Eur J Paediatr Neurol. 2025 Jan 11;54:130-139. doi: 10.1016/j.ejpn.2025.01.004. Online ahead of print.

ABSTRACT

BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder characterized by a progressive decline in muscle function, leading to loss of ambulation, respiratory and cardiac failure, and ultimately death. Improvements in DMD management have increased patient life expectancy; therefore, there is a growing requirement for patients to transfer from paediatric to adult care services. There is also a need for clear recommendations to guide this process.

AIM: To establish international consensus guidelines regarding best practices for transitioning patients with DMD from paediatric to adult care and ensuring continuity of treatment.

METHODS: Consensus statements were developed using the Delphi process and scored using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The initiative was led by a steering committee (one non-voting chair and two voting members) who recruited 15 expert panellists to form the consensus group. Following an initial systematic literature search, the consensus group voted in three voting rounds. Round 1 (free-text responses to questions) and Round 2 (importance ranking of statements) were completed using an online survey. Round 3 (voting on final consensus statements) took place during a virtual consensus meeting.

CONSENSUS STATEMENTS: Consensus was reached on 48 statements covering the topics of transition planning, the transition process, post-transfer management, communicating with young people with DMD and supporting them with the transition to adult life.

CONCLUSION: These consensus statements provide guidelines for improving transition practices for young people with DMD and promoting continued care at a comparable standard in adulthood.

PMID:39892019 | DOI:10.1016/j.ejpn.2025.01.004

Ther Adv Respir Dis. 2025 Jan-Dec;19:17534666251317200. doi: 10.1177/17534666251317200.

ABSTRACT

BACKGROUND: Cardiovascular disease (CVD) risks are increasing in people with cystic fibrosis (pwCF). While cholesterol levels were historically low in pwCF, higher levels after initiating highly effective modulator therapy (HEMT) have been reported. Mechanisms are unclear and there is little guidance on screening.

OBJECTIVES: To evaluate serum lipid changes at multiple timepoints after ivacaftor initiation, and to assess current screening practices for CVD risk factors among CF providers.

DESIGN: This was a post-hoc correlative analysis of prospectively collected clinical data and serum samples from the GOAL cohort study. Cross-sectional survey methodology was also employed.

METHODS: We evaluated serum lipids (total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) at baseline, 3- and 18 months after ivacaftor initiation using samples from the GOAL study biorepository. We also surveyed CF providers across the United States on their CVD risk screening practices.

RESULTS: Fifty GOAL participants' samples were analyzed. Using the repeated measures model, TC significantly varied by visit (p = 0.004), driven by a significant increase from baseline at 3 months (mean difference 9.4 mg/dL). This difference diminished by 18 months. BMI was a significant covariate for TC. No significant differences by visit were detected in LDL or HDL. Seventy-five respondents participated in the survey (response rate 5.6%; 41 adult providers, 18 pediatric providers, and 10 providers caring for both) with 67% reporting no lipid screening policy existed in their center. In the past year, 29% of adult providers prescribed lipid-lowering therapy, 54% started anti-hypertensive medications, and 48% initiated ischemic cardiac evaluations for pwCF.

CONCLUSION: TC significantly increased within 3 months of initiating ivacaftor, but subsequently diminished toward baseline by 18 months. Lipid screening practices among CF providers were variable and providers are increasingly being confronted with managing CVD risk factors. Partnering with primary care providers is likely to become increasingly important in CF care models.

PMID:39891563 | DOI:10.1177/17534666251317200

JAMA Netw Open. 2025 Jan 2;8(1):e2457341. doi: 10.1001/jamanetworkopen.2024.57341.

ABSTRACT

IMPORTANCE: Ultraprocessed foods (UPF), characterized as shelf-stable but nutritionally imbalanced foods, pose a public health crisis worldwide. In adults, UPF consumption is associated with increased obesity risk, but findings among children are inconsistent.

OBJECTIVES: To examine the associations among UPF intake, anthropometric adiposity indicators, and obesity status in Canadian children.

DESIGN, SETTING, AND PARTICIPANTS: In the CHILD Cohort Study, one of the largest prospective, multicenter, population-based pregnancy cohorts in Canada, diet was assessed during the 3-year visit (September 2011 to June 2016), and anthropometric measurements were assessed at the 5-year visit (December 2013 to April 2018). Data analysis was performed between July 1, 2023, and June 30, 2024.

