic SARS-CoV-2 patients were enrolled for this single-center analysis and chest CT examinations were retrospectively evaluated. A semi-quantitative CT score was calculated based on the extent of lobar involvement (0:0%; 1, < 5%; 2:5-25%; 3:26-50%; 4:51-75%; 5, > 75%; range 0-5; global score 0-25). Data were matched with clinical stages and laboratory findings. Survival curves and univariate and multivariate analyses were performed to evaluate the role of CT score as a predictor of patients' outcome. RESULTS: Ground glass opacities were predominant in early-phase (≤ 7 days since symptoms' onset), while crazy-paving pattern, consolidation, and fibrosis characterized late-phase disease (> 7 days). CT score was significantly higher in critical and severe than in mild stage (p < 0.0001), and among late-phase than early-phase patients (p < 0.0001). CT score was significantly correlated with CRP (p < 0.0001, r = 0.6204) and D-dimer (p < 0.0001, r = 0.6625) levels. A CT score of ≥ 18 was associated with an increased mortality risk and was found to be predictive of death both in univariate (HR, 8.33; 95% CI, 3.19-21.73; p < 0.0001) and multivariate analysis (HR, 3.74; 95% CI, 1.10-12.77; p = 0.0348). CONCLUSIONS: Our preliminary data suggest the potential role of CT score for predicting the outcome of SARS-CoV-2 patients. CT score is highly correlated with laboratory findings and disease severity and might be beneficial to speed-up diagnostic workflow in symptomatic cases. KEY POINTS: • CT score is positively correlated with age, inflammatory biomarkers, severity of clinical categories, and disease phases. • A CT score ≥ 18 has shown to be highly predictive of patient's mortality in short-term follow-up. • Our multivariate analysis demonstrated that CT parenchymal assessment may more accurately reflect short-term outcome, providing a direct visualization of anatomic injury compared with non-specific inflammatory biomarkers.

Standards for European training requirements in interventional neuroradiology : Guidelines by the Division of Neuroradiology/Section of Radiology European Union of Medical Specialists (UEMS), in cooperation with the Division of Interventional Radiology/UEMS, the European Society of Neuroradiology (ESNR), and the European Society of Minimally Invasive Neurological Therapy (ESMINT).

This document sets out standards for training in Interventional Neuroradiology (INR) in Europe. These standards have been developed by a working group of the European Society of Neuroradiology (ESNR) and the European Society of Minimally Invasive Neurological Therapy (ESMINT) on the initiative and under the umbrella of the Division of Neuroradiology/Section of Radiology of the European Union of Medical Specialists (UEMS).

Influence of residential land cover on childhood allergic and respiratory symptoms and diseases: Evidence from 9 European cohorts.

INTRODUCTION: Recent research focused on the interaction between land cover and the development of allergic and respiratory disease has provided conflicting results and the underlying mechanisms are not fully understood. In particular, green space, which confers an overall positive impact on general health, may be significantly contributing to adverse respiratory health outcomes. This study evaluates associations between surrounding residential land cover (green, grey, agricultural and blue space), including type of forest cover (deciduous, coniferous and mixed), and childhood allergic and respiratory diseases. METHODS: Data from 8063 children, aged 3-14 years, were obtained from nine European population-based studies participating in the HEALS project. Land-cover exposures within a 500 m buffer centred on each child's residential address were computed using data from the Coordination of Information on the Environment (CORINE) program. The associations of allergic and respiratory symptoms (wheeze, asthma, allergic rhinitis and eczema) with land coverage were estimated for each study using logistic regression models, adjusted for sex, age, body mass index, maternal education, parental smoking, and parental history of allergy. Finally, the pooled effects across studies were estimated using meta-analyses. RESULTS: In the pooled analyses, a 10% increase in green space coverage was significantly associated with a 5.9%-13.0% increase in the odds of wheezing, asthma, and allergic rhinitis, but not eczema. A trend of an inverse relationship between agricultural space and respiratory symptoms was observed, but did not reach statistical significance. In secondary analyses, children living in areas with surrounding coniferous forests had significantly greater odds of reporting wheezing, asthma and allergic rhinitis. CONCLUSION: Our results provide further evidence that exposure to green space is associated with increased respiratory disease in children. Additionally, our findings suggest that coniferous forests might be associated with wheezing, asthma and allergic rhinitis. Additional studies evaluating both the type of green space and its use in relation to respiratory conditions should be conducted in order to clarify the underlying mechanisms behind associated adverse impacts.

