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.

Deleterious effect of on F508del-CFTR rescued by elexacaftor/tezacaftor/ivacaftor is clinical strain-dependent in patient-derived nasal cells.

Background: The triple cystic fibrosis transmembrane conductance regulator (CFTR) modulators combination elexacaftor/tezacaftor/ivacaftor (ETI) has been approved for people with cystic fibrosis (pwCF) bearing at least one allele. Despite the development of CFTR modulators having dramatically improved respiratory outcomes in pwCF, clinical studies have showed variable responses to this drug formulation. Of note, airway inflammation and bacterial colonisation persist in the upper and lower respiratory tract even in ETI-treated patients.

IL-17 family members exert an autocrine pro-inflammatory loop in CF respiratory epithelial cells ex vivo.

Background: Lungs of people with Cystic Fibrosis (pwCF) are characterized by chronic inflammation and infection with P. aeruginosa. High levels of IL-17 A and F have been observed in sputum of pwCF and the interleukin-17(IL-17) family (A-to-F) has been suggested to play a key role in CF pulmonary disease.

The Challenging Life of Mutators: How Survives between Persistence and Evolution in Cystic Fibrosis Lung.

Cystic fibrosis (CF) is a life-threatening genetic disease characterised by chronic lung infections sustained by opportunistic pathogens such as During the chronic long-lasting lung infections, adapts to the host environment. Hypermutability, mainly due to defects in the DNA repair system, resulting in an increased spontaneous mutation rate, represents a way to boost the rapid adaptation frequently encountered in CF isolates. We selected 609 isolates from 51 patients with CF chronically colonised by to study, by full-length genome sequencing, the longitudinal evolution of the bacterium.

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.

An inflammatory Signature of Glucose Impairment in Cystic Fibrosis.

Objective And Design: Cystic fibrosis-related diabetes (CFRD) is a severe complication associated with increased morbidity and mortality in cystic fibrosis (CF) patients. Extensive inflammatory state in CF leads to pancreas damage and insulin resistance with consequent altered glucose tolerance and CFRD development. The aim of the present study was to identify circulating levels of inflammatory markers specifically associated with impaired glucose tolerance (IGT) and overt CFRD in a sample of young adults with CF.

Environmental Microbial Contamination during Cystic Fibrosis Group-Based Psychotherapy.

Living with cystic fibrosis (CF) exposes patients to the risk of developing anxiety and depression, with therapeutic compliance reduction, hospitalization increase, and quality of life and health outcomes deterioration. As pulmonary infections represent the major cause of morbidity and mortality in patients with CF, environmental contamination due to droplet dispersion and the potential transmission from environment to such patients should be prevented. Therefore, in-person contact, including group-based psychotherapy, are strongly discouraged.

A Prospective Study of Hematologic Complications and Long-Term Survival of Italian Patients Affected by Shwachman-Diamond Syndrome.

Objective: To describe the hematologic outcome and long-term survival of patients enrolled in the Shwachman-Diamond syndrome Italian Registry.

Study Design: A retrospective and prospective study of patients recorded in the Shwachman-Diamond syndrome Italian Registry.

Results: The study population included 121 patients, 69 males and 52 females, diagnosed between 1999 and 2018.

Metabolomic Analysis by Nuclear Magnetic Resonance Spectroscopy as a New Approach to Understanding Inflammation and Monitoring of Pharmacological Therapy in Children and Young Adults With Cystic Fibrosis.

15-F-Isoprostane, a reliable biomarker of oxidative stress, has been found elevated in exhaled breath condensate (EBC), a non-invasive technique for sampling of airway secretions, in patients with cystic fibrosis (CF). Azithromycin has antioxidant properties in experimental models of CF, but its effects on oxidative stress in CF patients are largely unknown. Primary objective of this pilot, proof-of-concept, prospective, parallel group, pharmacological study, was investigating the potential antioxidant effects of azithromycin in CF patients as reflected by EBC 15-F-isoprostane.

Extensive molecular analysis suggested the strong genetic heterogeneity of idiopathic chronic pancreatitis.