EXPOSURE: Diet intake was assessed using a semiquantitative food frequency questionnaire at 3 years of age. UPFs were identified using the NOVA classification system.

MAIN OUTCOMES AND MEASURES: Anthropometric adiposity indicators were measured at 5 years of age and used to calculate age- and sex-standardized z scores for body mass index (BMI), waist to height ratio, and subscapular and triceps skinfold thicknesses, and obesity, which was defined using BMI z score cutoffs. Multivariable-adjusted regression analyses were used to examine the associations of UPF with adiposity and obesity development, accounting for parental, birth, and early-childhood factors.

RESULTS: Among 2217 participants included in this study, median age at the outcome assessment was 5.0 (IQR, 5.0-5.1) years, and 1175 (53.0%) were males. At 3 years of age, UPF contributed 45.0% of total daily energy intake. UPF energy contribution was higher in males vs females (46.0% vs 43.9%; P < .001). Among all participants, higher UPF intake at 3 years of age was associated with higher anthropometric adiposity indicators at 5 years of age, primarily driven by males. In males, every 10% UPF energy increase was associated with higher adiposity indicator z scores for BMI (β, 0.08; 95% CI, 0.03-0.14), waist to height ratio (β, 0.07; 95% CI, 0.01-0.12), and subscapular (β, 0.12; 95% CI, 0.06-0.18) and triceps (β, 0.09; 95% CI, 0.03-0.15) skinfold thickness and higher odds of living with overweight or obesity (odds ratio, 1.19; 95% CI, 1.03-1.36). No significant associations were observed among females.

CONCLUSIONS AND RELEVANCE: In this cohort study of Canadian children, high UPF consumption during early childhood was associated with obesity development, primarily in males. These findings can inform targeted public health initiatives for early childhood centers and caregiver education programs to reduce UPF intake and prevent obesity.

PMID:39888617 | PMC:PMC11786234 | DOI:10.1001/jamanetworkopen.2024.57341

FEMS Microbiol Lett. 2025 Jan 31:fnaf017. doi: 10.1093/femsle/fnaf017. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa has increasing clinical relevance and commonly occupies the cystic fibrosis (CF) airways. Its ability to colonize and persist in diverse niches is attributed to its large accessory genome, where prophages represent a common feature and may contribute to its fitness and persistence. We focused on the CF airways niche and used 197 longitudinal isolates from 12 patients persistently infected by P. aeruginosa. We computationally predicted intact prophages for each longitudinal group and scored their long-term persistence. We then confirmed prophage inducibility and mapped their location in the host chromosome with lysate sequencing. Using comparative genomics, we evaluated prophage genomic diversity, long-term persistence and level of genomic maintenance. Our findings support previous findings that most P. aeruginosa genomes harbour prophages some of which can self-induce, and that a common CF-treating antibiotic, ciprofloxacin, can induce prophages. Induced prophage genomes displayed high diversity and even genomic novelty. Finally, all induced prophages persisted long-term with their genomes avoiding gene loss and degradation over four years of host replication in the stressful CF airways niche. This and our detection of phage genes which contribute to host competitiveness and adaptation, lends support to our hypothesis that the vast majority of prophages detected as intact and inducible in this study facilitated their host fitness and persistence.

PMID:39890605 | DOI:10.1093/femsle/fnaf017

J Cyst Fibros. 2025 Jan 30:S1569-1993(25)00001-3. doi: 10.1016/j.jcf.2025.01.001. Online ahead of print.

ABSTRACT

BACKGROUND: CFTR modulator (CFTR-M) therapy has led to improved clinical outcomes amongst people with cystic fibrosis (PwCF) eligible for these therapies. However, there is limited data on their impact on the basic life needs and financial concerns of PwCF.

METHODS: We used data from the Wellness in the Modulator Era (Well-ME) survey, which includes data from 900 PwCF both taking and not taking CFTR-M. We examined self-reported financial well-being over time and changes associated with school or work, financial planning, and costs of living. Descriptive statistics were used to analyze responses.

RESULTS: Most respondents reported no change in financial well-being, but 13 % identified a positive change and 16 % reported a negative change. Positive changes in basic life needs included fewer missed work and school days, while negative changes included medical out-of-pocket costs. Worries about financial problems were reported in 35 % of all respondents and were more common in PwCF who never took CFTR-M or had been taking one and then stopped, in PwCF with lower lung function, and in PwCF with Medicaid insurance.

