Expanding the Impact of New Cystic Fibrosis Therapies in Low- and Middle-Income Countries.

Background: Cystic fibrosis (CF) primarily affects Caucasian populations, with the highest prevalence in countries like Ireland, the UK, Australia, and Canada. Despite significant improvements in survival, pulmonary insufficiency remains the leading cause of death. Factors such as nutrition, chronic Pseudomonas aeruginosa (PsA) infection, genotype, pancreatic status, and cystic fibrosis-related diabetes affect pulmonary function across age groups.

Risk Factors for Developing Adenovirus-Associated Post-Infectious Bronchiolitis Obliterans.

Background: Risk factors for progression of adenovirus (AdV)-associated bronchiolitis (AdV-B) to post-infectious bronchiolitis obliterans (PIBO) are poorly defined. We aimed to investigate this in a multicenter cohort.

Methods: A multicenter hospital-based analysis included children admitted with AdV-B in Jerusalem during 2016-2022.

ERS statement on transition of care in childhood interstitial lung diseases.

Interstitial lung diseases (ILD) are a heterogeneous group of rare diffuse diseases affecting the lung parenchyma in children and adults. Childhood interstitial lung diseases (chILD) are often diagnosed at very young age, affect the developing lung, and can have different presentations and prognosis compared to adult forms of these diseases. In addition, chILD in many cases may apparently remit, and have a better response to therapy and better prognosis than adult ILD.

Maternal and fetal outcomes in multiparous women with Cystic Fibrosis.

Background: Quality of life and survival in Cystic Fibrosis (CF) have improved dramatically, making family planning a feasible option. Maternal and perinatal outcomes in women with CF (wwCF) are similar to those seen in the general population. However, the effect of undergoing multiple pregnancies is unknown.

ECFS standards of care on CFTR-related disorders: Towards a comprehensive program for affected individuals.

After three publications defining an updated guidance on the diagnostic criteria for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorders (pwCFTR-RDs), establishing its relationship to CFTR-dysfunction and describing the individual disorders, this fourth and last paper in the series addresses some critical challenges facing health care providers and pwCFTR-RD. Topics included are: 1) benefits and obstacles to collect data from pwCFTR-RD are discussed, together with the opportunity to integrate them into established CF-registries; 2) the potential of infants designated CRMS/CFSPID to develop a CFTR-RD and how to communicate this information; 3) a description of the challenges in genetic counseling, with particular regard to phenotypic variability, unknown long-term evolution, CFTR testing and pregnancy termination 4) a proposal for the assessment of potential barriers to the implementation and dissemination of the produced documents to health care professionals involved in the care of pwCFTR-RD and a process to monitor the implementation of the CFTR-RD recommendations; 5) clinical trials investigating the efficacy of CFTR modulators in CFTR-RD and how endpoints and outcomes might be adapted to the heterogeneity of these disorders.

Cystic fibrosis in Europe: improved lung function and longevity - reasons for cautious optimism, but challenges remain.

Background: Prognosis and disease severity in cystic fibrosis (CF) are linked to declining lung function. To characterise lung function by the number of adults in countries with different levels of Gross National Income (GNI), data from the European Cystic Fibrosis Society Patient Registry were utilised.

Methods: Annual data including age, forced expiratory volume in 1 s (FEV), anthropometry, genotype, respiratory cultures and CF-related diabetes (CFRD) were retrieved between 2011 and 2021.

The new face of cystic fibrosis in the era of population genetic carrier screening.

Background: Population genetic carrier screening (PGCS) for cystic fibrosis (CF) has been offered to couples in Israel since 1999 and was included in a fully subsidized national program in 2008. We evaluated the impact of PGCS on CF incidence, genetic and clinical features.

Methods: This was a retrospective national study.

Nonsense mutations accelerate lung disease and decrease survival of cystic fibrosis children.

Rationale: Limited information is available on the clinical status of people with Cystic Fibrosis (pwCF) carrying 2 nonsense mutations (PTC/PTC). The main objective of this study was to compare disease severity between pwCF PTC/PTC, compound heterozygous for F508del and PTC (F508del/PTC) and homozygous for F508del (F508del+/+).

Methods: Based on the European CF Society Patient Registry clinical data of pwCF living in high and middle income European and neighboring countries, PTC/PTC (n = 657) were compared with F508del+/+ (n = 21,317) and F508del/PTC(n = 4254).

Clinical and functional efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis carrying the N1303K mutation.

Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) significantly improves health outcomes in people with cystic fibrosis (pwCF) carrying one or two F508del mutations. According to in vitro assays performed in FRT cells, 178 additional mutations respond to ELX/TEZ/IVA. The N1303K mutation is not included in this list of mutations.

Pediatric respiratory admissions and related viral infections during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has affected the incidence of respiratory viral infections. Our aim was to assess changes in pediatric admissions due to respiratory diseases and associated respiratory viral infections.

Methods: An observational study including all respiratory admissions to the pediatric departments from January 2015 to August 2021.

The association between Attention-Deficit-Hyperactivity-Disorder (ADHD) symptoms and disease severity in people with Cystic Fibrosis (pwCF).

