The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.

Mechanism for the activation of the anaplastic lymphoma kinase receptor.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that regulates important functions in the central nervous system1,2. The ALK gene is a hotspot for chromosomal translocation events that result in several fusion proteins that cause a variety of human malignancies3. Somatic and germline gain-of-function mutations in ALK were identified in paediatric neuroblastoma4-7. ALK is composed of an extracellular region (ECR), a single transmembrane helix and an intracellular tyrosine kinase domain8,9. ALK is activated by the binding of ALKAL1 and ALKAL2 ligands10-14 to its ECR, but the lack of structural information for the ALK-ECR or for ALKAL ligands has limited our understanding of ALK activation. Here we used cryo-electron microscopy, nuclear magnetic resonance and X-ray crystallography to determine the atomic details of human ALK dimerization and activation by ALKAL1 and ALKAL2. Our data reveal a mechanism of RTK activation that allows dimerization by either dimeric (ALKAL2) or monomeric (ALKAL1) ligands. This mechanism is underpinned by an unusual architecture of the receptor-ligand complex. The ALK-ECR undergoes a pronounced ligand-induced rearrangement and adopts an orientation parallel to the membrane surface. This orientation is further stabilized by an interaction between the ligand and the membrane. Our findings highlight the diversity in RTK oligomerization and activation mechanisms.

HIV reservoir and premature aging: risk factors for aging-associated illnesses in adolescents and young adults with perinatally acquired HIV.

Despite receiving antiretroviral therapy (ART), an increasing number of adolescents and young adults with perinatally acquired HIV (PHIVAYA) are at risk of developing premature senescence and aging-associated illnesses, including cancer. Given this concern, it is crucial to assess aging biomarkers and their correlation with the HIV reservoir in order to comprehensively characterize and monitor these individuals. Fifty-five PHIVAYA (median age: 23, interquartile range [IQR]: 20-27 years, and 21 [18-23] years on ART at the time of study sampling) were studied along with 23 age-matched healthy controls. The PHIVAYA exhibited significantly higher percentages of activated, senescent, exhausted CD4 and CD8 T cells, shorter telomeres, reduced thymic output, and higher levels of circulating inflammatory markers (PAMPs, DAMPs, and pro-inflammatory cytokines IL-6, IL-8, and TNFα) as well as denervation biomarkers (neural cell adhesion molecule 1 [NCAM1] and C-terminal Agrin fragment [CAF]), compared to controls. HIV-DNA levels positively correlated with activated, senescent, exhausted CD4 and CD8 T cells, circulating biomarkers levels, and inversely with regulatory T and B cells and telomere length. According to their viremia over time, PHIVAYA were subgrouped into 14 Not Suppressed (NS)-PHIVAYA and 41 Suppressed (S)-PHIVAYA, of whom 6 who initiated ART within one year of age and maintained sustained viral suppression overtime were defined as Early Suppressed (ES)-PHIVAYA and the other 35 as Late Suppressed (LS)-PHIVAYA. ES-PHIVAYA exhibited significantly lower HIV-DNA reservoir, decreased percentages of senescent and exhausted CD4 and CD8 T cells, reduced levels of circulating inflammatory and denervation biomarkers, but longer telomere compared to LS- and NS-PHIVAYA. They differed significantly from healthy controls only in a few markers, including higher percentages of regulatory T and B cells, and higher levels of DAMPs. Overall, these results underscore the importance of initiating ART early and maintaining viral suppression to limit the establishment of the viral reservoir and to counteract immune and cellular premature aging. These findings also suggest new approaches for minimally invasive monitoring of individuals at high risk of developing premature aging and age-related illnesses.

Differences in survival and recurrence of colorectal cancer by stage across population-based European registries.

Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age-standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method. The proportion of nonmetastatic resected colorectal cancers varied from 58.6% to 78.5% according to countries. The overall 5-year net survival by country ranged between 60.8% and 74.5%. The absolute difference between the 5-year survival extremes was 12.8 points for stage II (Bulgaria vs Switzerland), 19.7 points for stage III (Bulgaria vs. Switzerland) and 14.8 points for Stage IV and unresected cases (Bulgaria vs. Switzerland or France). Five-year cumulative rate of recurrence among resected patients with stage I-III was 17.7%. As compared to the mean of the whole cohort, the risk of developing a recurrence did not differ between countries except a lower risk in Italy for both stage I/II and stage III cancers and a higher risk in Spain for stage III. Survival after colorectal cancer differed across the concerned European countries while there were slight differences in recurrence rates. Population-based collection of cancer recurrence information is crucial to enhance efforts for evidence-based management of colorectal cancer follow up.

