Background: Annual vaccination is the most effective way to combat influenza. As influenza viruses evolve, seasonal vaccines are updated annually. Within the European project Development of Robust and Innovative Vaccine Effectiveness (DRIVE), a cohort study involving Italian healthcare workers (HCWs) was carried out during the 2018-2019 season. Two aims were defined: to measure influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza cases and to conduct an awareness-raising campaign to increase vaccination coverage. Methods: Each subject enrolled was followed up from enrollment to the end of the study. Each HCW who developed ILI was swabbed for laboratory confirmation of influenza. Influenza viruses were identified by molecular assays. A Cox regression analysis, crude and adjusted for confounding variables, was performed to estimate the IVE. Results: Among the 4483 HCWs enrolled, vaccination coverage was 32.5%, and 308 ILI cases were collected: 23.4% were positive for influenza (54.2% A(H1N1) pdm09; 45.8% A(H3N2)). No influenza B viruses were detected. No overall IVE was observed. Analyzing the subtypes of influenza A viruses, the IVE was estimated as 45% (95% CI: -59 to 81) for A(H1N1) pdm09. Conclusions: Vaccination coverage among HCWs increased. Study difficulties and the circulation of drifted variants of A(H3N2) could partly explain the observed IVE.

Although meningococcal disease has a low incidence in Italy, it is a public health concern owing to its high lethality rate and high frequency of transitory and/or permanent sequelae among survivors. The highest incidence rates are recorded in infants, children and adolescents, and most of the cases are due to Neisseria meningitidis B. In Italy, anti-meningococcal B (anti-MenB) vaccination is free for infants but, despite the considerable disease burden in adolescents, no national recommendation to vaccinate in this age-group is currently available. The aim of this study was to assess the main available scientific evidence to support the Italian health authorities in implementing a program of free anti-MenB vaccination for adolescents. We conducted an overview of the scientific literature on epidemiology, disease burden, immunogenicity and safety of available vaccines, and economic evaluations of vaccination strategies. Each case of invasive meningococcal disease generates a considerable health burden (lethality rate: 9%; up to 60% of patients experience at least one sequela) in terms of impaired quality of life for survivors and high direct and indirect costs (the mean overall cost of acute phase for a single case amounts to about EUR 13,952; the costs for post-acute and the long-term phases may vary widely depending of the type of sequela, reaching an annual cost of about EUR 100,000 in cases of severe neurological damage). Furthermore, vaccination against meningococcus B in adolescence proved cost-effective. The study highlights the need to actively offer the anti-MenB vaccination during adolescence at a national level. This would make it possible to avoid premature deaths and reduce the high costs borne by the National Health Service and by society of supporting survivors who suffer temporary and/or permanent sequelae.

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Background and Aims Acute kidney injury (AKI) is a major complication in cancer patients receiving immune checkpoint inhibitors (ICIs). Previous studies have not accurately distinguished the various potential underlying causes of AKI due to the limited use of renal biopsy. Here, we reviewed cases of biopsy-proven acute tubulointerstitial nephritis (ATIN) in patients treated with ICIs to describe the clinical and laboratory characteristics and outcomes of this condition. Method We conducted a pooled analysis of clinical cases published up to 1 May 2022. The search terms on PubMed were [(Pembrolizumab OR Nivolumab OR Ipilimumab OR Atezolizumab OR Avelumab OR Durvalumab) AND (Nephritis)]. Only cases with biopsy-proven ATIN were included. Among a total of 111 patients identified, 83 were eligible for this analysis. We added two patients from our Institution. We collected data on clinical characteristics, renal biopsy findings, and laboratory examinations. AKI was graded according to the KDIGO criteria. As outcomes, we considered: complete renal recovery if serum creatinine returned to baseline +0.3 mg/dL, no recovery if patients needed dialysis and partial recovery in other cases. Results Overall, 85 patients (56 male) with an age of 61.4±19 years were evaluated. 43 patients (51%) had melanoma, 25 (30%) non-small cell lung cancer, 8 renal carcinoma, and 9 other cancers. ICI treatment consisted of PD-1, PDL-1 (nivolumab, pembrolizumab, atezolizumab) and CTLA4 inhibitors (i) (ipilimumab) or combination PD-1i-CTLA4i (Table 1). Renal toxicity developed after a median of four cycles of therapy, but in most cases (n = 59) after at least three treatment cycles. Eleven patients (14%) presented with AKI stage 1, 16 patients (20.5%) with stage 2, and 51 patients (65.5%) with AKI stage 3, including five patients requiring dialysis. Among AKI3 patients there was a significantly higher prevalence of patients at the first therapy line (p = 0.04), while all the 19 patients treated with the dual ICI blockade developed AKI3, compared with 29 patients out of the 52 taking a single agent (Figure 1A). Seventy-seven patients received steroids, while 7 patients did not receive any therapy. ICI treatment was withdrawn in 65 out of 69 patients with available data. Following AKI resolution, in 15 patients ICI was restarted, but in six (40%) AKI recurred. Overall, 32 patients (40%) presented a complete renal recovery, 45 patients (56.2%) had a partial recovery, and 3 patients (3.8%) did not recover. Among patients who did not fully recover, there was a higher prevalence of those treated with dual ICI blockade and presenting with AKI stage 3 (Figure 1B). At logistic regression, complete renal recovery was inversely associated with dual ICI blockade (OR 0.1, 95CI 0.02-0.5, p = 0.006) and AKI 3 (OR 0.31, 95CI 0.1-0.9, p = 0.04), but only the association with dual ICI therapy remained significant at multivariate analysis. Conclusion ICI-related ATIN may develop late after the initiation of therapy. It may present as a severe form of AKI, particularly in patients with dual ICI blockade. Although this complication may be partially reversible, concerns remain about the renal function sequelae and the possibility of restarting treatment after AKI resolution due to the risk of recurrence.

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