Combined CAR-T/HSCT approach in a patient with refractory acute lymphoblastic leukemia and cystic fibrosis.

Introduction: The association of acute lymphoblastic leukaemia (ALL) and cystic fibrosis (CF) is rare. We present the case of a paediatric patient affected by CF and refractory B-cell precursor (BCP) ALL, who was treated with combined chimeric antigen receptor T-cells (CAR-T) and allogeneic haematopoietic stem cell transplantation (HSCT).

Case Description: Autologous-CD19 targeting CAR-T allowed to achieve molecular remission and spare chemo-related toxicity.

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.

Risk of CFTR-related disorders and cystic fibrosis in an Italian cohort of CRMS/CFSPID subjects in preschool and school age.

Unlabelled: The identification of cystic fibrosis screening-positive, inconclusive diagnosis (CFSPID) in infants is a controversial outcome of newborn screening for cystic fibrosis (CF). Today, despite improvements in the knowledge of CFSPID and the description of several cohorts, little data are available on cohorts with a follow-up period of more than 6 years. In this study, we report the outcomes of an Italian cohort of CFSPID individuals with CFSPID or formerly CFTR-related disorders (CFTR-RD) (CFSPID > CFTR-RD) or diagnosed with CF (CFSPID > CF).

Cystic fibrosis and CFTR-related disorder with electrolyte imbalance at diagnosis: clinical features and outcome in an Italian cohort.

Unlabelled: There is limited information available on the clinical data, sweat test trends, and outcomes of individuals with cystic fibrosis (CF) who present with an isolated episode of hypoelectrolytemia with metabolic alkalosis (HMA). This study describes a cohort of Italian individuals with HMA as presenting symptom. The study is a retrospective multicenter analysis of individuals who presented with HMA as an initial symptom and was followed at 8 Italian CF Centers, from March 1988 to March 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.

Remote support by multidisciplinary teams: A crucial means to cope with the psychological impact of the SARS-COV-2 pandemic on patients with cystic fibrosis and inflammatory bowel disease in Lombardia.

Background: During Coronavirus Disease 2019 (COVID-19) outbreak in Lombardia, people were recommended to avoid visiting emergency departments and attending routine clinic visits. In this context, it was necessary to understand the psychological reactions of patients with chronic diseases. We evaluated the psychological effects on patients with chronic respiratory conditions and inflammatory bowel disease (IBD) through the analysis of their spontaneous contacts with their referral centres.

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.

Night Blindness in Cystic Fibrosis: The Key Role of Vitamin A in the Digestive System.

Vitamin A is a fundamental micronutrient that regulates various cellular patterns. Vitamin A deficiency (VAT) is a worldwide problem and the primary cause of nocturnal blindness especially in low income countries. Cystic fibrosis (CF) is a known risk factor of VAD because of liposoluble vitamin malabsorption due to pancreatic insufficiency.

Successful ceftazidime-avibactam treatment of post-surgery Burkholderia multivorans genomovar II bacteremia and brain abscesses in a young lung transplanted woman with cystic fibrosis.

Burkholderia cepacia complex (Bcc) includes several phenotypically similar but genotypically distinct gram-negative bacteria (GNB) that can colonize the respiratory tract of Cystic Fibrosis (CF) patients. Pathogens are difficult to treat due to intrinsic resistance to multiple antibiotics and are associated to a more rapid decline in lung function and to increased mortality, particularly after lung transplantation. For all these reasons, chronic infection by Burkholderia (B) cenocepacia is presently considered a relative or absolute contraindication in almost all lung transplant centres.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in two young children: the importance of an early diagnosis.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a serious life-treating condition characterized by skin eruption, fever, haematologic abnormalities, and multi-organ involvement that can be fatal if unrecognized, especially in patients with liver failure. Diagnosis may be difficult because it is rarely described in children and can mimic many different conditions.

Case Presentation: We report two cases of DRESS syndrome due to prolonged antibiotic treatment in young children in whom recovery occurred following different therapeutic approaches.

Efficacy and tolerability of a new nasal spray formulation containing hyaluronate and tobramycin in cystic fibrosis patients with bacterial rhinosinusitis.

Background: Chronic rhinosinusitis is common in cystic fibrosis (CF), as CFTR defects equally affect the airway and sinonasal mucosa. However, therapeutic strategies for CF-associated chronic rhinosinusitis lag behind current approaches for pulmonary disease.

Objective: To assess the tolerability and efficacy of a nasal spray formulation containing 0.

Insulin secretion, nutritional status and respiratory function in cystic fibrosis patients with normal glucose tolerance.

Background & Aims: Impaired growth and nutritional status in CF may be related to progressive insulin deficiency before CF-Related Diabetes has established. Aim of this study was to analyse the association of circulating insulin with nutritional status and lung function in CF patients with normal glucose tolerance (NGT).

Methods: We performed OGTT in 152 consecutive CF patients aged 8-20 years: 115 of them had NGT and were included in the study.

A wide methodological approach to identify a large duplication in CFTR gene in a CF patient uncharacterised by sequencing analysis.

Background: PCR-based diagnostic procedures are not able to characterise 6% of CF alleles. Recently, the application of array-CGH and of CFTR mRNA analysis has allowed the identification of new copy number mutations and splicing defects, that account for 2% and 13% of CF alleles, respectively, in the Italian population.

Methods: Here, we report the characterisation of a large duplication in CFTR gene through different methods: MLPA assay, RT-PCR and high-resolution array-CGH.

Analysis of inflammatory and immune response biomarkers in sputum and exhaled breath condensate by a multi-parametric biochip array in cystic fibrosis.

Cystic Fibrosis (CF) lung disease is characterized by high levels of cytokines and chemokines in the airways, producing chronic inflammation. Non-invasive biomarkers, which are also specific for the inflammatory and immune responses, are urgently needed to identify exacerbations and evaluate therapeutic efficacy. The aim of this study is to evaluate the association of sputum and exhaled breath condensate (EBC) biomarker changes with clinical exacerbation and response to therapy.

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients.

Background: Cystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.

Aim: To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.

Methods: A total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations.

A novel donor splice site characterized by CFTR mRNA analysis induces a new pseudo-exon in CF patients.

Background: The CFTR gene is tightly regulated and differentially expressed in many mucosal epithelial cell types. There is evidence of an increasing number of genomic variations in the intronic regions influencing mRNA splicing, and also the level of normal CFTR transcript.

Methods: In the present study, we investigate the molecular defect by RT-PCR analyzing the mRNA of 25 cystic fibrosis (CF) patients in whom only one or no CF allele had been identified after DNA analysis (of all the exons of the CFTR gene).

Molecular and clinical features associated with CFTR gene rearrangements in Italian population: identification of a new duplication and recurrent deletions.

Cystic fibrosis (CF) is mainly caused by small deletions or missense mutations in the CFTR gene. The CF mutation database lists more than 35 large rearrangements that may escape detection using polymerase chain reaction-base techniques. The Innogenetics assay, the denaturing high-performance liquid chromatography and sequencing screening showed a mutation detection rate of 92.

Clinical and economic impact of influenza vaccination on healthy children aged 2-5 years.

This paper reports the data concerning the net economic cost savings attributable to influenza vaccination in healthy children aged 2-5 years, and may be useful when deciding the best recommendations for the use of influenza vaccine in pediatrics. A total of 303 previously unprimed healthy children aged 2-5 years (163 males; mean age+/-S.D.