Multi-modal immune dynamics of pre-COVID-19 Kawasaki Disease following intravenous immunoglobulin.

Despite progress, the molecular mechanisms underlying Kawasaki Disease (KD) and intravenous immunoglobulin's (IVIG) ability to mitigate the inflammatory process remain poorly understood. To characterize this condition, plasma proteomic profiles, flow cytometry, and gene expression of T cell subsets were investigated in longitudinal samples from KD patients and compared with two control groups. Systems-level analysis of samples in the acute phase revealed distinctive inflammatory features of KD, involving mainly Th-1 and Th-17 mediators and unveiled a potential disease severity signature. APBB1IP demonstrated an association with coronary artery involvement (CAI) and was significantly higher in CAI+ compared to CAI- patients. Integrative analysis revealed a transient reduction in CD4+ EM T cells and a comprehensive immune activation and exhaustion. Following treatment, Tregs at both frequency and gene expression levels revealed immune dynamics of recovery. Overall, our data provide insights into KD, which may offer valuable information on prognostic indicators and possible targets for novel treatments.

Treatment of giant cell arteritis with ultra-short glucocorticoids and tocilizumab: the role of imaging in a prospective observational study.

OBJECTIVES: To assess the impact of tocilizumab (TCZ) monotherapy after ultra-short-pulse glucocorticoids (GCs) on clinical manifestations, and vessel inflammation and damage in large vessel-GCA (LV-GCA). METHODS: In this prospective observational study, we enrolled patients with active LV-GCA. All patients received 500 mg per day i.v. methylprednisolone for three consecutive days and weekly s.c. TCZ injections from day 4 until week 52. PET/CT was performed on all patients at baseline and at weeks 24 and 52. The primary end points were the reduction in the PET vascular activity score (PETVAS) at weeks 24 and 52 compared with baseline, and the proportion of patients with relapse-free remission at weeks 24 and 52. The secondary end point was the proportion of patients with new aortic dilation at weeks 24 and 52. RESULTS: A total of 18 patients were included (72% female, mean age 68.5 years). Compared with the baseline value, a significant reduction in the PETVAS was observed at weeks 24 and 52, mean (95% CI) reductions -8.6 (-11.5 to -5.7) and -10.4 (-13.6 to -7.2), P = 0.001 and 0.002, respectively. The proportion of patients with relapse-free remission at weeks 24 and 52 was 10/18 (56%, 95% CI 31-78) and 8/17 (47%, 95% CI 23-72), respectively. At weeks 24 and 52, no patient had shown new aortic dilation. However, 4 patients who had shown aortic dilation at baseline showed a significant increase in aortic diameter (≥5 mm) at week 52. CONCLUSION: TCZ monotherapy after ultra-short-pulse GCs controlled the clinical symptoms of GCA and reduced vascular inflammation. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05394909.

Treatment of giant cell arteritis with ultra-short glucocorticoids and tocilizumab: results from the extension of the TOPAZIO study.

OBJECTIVES: To assess the maintenance of efficacy of one year of tocilizumab (TCZ) monotherapy after its discontinuation in large vessel-GCA (LV-GCA). METHODS: 17 patients with active LV-GCA were previously treated with 3 boluses of intravenous methylprednisone and weekly subcutaneous TCZ in monotherapy for 52 weeks. Patients in relapse-free clinical remission at week 52 discontinued TCZ and entered part two, which was a 26-week observational follow-up period. PET/CT was performed in all patients at the end of the 26-week observational period (week 78). End points were the variation in PET vascular activity score (PETVAS) at week 78 compared with baseline and with week 52, and the proportion of patients with relapse-free clinical remission at week 78 and at the end of the follow-up. RESULTS: Compared with baseline, a significant reduction in PETVAS was observed at week 78, mean (95% CI) change -6.6 (-9.5 to -3.7). However, compared with week 52, PETVAS significantly increase 6 months after TCZ discontinuation (week 78), mean (95% CI) change 4.6 (0.7-8.5). The proportion of patients with relapse-free clinical remission at weeks 78 and at the end of the follow-up (median time from TCZ discontinuation 148 weeks) was 11/17 (65%, 95% CI 38-86) and 8/17 (47%, 95% CI 23-72), respectively. Age and sex-adjusted HR (95% CI) for each unit increase of PETVAS indicating subsequent relapse was 1.36 (0.92-2.00). CONCLUSIONS: One year of TCZ monotherapy was effective in maintaining drug-free clinical remission in LV-GCA. Changes in PETVAS early after TCZ discontinuation may predict subsequent relapses. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05394909.