CONCLUSIONS: These results indicate that for most PwCF, CFTR-M have not affected their basic life needs, and a substantial proportion of PwCF continue to experience financial stress and concerns. Many respondents' financial concerns focused on medical costs and insurance. These data underscore the continued need for CF care teams to address PwCF's financial stress and ability to meet basic life needs, even in the era of improved physical health outcomes due to CFTR-M therapy.

PMID:39890522 | DOI:10.1016/j.jcf.2025.01.001

Acta Diabetol. 2025 Jan 31. doi: 10.1007/s00592-025-02457-8. Online ahead of print.

NO ABSTRACT

PMID:39888447 | DOI:10.1007/s00592-025-02457-8

J Cachexia Sarcopenia Muscle. 2025 Feb;16(1):e13708. doi: 10.1002/jcsm.13708.

ABSTRACT

BACKGROUND: Regenerative capacity of skeletal muscles decreases with age. Deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) is associated with skeletal muscle weakness as well as epithelial cell senescence. However, whether and how CFTR plays a role in skeletal muscle regeneration and aging were unclear.

METHODS: Vastus lateralis biopsy samples from male and female human subjects (n = 23) of 7- to 86-year-old and gastrocnemii tissues from mice of 4- to 29-month-old were examined for CFTR expression. Skeletal muscle tissues or cultured myoblasts from mice carrying CFTR mutation (DF508) at 4- to 18-month-old were used for assessment of muscle mass, contractile force and regenerative capacity as well as myogenic and autophagy signalling. Overexpression of LC3-β, an autophagy mediator, was conducted to reverse myogenic defects in DF508 myoblasts. Adenoviruses containing CFTR gene or pharmaceuticals that enhance CFTR (VX809) were locally injected into the gastrocnemius or femoris quadricep to rescue age-related skeletal muscle defects in mice.

RESULTS: mRNA levels of CFTR in human vastus lateralis exhibited significantly negative correlations with age (r = -0.87 in males and -0.62 in females, p < 0.05). Gastrocnemius mRNA level of CFTR decreased by 77.7 ± 4.6% in 29-month-old wild-type mice compared to the 4-month-old. At 18-month-old, DF508 mice showed significantly reduced lean mass (by 35.6%), lower specific twitch force of the gastrocnemius (by 46.2%), decrease in fast/slow-twitch muscle isoform ratio as well as downregulation of myogenic (e.g., MYOD and MYOG) or autophagy/mitophagy (e.g., LC3-β) genes, compared to age-matched wild-types. Post-injury gastrocnemius regeneration was found impaired in DF508 mice. Myoblast cultures from DF508 mice showed defective myogenic differentiation, which was reversed by overexpressing LC3-β. In aged (> 15-month-old) mice, overexpressing CFTR or VX809 restored the expression of autophagy or myogenic genes, increased mitochondrial LC3-β level and improved skeletal muscle mass and function.

CONCLUSION: Age-related reduction in skeletal muscle expression of CFTR impairs autophagy and myogenesis, exacerbating skeletal muscle aging. Enhancing CFTR might be a potential treatment strategy for age-related skeletal muscle disorders.

PMID:39887939 | DOI:10.1002/jcsm.13708

Ann Am Thorac Soc. 2025 Feb;22(2):311. doi: 10.1513/AnnalsATS.22i2Erratum.

NO ABSTRACT

PMID:39887697 | DOI:10.1513/AnnalsATS.22i2Erratum

Ann Am Thorac Soc. 2025 Feb;22(2):183-184. doi: 10.1513/AnnalsATS.202411-1229ED.

NO ABSTRACT

PMID:39887694 | DOI:10.1513/AnnalsATS.202411-1229ED

Sci Rep. 2025 Jan 30;15(1):3738. doi: 10.1038/s41598-025-86515-9.

