Effect of elexacaftor-tezacaftor-ivacaftor on liver transient elastography, fibrosis indices and blood tests in children with cystic fibrosis.

Background: Elexacaftor-tezacaftor-ivacaftor (ETI) has significantly improved the clinical course of people with cystic fibrosis (pwCF) and eligible CFTR variants. In this study, we prospectively evaluated liver elastography, liver fibrosis indices and liver tests in children with CF aged 6-12 years started on ETI therapy.

Methods: Body mass index, sweat test, percent predicted forced expiratory volume in one second, serum markers of liver injury or portal hypertension, liver fibrosis indices, controlled attenuation parameter and liver stiffness were assessed before starting ETI and three and twelve months post-ETI, according to new international guidelines.

Reported Adverse Events in a Multicenter Cohort of Patients Ages 6-18 Years with Cystic Fibrosis and at Least One F508del Allele Receiving Elexacaftor/Tezacaftor/Ivacaftor.

Objective: The objective of this study was to describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers.

Study Design: This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included.

Microbiology of cystic fibrosis persons not chronically infected with : A quasi-experimental study on two different upper airways' sampling methods.

Background: The upper airways of cystic fibrosis (CF) persons are an evolutionary niche where genetically adapted bacterial strains are selected for lung infection. The microbiological studies conducted up to now on the upper airways are not easily comparable.

Methods: Using classical culture methods, we simultaneously studied the microbiological status of upper and lower airways in persons not chronically infected with .

Lung clearance index in children with cystic fibrosis previously diagnosed with CRMS/CFSPID: A monocentric prospective experience.

Introduction: No data are available on the values and role of lung clearance index (LCI) in cystic fibrosis (CF) Screen Positive Inconclusive Diagnosis (CFSPID) progressed to CF diagnosis (CFSPID > CF). This study aimed to assess the value of the LCI in correctly predicting the progression of CFSPID to CF.

Methods: This is a prospective study carried out at the CF Regional Center of Florence, Italy from September 1, 2019.

Nutritional Status and Circulating Levels of Fat-Soluble Vitamins in Cystic Fibrosis Patients: A Cohort Study and Evaluation of the Effect of CFTR Modulators.

Background: Improved therapy in CF has led to an overall improvement in nutritional status. The objectives of our study are: to cross-sectionally assess nutritional status and serum levels of fat-soluble vitamins; to retrospectively evaluate the efficacy of modulators on nutritional status and fat-soluble vitamin levels.

Methods: In patients younger than 2 years of age, we evaluated growth, in patients aged 2-18 years, we assessed BMI z-scores, and in adults, we assessed absolute BMI values.

Impact of Pancreatitis-Associated Protein on Newborn Screening Outcomes and Detection of CFTR-Related Metabolic Syndrome (CRMS)/Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID): A Monocentric Prospective Pilot Experience.

Pancreatitis-Associated Protein (PAP)-based Cystic Fibrosis (CF) newborn bloodspot screening (NBS) protocols detect less CFTR-Related Metabolic Syndrome (CRMS)/CF Screen Positive, Inconclusive Diagnosis (CFSPID). We prospectively evaluated the impact of PAP as the second step of the CF NBS protocol, before the CFTR genetic analysis, on NBS outcomes and CRMS/CFSPID detection in the Tuscany region, Italy. In parallel to the usual protocol (IRT/DNA, protocol 1), PAP was analyzed in IRT-positive infants (IRT/PAP/DNA, protocol 2) from 1 June 2020 until 31 May 2022.

Different management approaches and outcome for infants with an inconclusive diagnosis following newborn screening for cystic fibrosis (CRMS/CFSPID) and Pseudomonas aeruginosa isolation.

Introduction: Evidence is currently lacking to guide the management of cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome CF screen-positive inconclusive diagnosis (CRMS/CFSPID) with Pseudomonas aeruginosa (Pa)-positive respiratory culture. This study assessed the clinical data, management, and outcomes of an Italian cohort of CRMS/CFSPID infants with Pa isolated from their airways.

Methods: Data of Pa-positive CRMS/CFSPID infants born between January 2011 and August 2018 and followed at five CF Italian centres were retrospectively extracted.

Clinical outcomes of a large cohort of individuals with the F508del/5T;TG12 CFTR genotype.

Background: In recent years, patients with cystic fibrosis (CF) conductance regulator (CFTR) variant poly(T) sequences have been increasingly reported with a wide spectrum of clinical severity. We describe the long-term clinical outcomes and progression to a CF diagnosis over time in a large Italian cohort of patients carrying the CFTR F508del/5T;TG12 genotype.

Methods: A retrospective analysis of subjects from 10 CF centres in Italy with the F508del/5T;TG12 genotype was performed.