Accuracy of World Health Organisation-grade parameters (necrosis and mitotic activity) and foci of vascular invasion in predicting prognosis of papillary thyroid carcinoma. A case-control validation study.

AIMS: Tumour necrosis and/or increased mitoses define high-grade papillary thyroid carcinoma (PTC). It is unclear whether angioinvasion is prognostic for PTC. Cut-offs at five or more mitoses/2 mm2 and four or more angioinvasive foci have been empirically defined based upon data from all forms of aggressive non-anaplastic thyroid carcinomas. Performance of tumour necrosis, mitoses and vascular invasion in predicting distant metastases when specifically applied to PTC is undefined. METHODS: We analysed 50 consecutive PTC cases with distant metastases (DM-PTC): 16 synchronous and 34 metachronous. A total of 108 non-metastatic PTC (N-DM-PTC, 15.0-year median follow-up) were used as controls. Invasive encapsulated follicular variant PTC was excluded. Necrosis, mitoses and angioinvasion were quantified. Receiver operating characteristics (ROC) and area under the curve (AUC) analyses determined best sensitivity and specificity cut-offs predictive of distant metastases. RESULTS: Metastases correlated with necrosis (any extent = 43.8% all DM-PTC, 53.1% metachronous DM-PTC versus 5% N-DM-PTC; P < 0.001), mitoses (P < 0.001) and angioinvasion (P < 0.001). Mitoses at five or more per 2 mm2 was the best cut-off correlating with distant metastases: sensitivity/specificity 42.9%/97.2% all DM-PTC (AUC = 0.78), 18.8%/97.2% synchronous DM-PTC (AUC = 0.63), 54.6%/97.2% metachronous DM-PTC (AUC = 0.85). Angioinvasive foci at five or more was the best cut-off correlating with distant metastases: sensitivity/specificity 36.2%/91.7% all DM-PTC (AUC = 0.75), 25%/91.7% synchronous DM-PTC (AUC = 0.79) and 41.9%/91.7% metachronous DM-PTC (AUC = 0.73). Positive/negative predictive values (PPV/NPV) were: necrosis 22.6%/98.2%; five or more mitoses 32.3%/98.2%; five or more angioinvasive foci 11.8%/97.9%. After multivariable analysis, only necrosis and mitotic activity remained associated with DM-PTC. CONCLUSION: Our data strongly support PTC grading, statistically validating World Health Organisation (WHO) criteria to identify poor prognosis PTC. Angioinvasion is not an independent predictor of DM-PTC.

CCL18, CHI3L1, ANG2, IL-6 systemic levels are associated with the extent of lung damage and radiomic features in SARS-CoV-2 infection.

OBJECTIVE AND DESIGN: We aimed to identify cytokines whose concentrations are related to lung damage, radiomic features, and clinical outcomes in COVID-19 patients. MATERIAL OR SUBJECTS: Two hundred twenty-six patients with SARS-CoV-2 infection and chest computed tomography (CT) images were enrolled. METHODS: CCL18, CHI3L1/YKL-40, GAL3, ANG2, IP-10, IL-10, TNFα, IL-6, soluble gp130, soluble IL-6R were quantified in plasma samples using Luminex assays. The Mann-Whitney U test, the Kruskal-Wallis test, correlation and regression analyses were performed. Mediation analyses were used to investigate the possible causal relationships between cytokines, lung damage, and outcomes. AVIEW lung cancer screening software, pyradiomics, and XGBoost classifier were used for radiomic feature analyses. RESULTS: CCL18, CHI3L1, and ANG2 systemic levels mainly reflected the extent of lung injury. Increased levels of every cytokine, but particularly of IL-6, were associated with the three outcomes: hospitalization, mechanical ventilation, and death. Soluble IL-6R showed a slight protective effect on death. The effect of age on COVID-19 outcomes was partially mediated by cytokine levels, while CT scores considerably mediated the effect of cytokine levels on outcomes. Radiomic-feature-based models confirmed the association between lung imaging characteristics and CCL18 and CHI3L1. CONCLUSION: Data suggest a causal link between cytokines (risk factor), lung damage (mediator), and COVID-19 outcomes.