ABSTRACT

Pyomelanogenic P. aeruginosa, frequently isolated from patients with urinary tract infections and cystic fibrosis, possesses the ability to withstand oxidative stress, contributing to virulence and resulting in persistent infections. Whole genome sequence analysis of U804, a pyomelanogenic, multidrug-resistant, clinical isolate, demonstrates the mechanism underlying pyomelanin overproduction. Seven essential oils (EOs) were screened for pyomelanin inhibition. Garlic, cinnamon and thyme EOs were selected for further studies based on their significant anti-virulent properties, like inhibition of pyomelanin production and biofilm formation. Additionally, downregulation of the expression of virulence genes regulated by quorum sensing (QS) and a decrease in levels of the QS signaling molecule, C12-HSL, were also observed. The EO treatment inhibited the survival of U804 in human blood and increased survival of C. elegans, a whole animal model of pathogenesis. EO treatment also resulted in a significant reduction of efflux pump activity, indicative of their effect on antibiotic sensitization. Garlic oil enhanced the permeability of the bacterial membrane, resulting in decreased survival, when combined with sub-MIC concentrations of colistin. This study demonstrates that thyme, cinnamon and garlic EOs can attenuate pyomelanogenic P. aeruginosa virulence traits. Additionally, garlic potentiates drug sensitivity, suggesting its promising therapeutic use in combating pyomelanogenic MDR infections.

PMID:39885214 | DOI:10.1038/s41598-025-86515-9

J Cyst Fibros. 2025 Jan 29:S1569-1993(25)00007-4. doi: 10.1016/j.jcf.2025.01.008. Online ahead of print.

ABSTRACT

BACKGROUND: People with cystic fibrosis (CF) are recommended to wear face-masks when in healthcare settings. We previously demonstrated that face-masks significantly reduce the release of Pseudomonas aeruginosa (P. aeruginosa) aerosols during coughing in adults with CF. There is a knowledge gap in relation to the impact of mask wear in children with CF. This study aimed to examine the tolerability and effectiveness in lowering emissions of hospital-grade surgical and one type of commercially available cotton face-mask in children with CF.

METHODS: Twenty children with CF and P. aeruginosa infection were recruited. Participants performed three cough manoeuvres in a validated cough aerosol system both with and without face-masks of differing wear time. Cough aerosols were sampled at two meters using an Andersen Cascade Impactor. Quantitative sputum and aerosol bacterial cultures were performed. Participants also rated the comfort levels of the face-masks.

RESULTS: P. aeruginosa was cultured from the sputum in eight participants (40 %). During uncovered coughing (reference manoeuvre), seven of the 20 participants produced aerosols containing bacterial pathogens. There was a reduction in aerosolised bacterial load during coughing with both surgical and cotton face-masks. The mean percent reduction in CFU with both types of face-masks was 82 % (95 % CI 56 - 108) during the immediate face-mask wear test compared to the uncovered cough test. Face-masks were generally well tolerated.

CONCLUSIONS: Face-masks are well tolerated and effective in reducing cough-generated bacterial aerosols in children with CF.

PMID:39884883 | DOI:10.1016/j.jcf.2025.01.008

BMJ Open Respir Res. 2025 Jan 30;12(1):e002522. doi: 10.1136/bmjresp-2024-002522.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is associated with a historically high treatment burden which causes anxiety and exhaustion for parents of children with CF, especially in the early years of a child's life. Recently, a new medication, elexacaftor/tezacaftor/ivacaftor (ETI), has become available to some people with CF, which has had a significant impact on the quality of life of older children and adults. This medication will soon be available for children ages 2-5 in the UK. This study investigated parents' perspectives before their children could start ETI.

METHOD: 10 parents of young children with CF participated in semistructured online focus groups. The data were analysed using thematic analysis to identify key themes.

RESULTS: Three reviewers identified four main themes: (1) The 'roller coaster' of parental emotions: Shock, hope, uncertainty and anticipation, (2) The dark side of the unknown, side effects and burden of decision making, (3) The value of simple pleasures in a life with CF; treatment burden, normality, future, family life and (4) Reforming clinical care in the new era of CF care; support, communication and the future.

CONCLUSION: Parents experience a range of emotions from the day of diagnosis. While ETI brings hope and positivity, parents are concerned about the medication's safety. Parents have clear hopes and wishes for their child's future and reflect on the need for clinicians to consider reforming clinical care in the new era of CF for those eligible for new therapies.

PMID:39884719 | DOI:10.1136/bmjresp-2024-002522

Infection. 2025 Jan 30. doi: 10.1007/s15010-025-02478-z. Online ahead of print.

