bioRxiv [Preprint]. 2025 Jun 24:2025.06.18.660463. doi: 10.1101/2025.06.18.660463.

ABSTRACT

Cystic Fibrosis (CF) is caused by loss-of-function mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel predominantly expressed on the apical membrane of epithelial cells. Reduced Cl - and HCO 3 - secretion due to dysfunctional CFTR results in a decrease in lung function and is the leading cause of morbidity in individuals with CF. Recent therapies, known as highly effective CFTR modulator therapy (HEMT), help improve the lung function in individuals with specific CF-causing mutations by enhancing the folding, trafficking, and gating of CFTR. However, variability in HEMT responsiveness leads to sub-optimal clinical outcomes in some people with CF undergoing modulator therapy. A potential strategy is to complement their function with a CFTR-independent mechanism. One possibility is the use of ion channel-forming small molecules such as amphotericin B, which has shown promise in restoring function and host defenses in CF airway disease models. Amphotericin B functions as a molecular prosthetic for CFTR and may thus complement CFTR modulators. Here we show that co-treatment of CF airway epithelia with HEMT and amphotericin B results in greater increases in both HCO 3 - secretory flux and ASL pH compared to treatment with either agent alone. These findings suggest that co- administration of CFTR modulators and molecular prosthetics may provide additive therapeutic benefits for individuals with CF.

PMID:40667211 | PMC:PMC12262498 | DOI:10.1101/2025.06.18.660463

Oncoimmunology. 2025 Dec;14(1):2533488. doi: 10.1080/2162402X.2025.2533488. Epub 2025 Jul 15.

ABSTRACT

HER3-DXd and T-DXd are antibody-drug conjugates (ADCs) that induce immunogenic cell death and bystander killing, enhancing antitumor immunity beyond target-specific cytotoxicity. These findings highlight novel mechanisms that can overcome antigen heterogeneity and suggest opportunities for improving ADC design and therapeutic synergy through informed combination with immunotherapies.

PMID:40662767 | PMC:PMC12269677 | DOI:10.1080/2162402X.2025.2533488

Glycoconj J. 2025 Jul 15. doi: 10.1007/s10719-025-10191-0. Online ahead of print.

ABSTRACT

Cystic Fibrosis (CF), a life-threatening hereditary disease, arises from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes a chloride-conducting channel widely expressed in epithelial cells. The most common mutation, F508del, causes CFTR misfolding, premature degradation, and impaired mucociliary clearance, leading to recurrent respiratory infections and inflammation. The triple combination therapy with Elexacaftor, Tezacaftor, and Ivacaftor (ETI) has revolutionized CF management by partially restoring mutated CFTR function. However, enhancing CFTR rescue and stabilizing host immune responses remain critical challenges. In airway epithelial cells, CFTR interacts with proteins and lipids in macromolecular complexes that influence its stability. Among these, the ganglioside GM1 plays a key role in modulating plasma membrane protein dynamics, including CFTR. This study investigates the effects of exogenous GM1 supplementation as an adjuvant to ETI treatment. Our results demonstrate that GM1 enhances F508del-CFTR maturation and stability, even under Pseudomonas aeruginosa infection, which typically suppresses CFTR expression and function. Furthermore, GM1 restores xenophagic activity in bronchial epithelial cells, improving host defence mechanisms against the bacteria. These findings underscore the therapeutic potential of GM1 and its analogues in optimizing the plasma membrane environment for CFTR correction, suggesting that by enhancing the efficacy of CFTR modulators, GM1 could pave the way for innovative approaches to improve CF management.

PMID:40663265 | DOI:10.1007/s10719-025-10191-0

Expert Rev Respir Med. 2025 Jul 15. doi: 10.1080/17476348.2025.2535764. Online ahead of print.

ABSTRACT

INTRODUCTION: Vitamin D deficiency is common in cystic fibrosis (CF) and may be linked to disease severity. We aimed to investigate the association between vitamin D deficiency and severity in non-CF bronchiectasis.

