Elexacaftor-tezacaftor-ivacaftor (ETI), a triple CFTR modulator combination, has proven to be highly effective in patients with cystic fibrosis (CF) carrying at least one Phe508del mutation. Since October 2022 triple therapy has been approved in Italy for 6 to 11-year-old children with this genotype. We report preliminary data on efficacy and safety of ETI in that patient population after one month of treatment.

The triple-combination of ETI has been associated to significant improvement in lung function and rate of pulmonary exacerbations (Middleton, NEJM 2019). Conventional MRI has been proposed as a radiation-free imaging modality to investigate functional and morphological lung changes over the course of the disease (Pennati, JMRI 2021). The study aims to evaluate changes in MRI-ventilation measures in patients with CF lung disease treated with ETI. We performed a longitudinal retrospective study on 7 consecutive patients with severe CF lung disease (25±4 years, FEV1 40±9%), over 1-year treatment with ETI. MRI was available at months 0 and 12 in 5 patients. End-inspiration (INSP) and end-expiration (EXP) images were registered to estimate Δ1H-MRI (EXP-INSP) as a measure of regional ventilation. We defined low ventilation volume (%LVV) as the percent volume with Δ1H-MRI<5%. From month 0 to 12, FEV1 and FEF25-75 increased by 45% and 65% (p=0.01). Lung clearance index decreased by 45%. Δ1H-MRI increased by 45%(p=0.01) and %LVV decreased by 12% (p=0.19) (Fig.1). MRI-ventilation measures improved in patients treated with ETI. Preliminary results suggest that MRI may provide a sensitive tool for the evaluation of CF lung disease under treatment with no radiation exposure. Supported by Italian Cystic Fibrosis Research Foundation (Grant FFC#21/2020)

The principal aim of this review is to present the current knowledge regarding acute otitis media (AOM) with spontaneous tympanic membrane perforation (STMP) and to address the question of whether AOM with STMP is a disease with specific characteristics or a severe case of AOM. PubMed was used to search for all studies published over the past 15 years using the key words “acute otitis media” and “othorrea” or “spontaneous tympanic membrane perforation”. More than 250 articles were found, but only those published in English and providing data on aspects related to perforation of infectious origin were considered. Early Streptococcus pneumoniae infection due to invasive pneumococcal strains, in addition to coinfections and biofilm production due mainly to non-typeable Haemophilus influenzae, seem to be precursors of STMP. However, it is unclear why some children have several STMP episodes during the first years of life that resolve without complications in adulthood, whereas other children develop chronic suppurative otitis media. Although specific aetiological agents appear to be associated with an increased risk of AOM with STMP, further studies are needed to determine whether AOM with STMP is a distinct disease with specific aetiological, clinical and prognostic characteristics or a more severe case of AOM than the cases that occur without STMP. Finally, it is important to identify preventive methods that are useful not only in otitis-prone children with uncomplicated AOM, but also in children with recurrent AOM and those who experience several episodes with STMP.