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.

Health knowledge after stroke in Switzerland: a survey among health professionals on current practice and suggestions for the implementation of a technology-based educational program for stroke survivors.

BACKGROUND: It is estimated that 1 in 4 stroke survivors will experience a second stroke. Educating patients about risk factors for stroke and a generally healthier lifestyle may help prevent recurrent strokes, which are a burden on society and the healthcare system. The goals of this paper were to investigate the estimated level of knowledge of stroke patients regarding their disease, the methods of information commonly used in clinical practice, the topics that should be included in an educational program aimed at improving health knowledge among stroke survivors, and how such a program could be delivered with the help of technology-based education (i.e., information delivered by digital platforms such as smartphones or rehabilitation technologies). METHODS: We performed a survey among health professionals working with stroke patients in Switzerland. RESULTS: 161 health professionals of different backgrounds took part in the survey, and 94 completed it. According to the results, only 33% of healthcare professionals thought that patients were well informed about stroke one month after stroke onset. These findings suggest that there is room for improvement in how stroke patients are educated about stroke, risk factors, and prevention. Additionally, it was highlighted that technology is not commonly used in clinical practice to support patients' education, although this is an acceptable method for healthcare professionals. The results also helped to identify key topics to be included in an educational program and recommendations for implementing such a program in rehabilitation technologies. CONCLUSIONS: This work allowed gaining more insight into healthcare professionals' opinions on the potential of technology-based education and key aspects to consider when implementing it to support health and prevention knowledge after stroke.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

Unsupervised robot-assisted rehabilitation after stroke: feasibility, effect on therapy dose, and user experience.

BACKGROUND: Unsupervised robot-assisted rehabilitation is a promising approach to increase the dose of therapy after stroke, which may help promote sensorimotor recovery without requiring significant additional resources and manpower. However, the unsupervised use of robotic technologies is not yet a standard, as rehabilitation robots often show low usability or are considered unsafe to be used by patients independently. In this paper we explore the feasibility of unsupervised therapy with an upper limb rehabilitation robot in a clinical setting, evaluate the effect on the overall therapy dose, and assess user experience during unsupervised use of the robot and its usability. METHODS: Subacute stroke patients underwent a four-week protocol composed of daily 45 min-sessions of robot-assisted therapy. The first week consisted of supervised therapy, where a therapist explained how to interact with the device. The second week was minimally supervised, i.e., the therapist was present but intervened only if needed. After this phase, if participants learnt how to use the device, they proceeded to two weeks of fully unsupervised training. Feasibility, dose of robot-assisted therapy achieved during unsupervised use, user experience, and usability of the device were evaluated. Questionnaires to evaluate usability and user experience were performed after the minimally supervised week and at the end of the study, to evaluate the impact of therapists' absence. RESULTS: Unsupervised robot-assisted therapy was found to be feasible, as 12 out of the 13 recruited participants could progress to unsupervised training. During the two weeks of unsupervised therapy participants on average performed an additional 360 min of robot-assisted rehabilitation. Participants were satisfied with the device usability (mean System Usability Scale scores > 79), and no adverse events or device deficiencies occurred. CONCLUSIONS: We demonstrated that unsupervised robot-assisted therapy in a clinical setting with an actuated device for the upper limb was feasible and can lead to a meaningful increase in therapy dose. These results support the application of unsupervised robot-assisted therapy as a complement to usual care in clinical settings and pave the way to its application in home settings. TRIAL REGISTRATION: Registered on 13.05.2020 on clinicaltrials.gov (NCT04388891).

Italian guidelines for age range and test interval in breast cancer screening programmes: GRADE-ADOLOPMENT of the European guidelines.