ABSTRACT

BACKGROUND: Lung transplantation is the ultimate treatment option for patients with advanced cystic fibrosis. Chronic colonization of these recipients with multidrug-resistant (MDR) pathogens may constitute a risk factor for an adverse outcome. We sought to analyze whether colonization with MDR pathogens, as outlined in the German classification of multiresistant Gram-negative bacteria (MRGN), was associated with the success of lung transplantation.

METHODS: We performed a monocentric retrospective analysis of 361 lung transplantations performed in Homburg, Germany, between 1995 and 2020. All recipients with a main diagnosis of cystic fibrosis (n = 69) were stratified into two groups based on colonization with Pseudomonas aeruginosa in view of MRGN before transplantation: no colonization and colonization without (n = 23) or with (n = 46) resistance to three or four antibiotic groups (3MRGN/4MRGN). Multivariable analyses were performed including various clinical parameters (preoperative data, postoperative data).

RESULTS: CF patients colonized with multidrug-resistant pathogens (Pseudomonas aeruginosa) classified as 3MRGN/4MRGN had poorer survival (median survival 16 years (without MRGN) versus 8 years (with MRGN), P = 0.048). Extracorporeal support (P = 0.014, HR = 2.929), re-transplantation (P = 0.023, HR = 2.303), female sex (P = 0.019, HR = 2.244) and 3MRGN/4MRGN (P = 0.036, HR = 2.376) were predictors of poor outcomes in the multivariate analysis. Co-colonization with the mold Aspergillus fumigatus was further associated with mortality risk in the 3MRGN/4MRGN group (P = 0.037, HR = 2.150).

CONCLUSION: Patients with cystic fibrosis and MDR colonization (Pseudomonas aeruginosa) are risk candidates for lung transplantation, targeted diagnostics and tailored anti-infective strategies are essential for survival after surgery. MDR colonization as expressed by MRGN may help to identify patients at increased risk to improve the organ allocation process.

PMID:39883262 | DOI:10.1007/s15010-025-02478-z

Eur J Pediatr. 2025 Jan 30;184(2):161. doi: 10.1007/s00431-025-05969-1.

ABSTRACT

It is known that in most cases of congenital central hypoventilation syndrome (CCHS), apnoeas and hypoventilation occur at birth. Nevertheless, a detailed description of initial symptoms, including pregnancy events and diagnostic tests performed, is warranted in infants with neonatal onset of CCHS, that is, in the first month of life. The European Central Hypoventilation Syndrome Consortium created an online patient registry from which 97 infants (44 females) with CCHS of neonatal onset and PHOX2B mutation from 10 countries were selected. The typical pregnancy is characterized by polyhydramnios (44%), fetal heart rate abnormalities on cardiotocography (36%), emergency cesarean sections. (30%) and a normal gestational age (14% preterm birth). The typical findings within the first days are the presence of respiratory distress (96%), often necessitating rapid intubation (44%) and, less frequently, cardiopulmonary resuscitation at birth (14%). These symptoms lead to a suspicion of CCHS after (median [interquartile]) 7 days [4; 12] since birth that is confirmed by genotype testing at 32 days [22; 61]. Daytime evaluation of blood gas is a frequent assessment leading to CCHS suspicion (n = 61/97, 63%; 95% confidence interval: 52-72) while a polysomnography is obtained in 45/97 infants (46%, 95% confidence interval: 36-57), demonstrating NREM hypoventilation in 44/45 infants (98%).

CONCLUSION: Our multicentre descriptive study shows that polyhydramnios is overrepresented during pregnancy, rapid respiratory failure is the main symptom leading to intubation in approximately half of infants and daytime alveolar hypoventilation is the main indicator prompting genetic testing.

WHAT IS KNOWN: • The initial symptoms and exams leading to congenital central hypoventilation syndrome diagnosis have mainly been described in single centre studies.

WHAT IS NEW: • Our multicentre European study confirms that polyhydramnios is overrepresented during pregnancy and that polysomnography is obtained in half of the infants only.