: Genetic features of Chronic Pancreatitis (CP) have been extensively investigated mainly testing genes associated to the trypsinogen activation pathway. However, different molecular pathways involving other genes may be implicated in CP pathogenesis. 80 patients with Idiopathic CP were investigated using Next Generation Sequencing approach with a panel of 70 genes related to six different pancreatic pathways: premature activation of trypsinogen; modifier genes of Cystic Fibrosis phenotype; pancreatic secretion and ion homeostasis; Calcium signalling and zymogen granules exocytosis; autophagy; autoimmune pancreatitis related genes.

Streptococcus pneumoniae oropharyngeal colonization in children and adolescents with cystic fibrosis.

Background: This study was designed to evaluate Streptococcus pneumoniae (S. pneumoniae) carriage rates in patients with cystic fibrosis (CF).

Methods: An oropharyngeal swab was obtained from 212 CF children and adolescents enrolled during routine clinical visits.

Glucose tolerance affects pubertal growth and final height of children with cystic fibrosis.

There are few data about the impact of cystic fibrosis-related diabetes (CFRD) on growth. We analyzed 17 children with cystic fibrosis (CF) presenting with newly diagnosed CFRD during puberty, in comparison with a matched control group of 52 CF children with normal glucose tolerance (NGT). Anthropometric evaluation showed that body mass index at CFRD diagnosis was significantly reduced in children with CFRD, in comparison with children with NGT (CFRD: -0.

ZnT8 antibodies in patients with cystic fibrosis: an expression of secondary beta-cell damage?

Cystic Fibrosis-Related Diabetes (CFRD) is caused by a severe insulin deficiency with associated different degrees of insulin resistance. Data concerning the potential impact of autoimmunity are conflicting. Ninety subjects with cystic fibrosis (CF) were tested for glucose tolerance and autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA2) and zinc transporter 8 (Znt8A).

Validation of a predictive survival model in Italian patients with cystic fibrosis.

Background: In 2001 Liou published a 5-year survival model using CFF Registry data.

Aims: To evaluate its validity in predicting survival in Italian CF patients.

Methods: In a retrospective study on 945 patients, the 9 variables selected by Liou were analyzed, vital status on December 2008 recorded and observed and expected deaths compared.

Fewer spontaneous arousals in infants with apparent life-threatening event.

Study Objectives: A deficit in arousal process has been implicated as a mechanism of sudden infant death syndrome (SIDS). Compared with control infants, SIDS victims showed significantly more subcortical activations and fewer cortical arousals than matched control infants. Apparent life-threatening event (ALTE) is often considered as an aborted SIDS event.

Arousal from sleep mechanisms in infants.

Arousals from sleep allow sleep to continue in the face of stimuli that normally elicit responses during wakefulness and also permit awakening. Such an adaptive mechanism implies that any malfunction may have clinical importance. Inadequate control of arousal in infants and children is associated with a variety of sleep-related problems.

Maturation of spontaneous arousals in healthy infants.

Objective: The propensity to arouse from sleep is an integrative part of the sleep structure and can have direct implications in various clinical conditions. This study was conducted to evaluate the maturation of spontaneous arousals during the first year of life in healthy infants.

Design: Nineteen infants were studied with nighttime polysomnography on 3 occasions: aged 2 to 3 months, 5 to 6 months, and 8 to 9 months.

NREM sleep instability is reduced in children with attention-deficit/hyperactivity disorder.

Study Objectives: To evaluate non-rapid eye movement sleep instability (NREM), as measured by the cyclic alternating pattern (CAP), in a cohort of children with attention-deficit/hyperactivity disorder (ADHD) and normal controls.

Design: Prospective study.

Settings: Sleep laboratory.

Spontaneous arousability in prone and supine position in healthy infants.

Study Objective: Compared with control infants, those who will be future victims of sudden infant death syndrome (SIDS) show a decreased arousability during sleep, with fewer cortical arousals and more-frequent subcortical activations. These findings suggest an incomplete arousal process in victims of SIDS. Prone sleep position, a major risk factor for SIDS, has been reported to reduce arousal responses during sleep.