Comparison of HPV-positive triage strategies combining extended genotyping with cytology or p16/ki67 dual staining in the Italian NTCC2 study.

BACKGROUND: Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. METHODS: Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. FINDINGS: Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. INTERPRETATION: Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years. FUNDING: Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support.

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.

Comparing accuracy of tomosynthesis plus digital mammography or synthetic 2D mammography in breast cancer screening: baseline results of the MAITA RCT consortium.

AIM: The analyses here reported aim to compare the screening performance of digital tomosynthesis (DBT) versus mammography (DM). METHODS: MAITA is a consortium of four Italian trials, REtomo, Proteus, Impeto, and MAITA trial. The trials adopted a two-arm randomised design comparing DBT plus DM (REtomo and Proteus) or synthetic-2D (Impeto and MAITA trial) versus DM; multiple vendors were included. Women aged 45 to 69 years were individually randomised to one round of DBT or DM. FINDINGS: From March 2014 to February 2022, 50,856 and 63,295 women were randomised to the DBT and DM arm, respectively. In the DBT arm, 6656 women were screened with DBT plus synthetic-2D. Recall was higher in the DBT arm (5·84% versus 4·96%), with differences between centres. With DBT, 0·8/1000 (95% CI 0·3 to 1·3) more women received surgical treatment for a benign lesion. The detection rate was 51% higher with DBT, ie. 2·6/1000 (95% CI 1·7 to 3·6) more cancers detected, with a similar relative increase for invasive cancers and ductal carcinoma in situ. The results were similar below and over the age of 50, at first and subsequent rounds, and with DBT plus DM and DBT plus synthetic-2D. No learning curve was appreciable. Detection of cancers >= 20 mm, with 2 or more positive lymph nodes, grade III, HER2-positive, or triple-negative was similar in the two arms. INTERPRETATION: Results from MAITA confirm that DBT is superior to DM for the detection of cancers, with a possible increase in recall rate. DBT performance in screening should be assessed locally while waiting for long-term follow-up results on the impact of advanced cancer incidence.

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.

Effect of Plasma Unit Weight and Donor Sex on Post-Donation Citrate Level: An Experimental Study on Plasmapheresis Donors.

Introduction: Plasmapheresis donation is considered safe and well tolerated, although long-term effects need to be clarified. The volumes of anticoagulant (ACD-A) used are variable and depend primarily on hematocrit (HCT), total blood processed, amount of plasma collected, and donor characteristics. To elucidate the effect of the plasma unit weight setting on plasmapheresis efficiency and ACD-A distribution, we enrolled male donors undergoing a controlled apheresis process donating 700 g and 720 g in two different sessions. In parallel, we investigated a possible effect of sex, recruiting women donating 700 g of plasma. Methods: The study was conducted on men donating 720 g and (12 months later) 700 g of plasma, and on women donating 700 g of plasma. The main outcomes were pre-/post-donation delta (Δ) citrate concentration in donor plasma and ACD-A reinfused to the donor. Information concerning the annual check-up and the procedure was also collected. Intergroup comparisons (men donating 720 g vs. men donating 700 g and men vs. women both donating 700 g) and intragroup associations with donor and procedural characteristics were reported. Results: With the procedure set at 720 g, the machine processed around 44 mL more whole blood to collect 20 g more plasma, and 720 g donors received around 12 mL more anticoagulant than 700 g donors. Accordingly, Δ citrate concentration was 1.5 times higher (12 µm), with a greater variability observed for 720 g donations. Citrate concentration in the plasma unit was lower in the 720 g group, although not significantly. Comparing outcomes between women and men donating 700 g, we observed higher (and highly variable) Δ citrate and reinfused ACD-A in women, accompanied by lower anticoagulant levels in the unit. Increased Δ citrate is inversely associated with HCT and age in men and with HCT and triglycerides in women. Reinfused ACD-A correlates with HCT in women but not in men. Conclusion: Unit weight setting and sex influence an ACD-A shift from the estimated values toward an increased reinfusion to donor. In parallel, we observed an impact of age and sex on post-donation citrate metabolism. Altogether, these elements should be taken into account for the development of tailored approaches aimed at maintaining similar safety profiles for all donors using different plasmapheresis settings.