PMID:39883186 | DOI:10.1007/s00431-025-05969-1

J Med Chem. 2025 Jan 30. doi: 10.1021/acs.jmedchem.4c02547. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which regulates ion and fluid transport across epithelial cells. Mutations lead to complications, with life-limiting lung disease being the most severe manifestation. Traditional treatments focused on managing symptoms, but advances in understanding CF's molecular basis led to small-molecule CFTR modulators. Ivacaftor, which is a potentiator, was approved for gating mutations. Dual combinations like ivacaftor/lumacaftor and ivacaftor/tezacaftor brought together a potentiator and a class 1 corrector for F508del homozygous patients. Triple-combination CFTR modulators, including ivacaftor/tezacaftor/elexacaftor with an additional class 2 corrector, are now the standard of care for most CF patients, transforming the outlook for this disease. These drugs stabilize and potentiate the CFTR protein, improving lung function, sweat chloride levels, quality of life, and survival. This Perspective discusses CFTR structure and mutations, biological assays, medicinal chemistry research in identifying CFTR modulators, and clinical data of these agents.

PMID:39882833 | DOI:10.1021/acs.jmedchem.4c02547

Int J Gen Med. 2025 Jan 25;18:391-402. doi: 10.2147/IJGM.S490196. eCollection 2025.

ABSTRACT

BACKGROUND: Bronchiectasis, a respiratory ailment, significantly impacts the life expectancy of individuals. This study aimed to explore the prevalence of multidrug-resistant organisms (MDROs) among bronchiectasis patients, the resistance patterns within various antibiotic classes, and the associated factors with these organisms.

METHODS: A retrospective observational analysis was conducted on adult bronchiectasis patients attending clinics at Jordan University Hospital. The diagnosis of bronchiectasis was established through lung Computerized Tomography (CT) scans and clinical symptom assessment.

RESULTS: The study encompassed 235 patients, revealing a notably higher occurrence of MDROs among non-cystic fibrosis patients compared to their counterparts (P-value=0.001). Additionally, MDROs showed significant associations with the usage of inhaled beta agonists, anti-cholinergics, corticosteroids, and inhaled antibiotics (P-value<0.050). Patients with MDROs experienced a significantly elevated mean number of hospitalizations, exacerbations, and antibiotic courses compared to their counterparts (P-value<0.050). Moreover, those with MDROs exhibited a higher incidence of requiring O2 device support and faced an increased risk of mortality (P-value<0.050).

CONCLUSION: The observational nature of our study limits the associations in our study. However, we provided evidence that it is imperative for clinicians to assess their bronchiectasis patients for MDRO risk factors, facilitating appropriate initial antibiotic selection. Nevertheless, the validation of MDRO risk factors necessitates further exploration through larger studies with extended follow-up periods.

PMID:39881954 | PMC:PMC11776428 | DOI:10.2147/IJGM.S490196

Case Rep Anesthesiol. 2025 Jan 21;2025:6388254. doi: 10.1155/cria/6388254. eCollection 2025.

ABSTRACT

Recent advancements in therapeutics and risk reduction in the management of cystic fibrosis have increased the life expectancy of cystic fibrosis patients to the fifth decade of life. As the life expectancy of cystic fibrosis patients has increased, more cystic fibrosis patients have opted to pursue pregnancy. Normal pregnancy is accompanied by physiological changes that affect anesthetic management. These normal physiological changes, combined with the pathological manifestations of cystic fibrosis, create a unique set of anesthetic challenges. Here, we report on the management and clinical course of a 37-year-old parturient with cystic fibrosis, focusing on the anesthetic approach.

PMID:39881848 | PMC:PMC11774568 | DOI:10.1155/cria/6388254

Sovrem Tekhnologii Med. 2024;16(4):38-44. doi: 10.17691/stm2024.16.4.04. Epub 2024 Aug 30.

ABSTRACT

The aim of the study was to search for the associations of benign unconjugated hyperbilirubinemia phenotype with rs1799945 (H63D), rs1800562 (C282Y), rs1800730 (S65C) mutations of HFE gene, rs113993960 (ΔF508) of CFTR gene, rs28929474 (PIZ), rs17580 (PIS) mutations of SERPINA1 gene.

MATERIAL AND METHODS: The study design is case-control. The group with Gilbert's syndrome (GS) phenotype (n=414; mean age - 36.7±15.9 years; 49.8% men) was formed by gastroenterologists, and included the individuals with unconjugated hyperbilirubinemia who underwent a standard clinical examination. The individuals with known causes of unconjugated hyperbilirubinemia were excluded from the group. The control group (n=429; mean age - 38.5±14.3 years; 52.2% men) was a random sampling from DNA banks of MONICA project participants, the screening of young people aged 25-44 and a one-time study of schoolchildren in Novosibirsk (Russia). DNA was isolated by phenol-chloroform extraction or by the express method (PROBA-RAPID-GENETIKA; DNA-Technology, Moscow, Russia) from venous blood. Genotyping of groups by nucleotide sequence rs1799945 (H63D), rs1800562 (C282Y), rs1800730 (S65C) of HFE gene, rs113993960 (ΔF508) of CFTR gene, rs28929474 (PIZ), rs17580 (PIS) of SERPINA1 gene was performed by polymerase chain reaction followed by the analysis of fragment length polymorphism on a polyacrylamide gel.

