Height Velocity in Pediatric Cystic Fibrosis Under Triple CFTR Modulator Therapy: A Real-Life Monocentric Experience.

Cystic fibrosis (CF) is a multi-system disorder characterized by chronic respiratory failure, malnutrition, and impaired growth. Achieving linear growth above the 50th percentile is associated with better pulmonary outcomes. Since October 2022, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved in Italy for children aged ≥6 years.

Development and Validation of a New LC-MS/MS Method for Simultaneous Quantification of Ivacaftor, Tezacaftor and Elexacaftor Plasma Levels in Pediatric Cystic Fibrosis Patients.

: "CFTR modulators" (also named "caftor") have been developed and introduced into clinical practice to improve the functionality of defective CFTR protein. Therapeutic drug monitoring (TDM) is not currently used for CFTR modulators in routine clinical practice and there is still much to learn about the pharmacokinetic/pharmacodynamic (PK/PD) and the safety profiles of these drugs in a real-world setting. Moreover, therapeutic ranges are not yet available for both pediatric and adult cystic fibrosis (CF) patients.

Elexacaftor/tezacaftor/ivacaftor efficacy in intestinal organoids with rare CFTR variants in comparison to CFTR-F508del and CFTR-wild type controls.

Cystic fibrosis is a life-shortening genetic disease caused by pathological variants of the cystic fibrosis transmembrane conductance regulator gene. The CFTR modulator therapy elexacaftor, tezacaftor and ivacaftor (ETI) rescues CFTR protein function and has made a significant impact on the lives of many people with CF. In Europe, ETI is currently available for people with CF who have at least one F508del mutation whilst the effect of ETI on rare CFTR variants remains unknown, albeit that many of such variants may be restored through ETI.

Use of Lung Ultrasound in Cystic Fibrosis: Is It a Valuable Tool?

Cystic fibrosis (CF) is a multisystem disorder characterized by progressive respiratory deterioration, significantly impacting both quality of life and survival. Over the years, lung ultrasound (LUS) has emerged as a promising tool in pediatric respiratory due to its safety profile and ease at the bedside. In the era of highly effective CF modulator therapies and improved life expectancy, the use of non-ionizing radiation techniques could become an integral part of CF management, particularly in the pediatric population.

Year in review 2023 - Back to the future.

This review synthesizes articles published in 2023, focusing on the impact of elexacaftor-tezacaftor-ivacaftor (ETI) in cystic fibrosis (CF) care. Real-world data highlights sustained benefits of ETI across age groups, while challenges like neuropsychological side effects persist. Beyond CFTR modulators, research explores telemedicine and novel therapies.

Lung clearance index short-term variability in cystic fibrosis: a pre-post pulmonary exacerbation study.

Background: Multiple Breath washout (MBW) represents an important tool to detect early a possible pulmonary exacerbation especially in Cystic Fibrosis (CF) disease. Lung clearance index (LCI) is the most commonly reported multiple breath washout (MBW) index and in the last years was used as management measure for evaluation. Our aim was to analyze clinical utility of LCI index variability in pulmonary exacerbation in CF after intravenous (IV) antibiotic therapy.

Longitudinal Effects of Elexacaftor/Tezacaftor/Ivacaftor: Multidimensional Assessment of Neuropsychological Side Effects and Physical and Mental Health Outcomes in Adolescents and Adults.

Background: 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.

Identification of the Gene in the First Mucoid XDR Isolated from a Patient with Cystic Fibrosis.

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 , a carbapenemase now endemic in Italy. species are not frequently observed in patients with cystic fibrosis, and multidrug-resistant is a rare event in these patients.

Heterogeneity of weight gain after initiation of Elexacaftor/Tezacaftor/Ivacaftor in people with cystic fibrosis.

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.

Theratyping of the Rare CFTR Variants E193K and R334W in Rectal Organoid-Derived Epithelial Monolayers.

Background: The effect of presently available CFTR modulator combinations, such as elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), on rare CFTR alleles is often unknown. Several assays have been developed, such as forskolin-induced swelling (FIS), to evaluate the rescue of such uncommon CFTR alleles both by established and novel modulators in patient-derived primary cell cultures (organoids). Presently, we assessed the CFTR-mediated electrical current across rectal organoid-derived epithelial monolayers.

Lung ultrasound in bronchiolitis.

Background: Bronchiolitis is the most common acute viral infection of the lower respiratory tract in infants. Clinical severity is associated with different risk factors; however, no clinical, laboratory, or radiological findings are able to predict the course of the disease in full-term infants. Lung ultrasound (LUS) is a valid technique for the diagnosis and evaluation of pediatric respiratory diseases.

Differences and similarities between SARS-CoV and SARS-CoV-2: spike receptor-binding domain recognition and host cell infection with support of cellular serine proteases.

Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic by the end of March 2020. In contrast to the 2002-2003 SARS-CoV outbreak, which had a higher pathogenicity and lead to higher mortality rates, SARSCoV-2 infection appears to be much more contagious. Moreover, many SARS-CoV-2 infected patients are reported to develop low-titer neutralizing antibody and usually suffer prolonged illness, suggesting a more effective SARS-CoV-2 immune surveillance evasion than SARS-CoV.

Covid-19 in children: A brief overview after three months experience.

Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults.

What do differences in case fatality ratios between children and adults tell us about COVID-19?

https://bit.ly/36BzTaD

Will children reveal their secret? The coronavirus dilemma.

https://bit.ly/35ZLf7V

A single centre study of viral community-acquired pneumonia in children: No evidence of SARS-CoV-2 from October 2019 to March 2020.

Pneumonia is an important cause of morbidity and mortality in children. We described viral aetiologies, with particular interest in detecting SARS-CoV-2, in hospitalized pneumonia children. Human rhinovirus was the most frequently detected agent.

Will children reveal their secret? The coronavirus dilemma.

Epidemiological evidences show that SARS-CoV-2 infection in children is less frequent and severe than adults. Age-related ACE2 receptor expression, lymphocyte count and trained immunity might be the keystone to reveal children's secret.