A cohort study on the biochemical and haematological parameters of Italian blood donors as possible risk factors of COVID-19 infection and severe disease in the pre- and post-Omicron period.

To investigate the association between biochemical and blood parameters collected before the pandemic in a large cohort of Italian blood donors with the risk of infection and severe disease. We also focused on the differences between the pre- and post-Omicron spread in Italy (i.e., pre- and post-January 01, 2022) on the observed associations. We conducted an observational cohort study on 13750 blood donors was conducted using data archived up to 5 years before the pandemic. A t-test or chi-squared test was used to compare differences between groups. Hazard ratios with 95% confidence intervals for SARS-CoV-2 infection and severe disease were estimated using Cox proportional hazards models. Subgroup analyses stratified by sex, age and epidemic phase of first infection (pre- and post-Omicron spread) were examined. We confirmed a protective effect of groups B and O, while groups A and AB had a higher likelihood of infection and severe disease. However, these associations were only significant in the pre-Omicron period. We found an opposite behavior after Omicron spread, with the O phenotype having a higher probability of infection. When stratified by variant, A antigen appeared to protect against Omicron infection, whereas it was associated with an increased risk of infection by earlier variants. We were able to stratify for the SARS CoV-2 dominant variant, which revealed a causal association between blood group and probability of infection, as evidenced by the strong effect modification observed between the pre- and post-Omicron spread. The mechanism by which group A acts on the probability of infection should consider this strong effect modification.

COVID-19 incidence in women of reproductive age: a population-based study in Reggio Emilia, northern Italy.

BACKGROUND: Despite being at higher risk of severe disease and pregnancy complications, evidence on susceptibility to SARS-CoV-2 infection in pregnancy is still limited. The aim of the study is to compare the likelihood of undergoing a SARS-CoV-2 test and testing positive for COVID-19 in pregnancy and puerperium with that of the general female population of reproductive age. METHODS: This is a retrospective population-based cohort study including 117,606 women of reproductive age (March 2020-September 2021) with 6608 (5.6%) women having ≥ 1 pregnancy. Women were linked to the pregnancy registry to be classified as "non-pregnant", "pregnant", and "puerperium"; then, according to the national case-based integrated COVID-19 surveillance system, all women undergoing a SARS-CoV-2 test during the study period were identified. The Incidence Rate Ratio was calculated to compare the likelihood of being tested for SARS-CoV-2 in pregnant, puerperium and non-pregnant women among all women included. The likelihood of having a COVID-19 diagnosis was calculated using two comparators (not-pregnant women and the person-time before/after pregnancy) by means of Cox proportional hazards models, adjusting for age and with the cluster option to control standard error calculation in repeated pregnancies. Only first infection and swabs before the first one positive were included. RESULTS: The probability of being tested for SARS-CoV-2 was 4.9 (95% CI: 4.8-5.1) and 3.6 times higher (95%CI: 3.4-3.9) in pregnancy (including spontaneous miscarriages) and in the puerperium, respectively. The Hazard Ratio (HR) of covid-19 diagnosis during pregnancy vs. non-pregnancy was 1.17 (95% CI 1.03-1.33) with similar results when comparing the risk during pregnancy with that of the same women outside pregnancy (puerperium excluded), with an HR of 1.13 (95% CI 0.96-1.33); the excess decreased when excluding the test performed at admission for delivery (HR 1.08 (95%CI 0.90-1.30). In the puerperium, the HR was 0.62 (95% CI 0.41-0.92) comparing women with ≥ 1childbirth with all other women and excluding the first two weeks of puerperium. CONCLUSIONS: Women during pregnancy showed a small increase in the risk of infection, compatible with a higher likelihood of being tested. A lower probability of infection during the puerperium was observed during the entire pandemic period, suggesting likely protective behaviors which were effective in reducing their probability of infection.

Determinants of survival in patients with chronic heart failure: a population-based study in Reggio Emilia, Italy.