METHODS: A systematic search of PubMed and Scopus (up to December 2024) identified relevant studies. After screening 170 articles, seven met the inclusion criteria. Study quality was assessed using NIH tools.

RESULTS: Patients with non-CF bronchiectasis had significantly lower serum 25-hydroxyvitamin D (25OHD) levels compared to healthy controls. In one study, median 25OHD was 24.7 nmol/L in patients vs. 45.3 nmol/L in controls. Another reported mean levels of 14.7 ± 9.6 ng/mL vs. 19.8 ± 6.9 ng/mL, respectively. Disease severity was assessed using validated and semi-structured measures, including the bronchiectasis severity index (BSI), number of exacerbations, pulmonary function tests (PFTs), radiological scores (Bhalla, modified Reiff), and health-related quality-of-life (HRQL) tools. Most studies reported worse severity outcomes in vitamin D-deficient patients.

CONCLUSIONS: Although vitamin D deficiency appears to be associated with more severe non-CF bronchiectasis, heterogeneity between studies limits definitive conclusions. Future studies should incorporate standardized tools such as the eFACED score to better characterize disease severity.

PMID:40662885 | DOI:10.1080/17476348.2025.2535764

Pediatr Pulmonol. 2025 Jul;60(7):e71208. doi: 10.1002/ppul.71208.

NO ABSTRACT

PMID:40662499 | DOI:10.1002/ppul.71208

Pediatr Pulmonol. 2025 Jul;60(7):e71190. doi: 10.1002/ppul.71190.

ABSTRACT

BACKGROUND: The HERO-2 study is a prospective, observational study investigating chronic daily therapy (CDT) changes among people with cystic fibrosis (PwCF) ≥ 12 years of age taking elexacaftor/tezacaftor/ivacaftor (ETI). The goal of this analysis was to describe baseline characteristics and patterns of CDT discontinuation reported at study enrollment and identify clinical features associated with CDT discontinuation.

METHODS: Study participants were recruited through their CF center, community engagement, or a smartphone application (Folia Health). Study enrollment and participation took place remotely through Folia Health. Participants gave consent to link their data with the CF Foundation Patient Registry (CFFPR). At enrollment, participants completed a baseline survey describing CDT use since starting ETI. Descriptive statistics were used to summarize HERO-2 participant characteristics. Logistic regression evaluated the association of selected individual characteristics with odds of CDT discontinuation.

RESULTS: A total of 860 PwCF enrolled in HERO-2, and 755 (87.8%) completed the enrollment survey and were linked to the CFFPR. At enrollment, 313 participants (41.5%) reported discontinuation of at least one CDT. The most frequently discontinued CDT was airway clearance (22.4%). Intravenous (IV) antibiotic treatment for a pulmonary exacerbation in the prior year and public insurance were associated with lower odds of CDT discontinuation.

CONCLUSIONS: In this large cohort of PwCF taking ETI, approximately 42% reported discontinuation of at least one CDT. Providers should be aware of these CDT discontinuation patterns and engage in open dialogue with PwCF and their families about CDT de-escalation.

PMID:40662498 | DOI:10.1002/ppul.71190

ERJ Open Res. 2025 Jul 14;11(4):00113-2025. doi: 10.1183/23120541.00113-2025. eCollection 2025 Jul.

ABSTRACT

Bronchiectasis pathogens in Taiwan have implications on clinical outcomes https://bit.ly/4iCDeK6.

PMID:40661932 | PMC:PMC12257154 | DOI:10.1183/23120541.00113-2025

Can Respir J. 2025 Jul 1;2025:8893074. doi: 10.1155/carj/8893074. eCollection 2025.

