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Italy initiated elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (pwCF) in July 2021. It has led to dramatic improvements in lung function, BMI, sweat chloride, and respiratory symptoms. However, few data are available on side effects or effects on a broad range of outcomes. How does ETI affect mental health, cognitive processing, neuropsychological side effects, GI symptoms, and health-related quality of life over time? This was a prospective, "real-world" longitudinal study. Participants were recruited consecutively and evaluated at initiation (T0) and after 1 month, 3 months, and 6 months of starting treatment. Assessments included depression (nine-item Patient Health Questionnaire), anxiety (seven-item Generalized Anxiety Disorder), cognition (Symbol Digit Modalities Test), GI Symptom Tracker, and health-related quality of life (Cystic Fibrosis Questionnaire-Revised). Based on literature, an ad hoc questionnaire was developed to assess side effects: insomnia, headache, memory problems, "brain fog," and concentration problems. Following descriptive analyses, longitudinal data were analyzed by using mixed models for repeated measures, controlling for age and sex when appropriate. Ninety-two consecutive pwCF (female/male, 46/46; mean age, 25.4 years) participated. FEV 1 increased initially and then remained stable. BMI also increased significantly from T0 to 6 months (P <.01). Depression improved from T0 to 1 month (P <.001); however, no changes in anxiety were found. Cognitive processing improved from T0 to subsequent assessments. Positive changes were reported on the GI Symptom Tracker for stools and adherence challenges, although no changes were found for abdominal pain and digestion. Side effects occurred in 10% to 29%, with no reduction over time; insomnia increased significantly across time. Female participants reported more side effects than male participants (ie, insomnia, headache, concentration problems, brain fog). This prospective study evaluated the effects of ETI using multiple measures. Significant improvements were found in many domains; however, side effects were reported by a substantial proportion of pwCF, with no improvements over time. Female participants reported more side effects than male participants. pwCF should be followed up systematically to assess the frequency of side effects after starting this new modulator. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is one of the pathogens most involved in health care-associated infections in recent decades. Known for its ability to accumulate several antimicrobial resistance mechanisms, it possesses the oxacillinase blaoxa-23, a carbapenemase now endemic in Italy. Acinetobacter species are not frequently observed in patients with cystic fibrosis, and multidrug-resistant A. baumannii is a rare event in these patients. Non-mucoid A. baumannii carrying the blaoxa-23 gene has been sporadically detected. Here, we describe the methods used to detect blaoxa-23 in the first established case of pulmonary infection via a mucoid strain of A. baumannii producing carbapenemase in a 24-year-old cystic fibrosis patient admitted to Bambino Gesù Children's Hospital in Rome, Italy. This strain, which exhibited an extensively drug-resistant antibiotype, also showed a great ability to further increase its resistance in a short time. [ABSTRACT FROM AUTHOR]

Background: The introduction of the novel therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been effective in improving weight gain in both clinical trials and real-world studies. However, the magnitude of this effect appears to be heterogeneous across patient subgroups. This study aims to identify potential determinants of heterogeneity in weight gain following 6-month ETI therapy. Methods: We conducted a multicenter, prospective cohort study enrolling 92 adults with CF at two major CF centers in Italy with follow-up visit at one month and six months from ETI initiation. The treatment's effect on weight changes was evaluated using mixed effect regression models that included subject-specific random intercepts and fixed effects for potential predictors of treatment response, time and a predictor-by-time interaction term. Results: The mean weight gain at six months from the start of treatment was 4.6 kg (95% CI: 2.3–6.9) for the 10 patients with underweight, 3.2 kg (95% CI: 2.3-4.0) for the 72 patients with normal weight, and 0.7 kg (95% CI: -1.6-3.0) for the 10 patients with overweight. After six months of ETI treatment, 8 (80%) of the patients with underweight transitioned to the normal weight category, while 11 (15.3%) of the normal-weight patients became overweight. The major determinants of heterogeneity in weight gain were the baseline BMI and the presence of at least one CFTR residual function mutation, explaining 13% and 8% of the variability, respectively. Conclusions: Our results indicate that ETI is highly effective in improving weight gain in underweight subjects with CF. However, our data also suggests the need for close monitoring of excess weight gain to prevent potential cardiometabolic complications. Highlights: We reported heterogeneity in weight gain after 6 months of treatment with ETI. Baseline BMI and CFTR genotype predict heterogeneity in treatment response. People with underweight received the greatest benefit from ETI treatment. An amount of 15% of normal-weight subjects became overweight. [ABSTRACT FROM AUTHOR]