AIMS: We aim to monitor and improve the quality of the heart failure (HF) integrated assistance model defined by national and regional guidelines and implemented in the province of Reggio Emilia, Italy. Specific aims of the audit were to estimate the prevalence of HF, describe the characteristics of patients with HF and the rate of patients enrolled in the integrated care treated in primary care, and identify socioeconomic and geographic determinants of the 4-year survival of these patients. METHODS AND RESULTS: Retrospective analysis of a cohort of prevalent cases of HF, diagnosed before 31 December 2015 in Reggio Emilia, Italy, alive on 1 January 2016, and residing at the time of diagnosis on the provincial territory. Age and sex-adjusted prevalence of HF by area of residence were calculated according to the standard European population 2013. Patients were followed until death or 31 December 2019, whatever came first. The outcome measure of the study was four-year case fatality. Cox proportional hazards models, adjusted for age, sex, and duration of disease were used to determine the association between socio-geographic factors and death. The 4-year case-fatality rate was 36.7%, and it was the highest in the mountains (50.8%) compared with hills (34.6%), lowland (35.4%) and city (37.7%). The prevalence of HF was the lowest in the mountain [149.9, 95% confidence interval (CI) 112.1-187.7] and the highest in the lowland (340.8, 95% CI 308.7-372.9) and city (308, 95% CI 276.0-321.2). Patients living in the mountains had a lower deprivation index, and fewer hospitalizations prior to official diagnosis, although these characteristics were not statistically significant determinants of HF death in multivariate analysis. Behavioural (smoking and obesity) and socio-geographic characteristics (educational level, deprivation index and area of residence) were not significantly associated with mortality in both univariable and multivariable analysis; however, patients who live in mountains (hazard ratio 1.10, 95% CI 0.73-1.66) or hills (hazard ratio 1.11, 95% CI 0.90-1.37) had a slightly higher risk of death than those living in the city. Only 197 (12.1%) of patients in the cohort were enrolled in the integrated care pathway over the course of 4 years. CONCLUSIONS: Although clinical determinants outweigh the geographic and behavioural disparities in the survival of patients with CHF treated in primary care, effective prevention strategies are needed to address environmental and socio-geographic inequalities in access to primary care and to hasten equitable linkage to integrated care.

SARS-CoV-2 Infection, Vaccination and Risk of Death in People with An Oncological Disease in Northeast Italy.

People with a history of cancer have a higher risk of death when infected with SARS-CoV-2. COVID-19 vaccines in cancer patients proved safe and effective, even if efficacy may be lower than in the general population. In this population-based study, we compare the risk of dying of cancer patients diagnosed with COVID-19 in 2021, vaccinated or non-vaccinated against SARS-CoV-2 and residing in Friuli Venezia Giulia or in the province of Reggio Emilia. An amount of 800 deaths occurred among 6583 patients; the risk of death was more than three times higher among unvaccinated compared to vaccinated ones [HR 3.4; 95% CI 2.9-4.1]. The excess risk of death was stronger in those aged 70-79 years [HR 4.6; 95% CI 3.2-6.8], in patients with diagnosis made <1 year [HR 8.5; 95% CI 7.3-10.5] and in all cancer sites, including hematological malignancies. The study results indicate that vaccination against SARS-CoV-2 infection is a necessary tool to be included in the complex of oncological therapies aimed at reducing the risk of death.

SARS-CoV-2 transmission patterns in educational settings during the Alpha wave in Reggio-Emilia, Italy.

Different monitoring and control policies have been implemented in schools to minimize the spread of SARS-CoV-2. Transmission in schools has been hard to quantify due to the large proportion of asymptomatic carriers in young individuals. We applied a Bayesian approach to reconstruct the transmission chains between 284 SARS-CoV-2 infections ascertained during 87 school outbreak investigations conducted between March and April 2021 in Italy. Under the policy of reactive quarantines, we found that 42.5% (95%CrI: 29.5-54.3%) of infections among school attendees were caused by school contacts. The mean number of secondary cases infected at school by a positive individual during in-person education was estimated to be 0.33 (95%CrI: 0.23-0.43), with marked heterogeneity across individuals. Specifically, we estimated that only 26.0% (95%CrI: 17.6-34.1%) of students and school personnel who tested positive during in-person education caused at least one secondary infection at school. Positive individuals who attended school for at least 6 days before being isolated or quarantined infected on average 0.49 (95%CrI: 0.14-0.83) secondary cases. Our findings provide quantitative insights on the contribution of school transmission to the spread of SARS-CoV-2 in young individuals. Identifying positive cases within 5 days after exposure to their infector could reduce onward transmission at school by at least 30%.