A guideline panel formulated a set of recommendations for breast cancer screening and diagnosis to implement clinical activities in Italy in alignment with the European Breast Cancer Guidelines on Screening and Diagnosis (European Commission Initiative on Breast Cancer-ECIBC). The panel issued national recommendations through adopting, adapting, and/or developing recommendations from the European guidelines (ADOLOPMENT approach). This process utilizes the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence to decision (EtD) framework. An additional PubMed search was conducted using search terms specific to Italy to tailor the EU guidelines to the national context. Nine articles were included as contextual evidence in the EtD. A total of 13 recommendations were finalized, either adapted or adopted to suit the national context. Organized breast cancer screening is strongly recommended for women aged 50-69 every 2 years, and it is conditionally recommended every 3 years for women aged 70-74, as well as every 1 or 2 years for women aged 45-49. Annual mammography received a strong recommendation against for women aged 50 and older. Developing shared national guidelines for the management of mammography screening will improve the standardization of processes across all settings, thereby promoting health equity.

Budget impact analysis of introducing digital breast tomosynthesis in breast cancer screening in Italy.

PURPOSE: This study quantifies the impact on budget and cost per health benefit of implementing digital breast tomosynthesis (DBT) in place of digital mammography (DM) for breast cancer screening among asymptomatic women in Italy. METHODS: A budget impact analysis and a cost consequence analysis were conducted using parameters from the MAITA project and literature. The study considered four scenarios for DBT implementation, i.e., DBT for all women, DBT for women aged 45-49 years, DBT based on breast density (BI-RADS C + D or D only), and compared these to the current DM screening. Healthcare provider's perspective was adopted, including screening, diagnosis, and cancer treatment costs. RESULTS: Introducing DBT for all women would increase overall screening costs by 20%. Targeting DBT to women aged 45-49 years or with dense breasts would result in smaller cost increases (3.2% for age-based and 1.4-10.7% for density-based scenarios). The cost per avoided interval cancer was significantly higher when DBT was applied to all women compared to targeted approaches. The cost per gained early-detected cancer slightly increases in targeted approaches, while the assumptions on the clinical significance and overdiagnosis of cancers detected by DBT and not by DM have a strong impact. CONCLUSIONS: Implementing DBT as a primary breast cancer test in screening programs in Italy would lead to a substantial increase in costs. Tailoring DBT use to women aged 45-49 or with dense breasts could enhance the feasibility and sustainability of the intervention. Further research is needed to clarify the impact of DBT on overdiagnosis and the long-term outcomes.

Organizational impact of systemic implementation of digital breast tomosynthesis as a primary test for breast cancer screening in Italy.

PURPOSE: We present a comprehensive investigation into the organizational, social, and ethical impact of implementing digital breast tomosynthesis (DBT) as a primary test for breast cancer screening in Italy. The analyses aimed to assess the feasibility of DBT specifically for all women aged 45-74, women aged 45-49 only, or those with dense breasts only. METHODS: Questions were framed according to the European Network of Health Technology Assessment (EuNetHTA) Screening Core Model to produce evidence for the resources, equity, acceptability, and feasibility domains of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) decision framework. The study integrated evidence from the literature, the MAITA DBT trials, and Italian pilot programs. Structured interviews, surveys, and systematic reviews were conducted to gather data on organizational impact, acceptability among women, reading and acquisition times, and the technical requirements of DBT in screening. RESULTS: Implementing DBT could significantly affect the screening program, primarily due to increased reading times and the need for additional human resources (radiologists and radiographers). Participation rates in DBT screening were similar, if not better, to those observed with standard digital mammography, indicating good acceptability among women. The study also highlighted the necessity for specific training for radiographers. The interviewed key persons unanimously considered feasible tailored screening strategies based on breast density or age, but they require effective communication with the target population. CONCLUSIONS: An increase in radiologists' and radiographers' workload limits the feasibility of DBT screening. Tailored screening strategies may maximize the benefits of DBT while mitigating potential challenges.

[Differences between Italians and immigrants in COVID-19 vaccination coverage in the Reggio Emilia resident population (Emilia-Romagna Region, Northern Italy)]. / Analisi delle disuguaglianze nelle coperture del vaccino anti-COVID-19 tra italiani e immigrati nella popolazione residente a Reggio Emilia.