Background: The hallmarks of Cystic fibrosis (CF), chronic infection and inflammation, require intensive daily treatment to maintain and improve quality of life and outcome. The incidence of Attention Deficit/Hyperactivity Disorder (ADHD) is increased in chronic inflammatory diseases. Previous studies suggested that the prevalence of ADHD in people with CF (pwCF) is higher than in the general population.

Acute pancreatitis in pancreatic-insufficient cystic fibrosis patients treated with CFTR modulators.

Cystic fibrosis transmembrane conductance regulator modulator therapy is associated with substantial clinical benefit and improved quality of life in patients with cystic fibrosis (CF). While their effect on lung function has been clearly reported, we are still in the process of unraveling the full impact they have on the pancreas. We present two cases of pancreatic-insufficient CF patients who presented with acute pancreatitis shortly after commencing elexacaftor/tezacaftor/ivacaftor modulator therapy.

Mothers' Knowledge of Infants' Fever Management: A National Prospective Study.

Objectives: The aim of this study was to describe mothers' knowledge of infant fever management after birth and six months later and its association with sociodemographic characteristics, perceived support, sources of consultation and health education; and to assess determinants of change in mother's knowledge from birth to six months.

Methods: Mothers (n = 2804) answered a self-reporting questionnaire after giving birth in maternity wards in six hospitals in Israel; six months later follow- up interviews were conducted by telephone.

Results: The mothers' knowledge level of infant fever management was low after birth (mean = 50.

Clinical outcomes associated with Achromobacter species infection in people with cystic fibrosis.

Background: Achromobacter species are emerging pathogens isolated from respiratory samples of Patients with cystic fibrosis (pwCF) causing growing concerns in the CF community. The epidemiology and the clinical impact of Achromobacter in CF is unclear since data are restricted to small case control studies or selected populations.

Aim: To characterize the effect of Achromobacter respiratory infection on CF lung disease.

The clinical yield of bronchoscopy in the management of cystic fibrosis: A retrospective multicenter study.

Background: Pulmonary disease is the leading cause of morbidity and mortality in people with cystic fibrosis (pwCF). Several studies have shown no benefit for bronchoscopy and bronchoalveolar lavage (BAL) over sputum to obtain microbiological cultures, hence the role of bronchoscopy in pwCF is unclear.

Aim: To analyze how bronchoscopy results affected clinical decision-making in pwCF and assess safety.

The utility of glucose area under the curve from the oral glucose tolerance test as a screening tool for cystic fibrosis-related diabetes.

Background: Consistently abnormal glucose levels on oral glucose tolerance test (OGTT) are the most effective screening tool for cystic fibrosis-related diabetes (CFRD). However, some cystic fibrosis (CF) patients demonstrate abnormal glucose profiles not reaching levels required for CFRD diagnosis and are, therefore, left untreated. Since CFRD is associated with disease deterioration, early diagnosis and treatment are desirable.

Disease severity of people with cystic fibrosis carrying residual function mutations: Data from the ECFS Patient Registry.

Rational: People with cystic fibrosis carrying residual function (RF) mutations are considered to have a mild disease course. This may influence caregivers and patients on how intensive the treatments should be.

Objectives: Characterize disease severity of patients carrying RF mutations, using the European CF Society Patient Registry (ECFSPR) data.

Enhancing the primary care pediatrician's role in managing psychosocial issues: a cross sectional study of pediatricians and parents in Israel.

Background: Psychosocial issues are an integral part of children's health and well-being, and it is widely acknowledged that pediatricians should be involved in their management. We examined the current perception of the pediatrician's role in the management of psychosocial problems in Israel from the perspective of parents and pediatricians, and identified possible barriers.

Methods: We assessed parents' and pediatricians' perspectives through a cross sectional survey.

Evaluation of sparing the pronator quadratus for volar plating of distal radius fractures: a retrospective clinical study.

Background: The most commonly used approach for distal radius fractures is the traditional Henry approach. However, it requires an intraoperative incision of the pronator quadratus (PQ) muscle, which results in a series of complications if the repair of the PQ fails.

Aim: The objective of this study was to investigate the efficacy of sparing the pronator quadratus for volar plating of the distal radius fractures.

Calcium carbonate mineralization is essential for biofilm formation and lung colonization.

Biofilms are differentiated microbial communities held together by an extracellular matrix. μCT X-ray revealed structured mineralized areas within biofilms of lung pathogens belonging to two distant phyla - the proteobacteria and the actinobacteria . Furthermore, calcium chelation inhibited the assembly of complex bacterial structures for both organisms with little to no effect on cell growth.

Antisense oligonucleotide splicing modulation as a novel Cystic Fibrosis therapeutic approach for the W1282X nonsense mutation.

Background: Antisense oligonucleotide- based drugs for splicing modulation were recently approved for various genetic diseases with unmet need. Here we aimed to generate skipping over exon 23 of the CFTR transcript, to eliminate the W1282X nonsense mutation and avoid RNA degradation induced by the nonsense mediated mRNA decay mechanism, allowing production of partially active CFTR proteins lacking exon 23.

Methods: ∼80 ASOs were screened in 16HBEge W1282X cells.