Prevalence and distribution of vascular calcifications at CT scan in patients with and without large vessel vasculitis: a matched cross-sectional study.

OBJECTIVES: The aim of this study was to compare the prevalence, entity and local distribution of arterial wall calcifications evaluated on CT scans in patients with large vessel vasculitis (LVV) and patients with lymphoma as reference for the population without LVV. METHODS: All consecutive patients diagnosed with LVVs with available baseline positron emission tomography-CT (PET-CT) scan performed between 2007 and 2019 were included; non-LVV patients were lymphoma patients matched by age (±5 years), sex and year of baseline PET-CT (≤2013; >2013). CT images derived from baseline PET-CT scans of both patient groups were retrospectively reviewed by a single radiologist who, after setting a threshold of minimum 130 Hounsfield units, semiautomatically computed vascular calcifications in three separate locations (coronaries, thoracic and abdominal arteries), quantified as Agatston and volume scores. RESULTS: A total of 266 patients were included. Abdominal artery calcifications were equally distributed (mean volume 3220 in LVVs and 2712 in lymphomas). Being in the LVVs group was associated with the presence of thoracic calcifications after adjusting by age and year of diagnosis (OR 4.13, 95% CI 1.35 to 12.66; p=0.013). Similarly, LVVs group was significantly associated with the volume score in the thoracic arteries (p=0.048). In patients >50 years old, calcifications in the coronaries were more extended in non-LVV patients (p=0.027 for volume). CONCLUSION: When compared with patients without LVVs, LVVs patients have higher calcifications in the thoracic arteries, but not in coronary and abdominal arteries.

High temperature, COVID-19, and mortality excess in the 2022 summer: a cohort study on data from Italian surveillances.

We aimed to assess whether the effect of high temperature on mortality differed in COVID-19 survivors and naive. We used data from the summer mortality and COVID-19 surveillances. We found 3.8 % excess risk in 2022 summer, compared to 2015-2019, while 20 % in the last fortnight of July, the period with the highest temperature. The increase in mortality rates during the second fortnight of July was higher among naïve compared to COVID-19 survivors. The time series analysis confirmed the association between temperatures and mortality in naïve people, showing an 8 % excess (95%CI 2 to 13) for a one-degree increase of Thom Discomfort Index while in COVID-19 survivors the effect was almost null with -1 % (95%CI -9 to 9). Our results suggest that the high fatality rate of COVID-19 in fragile people has decreased the proportion of susceptible people who can be affected by the extremely high temperature.

Risk of SARS-CoV-2 reinfection by vaccination status, predominant variant and time from prior infection: a cohort study, Reggio Emilia province, Italy, February 2020 to February 2022.

BackgroundUnderstanding the epidemiology of reinfections is crucial for SARS-CoV-2 control over a long period.AimTo evaluate the risk of SARS-CoV-2 reinfection by vaccination status, predominant variant and time after first infection.MethodsWe conducted a cohort study including all residents in the Reggio Emilia province on 31 December 2019, followed up until 28 February 2022 for SARS-CoV-2 first infection and reinfection after 90 days. Cox models were used to compare risk of first infection vs reinfection, adjusting for age, sex, vaccine doses and comorbidities.ResultsThe cohort included 538,516 residents, 121,154 with first SARS-CoV-2 infections and 3,739 reinfections, most in the Omicron BA.1 period. In the pre-Omicron period, three doses of vaccine reduced risk of reinfection by 89% (95% CI: 87-90), prior infection reduced risk by 90% (95% CI: 88-91), while two doses and infection reduced risk by 98% (95% CI: 96-99). In the Omicron BA.1 period, protection estimates were 53% (95% CI: 52-55), 9% (95% CI: 4-14) and 76% (95% CI: 74-77). Before Omicron, protection from reinfection remained above 80% for up to 15 months; with Omicron BA.1, protection decreased from 71% (95% CI: 65-76) at 5 months to 21% (95% CI: 10-30) at 22 months from the first infection. Omicron BA.1 reinfections showed 48% (95% CI: 10-57) lower risk of severe disease than first infections.ConclusionsNatural immunity acquired with previous variants showed low protection against Omicron BA.1. Combined vaccination and natural immunity seems to be more protective against reinfection than either alone. Vaccination of people with prior infection reduced the risk of severe disease.