The present work describes the cumulative coverage curves by country of birth, sex, age, and area of residence of the adult population residing in the province of Reggio Emilia (Emilia-Romagna Region, Northern Italy).The analyses are stratified by country of birth into HDC (Highly Developed Country), mostly Italians, and HMPC (Highly Migration Pressure Country), as a proxy of migrant status, excluding deaths. Vaccinations carried out up to September 2022 and recorded in the information system were considered, including vaccinations performed outside the province. Vaccinations done abroad are not included when the information is incomplete or the type of vaccine is different from those administered in Italy.Vaccination coverage (%) by number of doses and estimated Hazard Ratio (HR) and related 95% confidence intervals (95%CI) are calculated using Cox models, adjusted for age and stratified by sex.A lower vaccination coverage was detected, delayed by a few weeks, among HMPC, but the differences in vaccination coverage are reversed when the different age structure of the two populations is taken into account. From the estimates of the Cox models, a higher propensity to vaccinate was noted among immigrants, in particular among women (women HR: 1.65; CI95% 1.52-1.78; men HR: 1.39; CI95% 1.28-1.52). Women were vaccinated first, but, at the end of the observation period, there were no particular differences in coverage between the two sexes, either among Italians or immigrants. Focusing on the area of origin, a strong propensity for vaccination was noted, particularly among who came from North Africa. In the mountain areas of the province, a lower propensity for vaccination was observed, perhaps explained by the greater distance of the vaccination centers or by a lower acceptability of the vaccine.

[Reducing the impact of COVID-19 in immigrants: a systematic review of the efficacy of interventions]. / Contenimento della diffusione del COVID-19 nella popolazione immigrata: una revisione sistematica dell'efficacia degli interventi.

BACKGROUND: the spread of SARS-CoV-2 in the population has amplified the effects of health inequalities, particularly in the most vulnerable groups such as immigrants and refugees. An assessment of the intervention to contain the COVID-19 in these population groups was essential to define new strategies for more equitable, inclusive, and effective health policies to on health. OBJECTIVES: to provide a systematic synopsis of the impact of interventions to contain the spread of SARS-CoV-2 in immigrants. METHODS: data sources included major bibliographic databases. Using a study protocol, already shared with the international scientific community, two independent researchers reviewed the citations, selected and evaluated the interventions studies. Due to the heterogeneity of the interventions, a narrative synthesis was carried out. RESULTS: three eligible studies were identified. The first study modelled the incidence of the disease in a refugee camp in Greece, based on an intervention of sectorialization of people that accessed to services, the use of masks, the early identification and isolation of cases and their family members, and the limitation of movements within the camp. The second evaluated the impact of preventive pharmacological interventions such as the use of hydroxychloroquine, ivermectin, povidone-iodine, zinc, and vitamin C, in different dosages and combinations, to a group of immigrant workers in a city dormitory in Singapore. The third study evaluated an intervention to increase vaccination coverage within a Latino immigrant community in the United States, moving the location of vaccine supply throughout the most frequented contexts by the immigrant community to access the city services. The results of the first and second studies suggest impacts for some of the proposed interventions even if they have been partially overcome due to the use of mass vaccination. The third showed a reduction in vaccine hesitancy and an increase in vaccination uptake and a snowball effect. CONCLUSIONS: the systematic review identified few heterogeneous studies, preventing any generalization of the results. Probably, the low scientific production does not reflect the successful experiences implemented. In the case of a possible resumption of the epidemic or new emergencies, it will be necessary to rely on indirect evidence and the scientific community should consider more the responsibility to evaluate and make available the experiences gained in the field. A constant monitoring activity of the evidence that will be necessary to updating the results for suggest consolidated prevention measures to for controlling the incidence of COVID-19 in immigrants during a possible resumption of the epidemic and for application in other similarly emergency contexts.

Impact of COVID-19 on foreign population resident in urban areas of Italy: selection of indicators, data sources, and definition of geographical stratification levels / Impatto del COVID-19 negli stranieri residenti nelle aree urbane in Italia: la scelta degli indicatori, delle fonti informative e la definizione dei livelli di stratificazione del territorio.