SIRM-SIAAIC consensus, an Italian document on management of patients at risk of hypersensitivity reactions to contrast media.

Hypersensitivity reactions (HRs) to contrast media (CM) can be distinguished in immune-mediated (including allergic reactions) and non-immune-mediated reactions, even if clinical manifestations could be similar. Such manifestations range from mild skin eruptions to severe anaphylaxis, making it important for radiologists to know how to identify and manage them. A panel of experts from the Società Italiana di Radiologia Medica e Interventistica (SIRM) and the Società Italiana di Allergologia, Asma e Immunologia Clinica (SIAAIC) provided a consensus document on the management of patients who must undergo radiological investigations with CM. Consensus topics included: the risk stratification of patients, the identification of the culprit CM and of a safe alternative by an allergy workup, as well as the use of premedication and the correct procedure to safely perform an elective (i.e., scheduled) or urgent examination. The most important recommendations are: (1) in all patients, a thorough medical history must be taken by the prescribing physician and/or the radiologist to identify at-risk patients; (2) in patients with hypersensitivity reactions to CM, the radiologist must consider an alternative, non-contrast imaging study with a comparable diagnostic value, or prescribe a different investigation with another class of CM; (3) if such options are not feasible, the radiologist must address at-risk patients to a reference centre for an allergy evaluation; (4) if timely referral to an allergist is not viable, it is recommended to use a CM other than the responsible one, taking into account cross-reactivity patterns; in the case of patients with histories of severe reactions, the presence of an anesthesiologist is also recommended and a premedication is suggested.

[Excess mortality risk in nursing care homes before and during the COVID-19 outbreak in Mantua and Cremona provinces (Lombardy Region, Northern Italy)]. / L'eccesso di rischio di morte nelle residenze sanitarie assistenziali prima e durante l'epidemia di COVID-19 nelle province di Mantova e Cremona.

OBJECTIVES: 1. to evaluate mortality risk excess in the population residing in nursing care homes (NCHs) compared to non-NCHs before the COVID-19 outbreak; 2. to verify if the outbreak modified risk excess; 3. to estimate the COVID-19 impact; 4. to ascertain incidence-mortality relationship. DESIGN: cohort study. SETTING AND POPULATION: Mantua and Cremona provinces (Lombardy Region, Northern Italy) - included in ATS Val Padana - with COVID-19 incidence rate 7.5‰ and 16.9‰, respectively. Inhabitants aged >= 75 years as of 1st January 2018, 2019, and 2020 (three cohorts), stratified in NCH or not. The indicators calculated were: 1. rate ratio (RR) for NCH vs non-NCH, adjusted by gender, age, chronic diseases number, at least 1 hospitalisation, at least 1 Emergency room access in the previous year, for 2018, 2019, and 2020; 2. adjusted RR, 2019 and 2020 vs 2018, both sub-cohorts (i.e., NCH and non-NCH). MAIN OUTCOME MEASURES: first four-month period mortality of the considered years. RESULTS: aproximately 100,000 inhabitants by year, 7% in NCH. In the 2020 first four-month period, 4,343 deaths occurred of which 45% in NCH. RR in NCH population vs non-NCH for the year 2018 was 2.13 (95%CI 1.94-2.34); for the year 2019 was 2.70 (95%CI 2.43-3.00); for the year 2020 was 6.98 (95%CI 6,49-7,50). Adjusted RR for NCH population in 2020 vs 2018 was 2.22 (95%CI 2.05-2.42) in the whole ATS Val Padana; 1.58 (95%CI 1.40-1.77) in Mantua Province; 2.93 (2.62-3.27) in Cremona Province. Adjusted RR in non-NCH population in the year 2020 vs 2018 was 1.59 (95%CI 1.48-1.70) in the whole ATS; 1.34 (95%CI 1.23-1.46) in Mantua Province; 1.89 (95%CI 1.73-2.07) in Cremona Province. CONCLUSIONS: the NCH population experienced an excess risk mortality compared to non-NCH before the COVID-19; this excess increased during the outbreak. In 2020, in NCHs the risk was more than double compared to the 2018 risk, while in non-NCHs it rose approximately by 60%. The gap between NCHs/non-NCHs COVID-19 impact was higher in Cremona than in Mantua.