Takayasu arteritis and large-vessel giant cell arteritis in Italian population. Comprehensive analysis from a single institutional cohort of 184 cases.

OBJECTIVE: To compare clinical and imaging characteristics in patients with Takayasu arteritis (TAK) and large vessel-giant cell arteritis (LV-GCA) in an Italian population. METHODS: We conducted a retrospective monocenter study comparing characteristics and outcomes of a cohort of 59 patients with TAK and a cohort of 127 patients with LV-GCA diagnosed between 1996 and 2016. Most of them (92%) were followed up for at least 24 months at Reggio Emilia Hospital (Italy). We also reviewed the literature discussing the results of the published manuscripts comparing LV-GCA to TAK RESULTS: LV-GCA patients had a higher prevalence of males (p = 0.003), and more frequently presented with cranial symptoms (p = 0.001), fever ≥38 °C (p = 0.007), polymyalgia rheumatica (p = 0.001), and hypertension (p = 0.001), and they had higher ESR levels at diagnosis (p = 0.0001). Differently, TAK patients had longer delay to diagnosis from the beginning of symptoms (p = 0.048), they presented more frequently with loss of pulses of large arteries (p = 0.0001), vascular bruits (p = 0.001), limb claudication (p = 0.003), myocardial infarction/angina (p = 0.03), and hypertension induced by renal artery stenosis (p = 0.001). Regarding treatment, TAK patients received a higher total and at 1 year cumulative prednisone doses (p = 0.0001 and p = 0.001, respectively), they had a longer duration of prednisone therapy (p = 0.008), and received during follow-up more frequently traditional immunosuppressants (p = 0.0001) and biological agents (p = 0.0001). Flares were more frequently observed in TAK patient (p = 0.001), while no differences were observed for long-term remission. New vascular procedures during the follow-up were more frequently performed in TAK patients (p = 0.0001). Regarding imaging at diagnosis, TAK patients had more frequently vascular stenosis/occlusion (p = 0.0001) and a higher number of vessels with structural damage per person (p = 0.0001), while LV-GCA patients had a higher number of inflamed vessels per person (p = 0.0001). Comparing the involved vascular districts at diagnosis for the presence of vessel inflammation and/or arterial damage, patients with LV-GCA had a more frequent involvement of thoracic and abdominal aorta (p = 0.024 and p = 0.007, respectively), and axillary, iliac and femoral arteries (p = 0.018, p = 0.002, and p = 0.0001. respectively), while in TAK patients, brachiocephalic, celiac, mesenteric and renal arteries were more frequently involved (p = 0.011, p = 0.019, p = 0.019, and p = 0.005, respectively). At imaging arterial damage at diagnosis was more frequently observed in TAK patients, specifically at common carotid, brachiocephalic, and subclavian arteries (p = 0.0001, p = 0.006, p = 0.0001, respectively) and descending aorta (p = 0.022). Regarding imaging during the follow-up, TAK patients developed more frequently new vascular stenosis/occlusion (p = 0.0001) and new vascular thickening (p = 0.002), no differences were observed for the development of new dilatation/aneurysm between the two vasculitides. CONCLUSION: Patients with TAK and LV-GCA show a number of similarities and also differences. Indeed, it is unclear whether they are part of the same disease spectrum or they are different conditions. As more information regarding the pathogenesis and etiology becomes known, answers to these questions are like to be forthcoming.