Outcomes of early repeat sweat testing in infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/CF screen-positive, inconclusive diagnosis.

Background: Reaching early and definitive diagnosis in infants with cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID) is a priority of all CF newborn screening programs. Currently, sweat testing (ST) is the gold standard for CF diagnosis or exclusion. We assessed outcomes in a cohort of Italian CRMS/CFSPID infants who underwent repeat ST in the 1st year of life.

A survey of the prevalence, management and outcome of infants with an inconclusive diagnosis following newborn bloodspot screening for cystic fibrosis (CRMS/CFSPID) in six Italian centres.

Objective: We evaluated the prevalence, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene profile, clinical data, management and outcome for infants with a CFTR-related metabolic syndrome/CF Screen Positive, Inconclusive Diagnosis (CRMS/CFSPID) designation from six Italian centres.

Methods: All newborn bloodspot screening (NBS) positive infants born from January 2011 to August 2018 with a CF diagnosis or a CRMS/CFSPID designation were enrolled. Data on sweat testing, genetics, clinical course and management were collected.

CRMS/CFSPID Subjects Carrying D1152H CFTR Variant: Can the Second Variant Be a Predictor of Disease Development?

Background: There are no predictive factors of evolution of cystic fibrosis (CF) screen positive inconclusive diagnosis subjects (CFSPIDs).

Aim: to define the role of the second variant as a predictive factor of disease evolution in CFSPIDs carrying the D1152H variant.

Methods: We retrospectively evaluated clinical characteristics and outcome of CFSPIDs carrying the D1152H variant followed at five Italian CF centers.

A New Versatile Water-Soluble Iniferter Platform for the Preparation of Molecularly Imprinted Nanoparticles by Photopolymerisation in Aqueous Media.

The multi-step synthesis of a new water-soluble dithiocarbamate iniferter platform for the preparation of nanoparticles and -gels in aqueous solvents by photoinduced living-radical polymerisation is described herein. The water solubility of the dithiocarbamate iniferter was achieved by incorporating two unprotected glucose units into the iniferter structure by copper(I)-catalysed azide-alkyne cycloaddition ("click chemistry"). Molecularly imprinted nanoparticles (MIPs) specific for 2,4-dichlorophenoxyacetic acid and the corresponding non-imprinted particles (NIPs) were prepared in pure water by using the prepared iniferter as photoinitiator.

A disposable evanescent wave fiber optic sensor coated with a molecularly imprinted polymer as a selective fluorescence probe.

We have developed a disposable evanescent wave fiber optic sensor by coating a molecularly imprinted polymer (MIP) containing a fluorescent signaling group on a 4-cm long polystyrene optical waveguide. The MIP is composed of a naphthalimide-based fluorescent monomer, which shows fluorescence enhancement upon binding with carboxyl-containing molecules. The herbicide 2,4-dichlorophenoxyacetic acid and the mycotoxin citrinin were used as model analytes.

Modulation of the microenvironment surrounding the active site of penicillin G acylase immobilized on acrylic carriers improves the enzymatic synthesis of cephalosporins.

The catalytic properties of penicillin G acylase (PGA) from Escherichia coli in kinetically controlled synthesis of β-lactam antibiotics are negatively affected upon immobilization on hydrophobic acrylic carriers. Two strategies have been here pursued to improve the synthetic performance of PGA immobilized on epoxy-activated acrylic carriers. First, an aldehyde-based spacer was inserted on the carrier surface by glutaraldehyde activation (immobilization yield = 50%).

Modulation of imprinting efficiency in nanogels with catalytic activity in the Kemp elimination.

The interactions between the template and the functional monomer are a key to the formation of cavities in the imprinted nanogels with high molecular recognition properties. Nanogels with enzyme-like activity for the Kemp elimination have been synthesized using 4-vinylpyridine as the functional monomer and indole as the template. The weak hydrogen bond interaction in the complex is shown to be able to induce very distinctive features in the cavities of the imprinted nanogels.

Characterization and study of the orientation of immobilized enzymes by tryptic digestion and HPLC-MS: design of an efficient catalyst for the synthesis of cephalosporins.

An innovative approach to determine the orientation of penicillin G acylase (PGA) from Escherichia coli covalently immobilized onto solid supports has been developed. This method is based on tryptic digestion of immobilized PGA followed by HPLC-MS analysis of the released peptides which are supposed to be only those exposed toward the reaction medium and not directly bound to the solid support. To this purpose, PGA was immobilized on Eupergit C (acrylic hydrophobic resin) and glyoxyl-agarose (hydrophilic resin) functionalized with epoxy and aldehyde groups, respectively, both involving the Lys residues of the protein.