OBJECTIVES: to describe indicators, data sources, and levels of geographical stratification used within the framework of the CCM project "Epidemiological Surveillance and Control of COVID-19 in Metropolitan Urban Areas and for the containment of SARS-CoV-2 circulation in the immigrant population in Italy". DESIGN: population-based observational study based on data from the Integrated Covid-19 Surveillance System and the archive of hospital discharge records. SETTING AND PARTICIPANTS: interregional collaborative project. Resident population in 5 Italian Regions (Piedmont, Emilia-Romagna, Tuscany, Lazio, and Sicily). MAIN OUTCOMES MEASURES: crude and age-standardized rates of diagnostic test utilization and positivity, hospitalization (in any department and in intensive care unit), and mortality in COVID-19 cases. RESULTS: starting from the set of 11 indicators from the Italian National Institute for Health, Migration and Poverty (INMP) project "Epidemiology of SARS-CoV-2 Infection (COVID-19) and Use of Health Services in the Immigrant Population and Vulnerable Population Groups in Italy", the five most effective indicators for CCM purposes were identified. The INMP project highlighted higher rates of test access and positivity among Italians compared to foreigners, higher standardized hospitalization rates among foreigners, and higher standardized mortality rates among Italians, with geographical and temporal heterogeneity. The intersection between the DEGURBA (degree of urbanisation) classification and altimetric zones defined five levels of territorial stratification characterized by decreasing population density. Approximately 81% of the population involved in the CCM project resided in the first two levels; 43% of Italians lived in areas with intermediate population density in hilly or plain areas, while 48% of foreigners were concentrated in densely populated areas. CONCLUSIONS: sharing the collaborative approach and a research methodology already tested, integrated with the analysis of disaggregated indicators by morphological, functional, and administrative characteristics of the residential territory, allowed for assessing differences in the impact of the pandemic between Italians and foreigners residing in more or less densely populated areas.

[Impact of the SARS-CoV-2 epidemic on the immigrant population by urbanisation degree in five Italian Regions (Piedmont, Emilia-Romagna, Tuscany, Lazio, and Sicily)]. / Impatto dell'epidemia da SARS-CoV-2 nella popolazione immigrata per grado di urbanizzazione in Piemonte, Emilia-Romagna, Toscana, Lazio e Sicilia.

BACKGROUND: according to the literature, socially disadvantaged strata of the population, including immigrants, have been more vulnerable to the risk of SARS-CoV-2 infection due to greater exposure and less opportunity to protect themselves, and to COVID-19 complications due to metabolic and clinical risk factors as well as to healthcare access barriers. Two Italian projects - coordinated by the Italian National Institute for Health, Migration and Poverty and the Italian National Centre for Disease Prevention and Control - set up an epidemiological surveillance to monitor the temporal trends of the SARS-CoV-2 pandemic in five Italian regions using validated indicators. OBJECTIVES: to identify differences between Italians and immigrants in terms of the epidemic evolution and its health consequences, and to investigate possible differences by urbanisation degree and region of residence. DESIGN: cross sectional study. SETTING AND PARTICIPANTS: resident population in five Italian regions: Piedmont, Emilia-Romagna, Tuscany, Lazio, and Sicily. MAIN OUTCOMES MEASURES: frequencies of positive tests, routine hospitalisations, and deaths related to COVID-19 were collected, with respect to the period between 22.02.2020 and 31.01.2021. Data were aggregated by week, region, degree of urbanisation, gender, age (5-year classes), and citizenship (Italian/foreigner). Crude and standardised rates of the outcomes considered were calculated, stratified by gender, citizenship, region, and aggregated by pandemic macro-period. RESULTS: the study population counts approximately about 23 million residents as of 01.01.2020 (9.4% immigrants). During the period of interest, 1,542,458 cases of infection were recorded, whereas hospitalisations amounted to 175,979, and deaths to 44,867. Lower crude rates of hospitalisations and deaths were observed among immigrants compared to Italians. The age-standardised hospitalisation rates, on the other hand, showed an opposite trend and were significantly higher among immigrants, due to the excess observed in urban areas, especially in periods of epidemic peak, both for males (weekly mean standardised rate: 34.6 per 1,000 of foreign residents vs 24.3 of Italians over the period October 2020-January 2021) and females (23.2 vs 15.1 over the period February-April 2021). These differences seem to be more pronounced in the central regions and tend to disappear for residents in scarcely populated areas. Standardised mortality rates were higher among immigrants, both men and women, from October 2020 and more markedly in February-April 2021 among men. CONCLUSIONS: the impact of COVID-19 was stronger among immigrants in relation to hospitalisation, especially during epidemic peak periods and in some regions. The difference in the impact on mortality was smaller. There is some heterogeneity among regions and urban areas that is worth considering in the planning of interventions and integration policies.