Estimation of the incubation period and generation time of SARS-CoV-2 Alpha and Delta variants from contact tracing data.

Quantitative information on epidemiological quantities such as the incubation period and generation time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is scarce. We analysed a dataset collected during contact tracing activities in the province of Reggio Emilia, Italy, throughout 2021. We determined the distributions of the incubation period for the Alpha and Delta variants using information on negative polymerase chain reaction tests and the date of last exposure from 282 symptomatic cases. We estimated the distributions of the intrinsic generation time using a Bayesian inference approach applied to 9724 SARS-CoV-2 cases clustered in 3545 households where at least one secondary case was recorded. We estimated a mean incubation period of 4.9 days (95% credible intervals, CrI, 4.4-5.4) for Alpha and 4.5 days (95% CrI 4.0-5.0) for Delta. The intrinsic generation time was estimated to have a mean of 7.12 days (95% CrI 6.27-8.44) for Alpha and of 6.52 days (95% CrI 5.54-8.43) for Delta. The household serial interval was 2.43 days (95% CrI 2.29-2.58) for Alpha and 2.74 days (95% CrI 2.62-2.88) for Delta, and the estimated proportion of pre-symptomatic transmission was 48-51% for both variants. These results indicate limited differences in the incubation period and intrinsic generation time of SARS-CoV-2 variants Alpha and Delta compared to ancestral lineages.

The epidemiology of oral cancer during the COVID-19 pandemic in Northern Italy: Incidence, survival, prevalence.

Despite novel treatment approaches, oral cancer survival has not improved significantly and the disease often presents a disabling path for patients. The aim of this work was to describe the epidemiological data of oral cancers in a province of northern Italy. Incident cases in the period 1996-2020 and EU population standardized rates were reported for Oral Cavity cancer (OC) and OroPharyngeal cancer (OP). Annual percent changes (APC) were estimated with joint point analysis. The 5-year survival was calculated in three different periods: 1996-2000, 2001-2010 and 2011-2015. From 1996 to 2020, 771 cases of oral cancers (442 OC and 329 OP) were recorded with the age-standardized incidence rate 7.28 (10.74 in males and 3.97 in females): 3.82 for OC and 3.47 for OP. In males there is a significant increase in the incidence of OP up to 2017 (APC 11; 95% CI, 4.9-17.5), which then decreases; in females the rates are constant. In 2020 (the era of Covid-19), we did not see a decline in incidence compared to 2019. The 5-year survival (for cases diagnosed in 2011-2015) was 55.6%, 56.5% and 56% for OC, OP and OC + OP, respectively; it was somewhat higher in females and was undergoing some changes over the course of years. The number of prevalent cases as of 1 January 2021 is 314 (175 OC, 139 OP). The study showed a decline in cancers in men, particularly for OP; survival shows improvement in the long-term examined; Covid-19 had no negative impact on 2020 diagnoses.

Incidence and Characteristics of Adverse Events after COVID-19 Vaccination in a Population-Based Programme.

Compliance with vaccination is linked to its safety. In Italy, a plan to identify people who could be at an increased risk of adverse events (AEs) was defined so they could be vaccinated in a protected setting. We conducted an audit to describe the process of AE risk assessment and occurrence in the Reggio Emilia Province in Italy in people who received any of the four COVID-19 vaccines currently used in Italy. Incidence of AEs was calculated by dose and type of vaccine and type of setting (standard vs. protected). After 182,056 first doses were administered, 521 (0.3%) AEs were reported. Most of the AEs were non-serious (91.4%) and non-allergic (92.7%). The percentage of AEs was similar in both settings: 0.3% in the standard setting and 0.2% in the protected setting. However, the incidence of AEs was higher among those who had an allergist visit than among those who did not (IR 666.7 vs. 124.9). All deaths (1.6/100.000) occurred in standard settings and after the Pfizer and Moderna vaccines. The incidence of AEs was lower after the second dose (IR 286.2 vs. 190.3), except for mRNA vaccines, for which it was higher after the second dose (IR 169.8 vs. 251.8). Although vaccination in a protected medical setting could reassure patients with a history of allergies to be vaccinated, allergy history and other anamnestic information is not useful in predicting the risk of COVID-19 vaccine-related AEs in the general population.