RESULTS: According to the genotypes and alleles of the variants rs1799945 (H63D), rs1800562 (C282Y), rs1800730 (S65C) of HFE gene, rs113993960 (ΔF508) of CFTR gene, rs28929474 (PIZ), rs17580 (PIS) of SERPINA1 gene, no statistically significant differences were found between the GS group and the control group (p>0.05).

CONCLUSION: Nucleotide sequence variants rs1799945 (H63D), rs1800562 (C282Y), rs1800730 (S65C) of HFE gene, rs113993960 (ΔF508) of CFTR gene, rs28929474 (PIZ), rs17580 (PIS) of SERPINA1 gene, or their combinations with rs3064744 of UGT1A1 gene were found to have no association with GS.

PMID:39881831 | PMC:PMC11773142 | DOI:10.17691/stm2024.16.4.04

J Cyst Fibros. 2025 Jan 28:S1569-1993(25)00012-8. doi: 10.1016/j.jcf.2025.01.012. Online ahead of print.

ABSTRACT

Pancreatic insufficiency is a major complication of cystic fibrosis (CF), which traditionally has been managed with pancreatic enzyme replacement therapy in the vast majority of CF patients, even in the era of highly effective cystic fibrosis transmembrane conductance regulator modulator (CFTRm) therapy. We report on a 1.7 year old male infant with CF who was exposed to ETI both in utero and postpartum, via breast milk and oral granules. Repeated faecal elastase analyses were carried out to monitor pancreatic function closely, with normal levels at birth. Although faecal elastase values fluctuated over time, it never dropped below 100 µg/g for several subsequent measurements, while the infant continued to receive breast milk. However, at the age of 8 months PERT was initiated. ETI was introduced at 9 months of age in the form of crushed tablets as an individualised treatment, following a sustained increase in faecal elastase to >200µg/g to date. 3 weeks after starting oral ETI therapy, PERT was discontinued. With this case report we would like to show that continuous pre- and postnatal ETI exposure can maintain pancreatic function in CF for at least 1.7 years.

PMID:39880765 | DOI:10.1016/j.jcf.2025.01.012

J Cyst Fibros. 2025 Jan 28:S1569-1993(25)00011-6. doi: 10.1016/j.jcf.2025.01.011. Online ahead of print.

ABSTRACT

BACKGROUND: Males with cystic fibrosis (MwCF) face general and disease-specific sexual and reproductive health (SRH) concerns. Using concept mapping (CM), this study identified the SRH topics valued by members of the CF community.

METHODS: MwCF 18 years and older, parents and partners of MwCF, and healthcare providers participated in an online CM study. Participants individually brainstormed, sorted, and rated SRH topics important for MwCF. Using multidimensional scaling, hierarchical cluster analyses, and t tests to assess rating differences, participants interpreted results during an online meeting.

RESULTS: Eighty-nine participants (32 MwCF; 6 parents; 9 partners; and 42 providers) generated 125 statements on male SRH in CF. Seventy-eight percent completed sorting and 73% rated statements based on importance. During interpretation, 20 participants named six clusters of SRH topics: 1) Family building and fertility; 2) Psychosocial aspects of SRH; 3) Being a parent or partner as a MwCF; 4) Sexual development, function, and treatments; 5) SRH education, communication, and awareness; and 6) SRH risks, comorbidities, and aging. Participants rated family building and fertility as highest in importance (mean = 4.06±0.36 of 5). Providers issued higher importance ratings compared to MwCF and parent/partner participants. Participants identified patient-centered outcomes for each cluster and focused on enhancing SRH knowledge, decision-making, and patient-provider communication in CF care.

CONCLUSIONS: The SRH topics, importance, and patient-centered outcomes identified in this study can inform future interventions and research to optimize the comprehensive clinical care delivery for MwCF.

PMID:39880764 | DOI:10.1016/j.jcf.2025.01.011