Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

On the alleged origin of geminiviruses from extrachromosomal DNAs of phytoplasmas

<p>Abstract</p> <p>Background</p> <p>Several phytoplasmas, wall-less phloem limited plant pathogenic bacteria, have been shown to contain extrachromosomal DNA (EcDNA) molecules encoding a replication associated protein (Rep) similar to that of geminiviruses, a major group of single stranded (ss) DNA plant viruses. On the basis of that observation and of structural similarities between the capsid proteins of geminiviruses and the <it>Satellite tobacco necrosis virus</it>, it has been recently proposed that geminiviruses evolved from phytoplasmal EcDNAs by acquiring a capsid protein coding gene from a co-invading plant RNA virus.</p> <p>Results</p> <p>Here we show that this hypothesis has to be rejected because (i) the EcDNA encoded Rep is not of phytoplasmal origin but has been acquired by phytoplasmas through horizontal transfer from a geminivirus or its ancestor; and (ii) the evolution of geminivirus capsid protein in land plants implies missing links, while the analysis of metagenomic data suggests an alternative scenario implying a more ancient evolution in marine environments.</p> <p>Conclusion</p> <p>The hypothesis of geminiviruses evolving in plants from DNA molecules of phytoplasma origin contrasts with other findings. An alternative scenario concerning the origin and spread of Rep coding phytoplasmal EcDNA is presented and its implications on the epidemiology of phytoplasmas are discussed.</p