Intrinsic generation time of the SARS-CoV-2 Omicron variant: An observational study of household transmission.

Background: Starting from the final months of 2021, the SARS-CoV-2 Omicron variant expanded globally, swiftly replacing Delta, the variant that was dominant at the time. Many uncertainties remain about the epidemiology of Omicron; here, we aim to estimate its generation time. Methods: We used a Bayesian approach to analyze 23,122 SARS-CoV-2 infected individuals clustered in 8903 households as determined from contact tracing operations in Reggio Emilia, Italy, throughout January 2022. We estimated the distribution of the intrinsic generation time (the time between the infection dates of an infector and its secondary cases in a fully susceptible population), realized household generation time, realized serial interval (time between symptom onset of an infector and its secondary cases), and contribution of pre-symptomatic transmission. Findings: We estimated a mean intrinsic generation time of 6.84 days (95% credible intervals, CrI, 5.72-8.60), and a mean realized household generation time of 3.59 days (95%CrI: 3.55-3.60). The household serial interval was 2.38 days (95%CrI 2.30-2.47) with about 51% (95%CrI 45-56%) of infections caused by symptomatic individuals being generated before symptom onset. Interpretation: These results indicate that the intrinsic generation time of the SARS-CoV-2 Omicron variant might not have shortened as compared to previous estimates on ancestral lineages, Alpha and Delta, in the same geographic setting. Like for previous lineages, pre-symptomatic transmission appears to play a key role for Omicron transmission. Estimates in this study may be useful to design quarantine, isolation and contact tracing protocols and to support surveillance (e.g., for the accurate computation of reproduction numbers). Funding: The study was partially funded by EU grant 874850 MOOD.

A deep learning approach for Spatio-Temporal forecasting of new cases and new hospital admissions of COVID-19 spread in Reggio Emilia, Northern Italy.

BACKGROUND: Since February 2020, the COVID-19 epidemic has rapidly spread throughout Italy. Some studies showed an association of environmental factors, such as PM10, PM2.5, NO2, temperature, relative humidity, wind speed, solar radiation and mobility with the spread of the epidemic. In this work, we aimed to predict via Deep Learning the real-time transmission of SARS-CoV-2 in the province of Reggio Emilia, Northern Italy, in a grid with a small resolution (12 km × 12 km), including satellite information. METHODS: We focused on the Province of Reggio Emilia, which was severely hit by the first wave of the epidemic. The outcomes included new SARS-CoV-2 infections and COVID-19 hospital admissions. Pollution, meteorological and mobility data were analyzed. The spatial simulation domain included the Province of Reggio Emilia in a grid of 40 cells of (12 km)2. We implemented a ConvLSTM, which is a spatio-temporal deep learning approach, to perform a 7-day moving average to forecast the 7th day after. We used as training and validation set the new daily infections and hospital admissions from August 2020 to March 2021. Finally, we assessed the models in terms of Mean Absolute Error (MAE) compared with Mean Observed Value (MOV) and Root Mean Squared Error (RMSE) on data from April to September 2021. We tested the performance of different combinations of input variables to find the best forecast model. FINDINGS: Daily new cases of infection, mobility and wind speed resulted in being strongly predictive of new COVID-19 hospital admissions (MAE = 2.72 in the Province of Reggio Emilia; MAE = 0.62 in Reggio Emilia city), whereas daily new cases, mobility, solar radiation and PM2.5 turned out to be the best predictors to forecast new infections, with appropriate time lags. INTERPRETATION: ConvLSTM achieved good performances in forecasting new SARS-CoV-2 infections and new COVID-19 hospital admissions. The spatio-temporal representation allows borrowing strength from data neighboring to forecast at the level of the square cell (12 km)2, getting accurate predictions also at the county level, which is paramount to help optimise the real-time allocation of health care resources during an epidemic emergency.