ABSTRACT

Introduction: The Canadian Cystic Fibrosis Registry (CCFR) was developed in the 1970s and has longitudinal demographic and clinical data on persons living with cystic fibrosis (CF) attending accredited clinics in Canada. We aimed to validate the data collection and identify potential limitations of the CCFR. Methods: Of 40 accredited CF clinics in Canada invited and based on an a priori sample size calculation, eight clinics were included. 15% of each CF clinic's population in 2019 were randomly selected. Data variables were selected based on their importance to care, epidemiologic trends, and data related to demography, clinic visits, and hospitalizations. The accuracy of the registry data was compared to the medical records as the gold standard. Each data element was categorized as correct, incorrect, or not able to be validated. The accuracy rate was calculated as the percent correct out of all records validated. Results: A total of 4382 individuals had data entered into the CCFR in 2019. The validation cohort consisted of 208 individuals from 8 clinics, which were representative across location, size of clinic (small/medium/large), and type of clinic (adult, pediatric, and combined). The 208 individuals were 52% male and 95% White, and with a median age of 26.3 years (IQR: 15.2-36.6). Approximately 95% of CCFR data on clinical measurements, infections, treatments, and hospitalizations validated were accurate as compared to the medical record. For demography, sex and date of birth had 100% accuracy. Conclusion: Our validation of the CCFR demonstrated high accuracy for clinical and demographic variables used in clinical research.

PMID:40661671 | PMC:PMC12259333 | DOI:10.1155/carj/8893074

bioRxiv [Preprint]. 2025 Jun 12:2025.06.11.659172. doi: 10.1101/2025.06.11.659172.

ABSTRACT

Cryogenic electron microscopy (cryo-EM) analysis of bacteriophages is a valuable method for deciphering virus composition and conformational plasticity. In this study, we present a high-resolution structural atlas of the Pseudomonas virus Pa223, a phage from the Bruynoghevirus genus that has recently been used in clinical cocktails for treating cystic fibrosis and non-cystic fibrosis bronchiectasis, as well as for compassionate care. By combining bioinformatics, proteomics, cryo-EM single particle analysis, and localized reconstruction, we annotated and built atomic models for eight structural polypeptide chains that form the icosahedral capsid and noncontractile tail. We discovered that the Pa223 capsid is decorated by a spike protein that features a unique triple-β helix fold with no structural homologs in the database. The Pa223 tail features six trimeric tail fibers extending upwards, similar to, but shorter than, those found in phage T7. Unlike T7, the Pa223 tail is extended by two head-to-tail adaptors and sealed by a trimeric tail needle, similar to P22-like phages. We identified a protein bound around the outer perimeter of the portal protein, positioned similarly to the ejection protein gp72, which was identified in the Pseudomonas phage DEV, a Litunavirus phage and member of the reclassified Schitoviridae family. This structural hint led us to identify the Pa223 ejection proteins gp53, gp54, and gp56, which bioinformatically resemble those of T7-like phages more closely than Schitoviridae . Thus, phage Pa223 contains diverse structural elements found in P22-like, T7-like, and Litunavirus phages, providing a framework for understanding the diversification and evolution of ejection proteins in Bruynogheviruses .

HIGHLIGHTS: The high-resolution structure of Bruynoghevirus Pa223 reveals hybrid structural features that are shared among P22-like, T7-like, and Litunavirus phages. The Pa223 capsid is decorated with a trimeric spike asymmetrically bound at the icosahedral 3-fold axes.The Pa223 tail features two quasi-equivalent conformations of the head-to-tail adaptor protein arranged into two coaxial rings. Identification of the ejection protein gp54 through structural similarity to gp72 from the Litunavirus DEV. Bioinformatic mapping of the Pa223 ejection proteins gp53 and gp56 validated through mass spectrometry analysis of infectious virions.

PMID:40661476 | PMC:PMC12259138 | DOI:10.1101/2025.06.11.659172

Nat Rev Clin Oncol. 2025 Jul 14. doi: 10.1038/s41571-025-01052-8. Online ahead of print.

ABSTRACT

Radiotherapy has an established role in the clinical treatment of patients with a variety of cancers owing to the ability to preferentially kill malignant cells mostly while sparing their non-malignant counterparts. Results from phase I-II trials also suggest that radiotherapy can have therapeutically relevant immunostimulatory effects, especially when combined with immune-checkpoint inhibitors. Over the past two decades, evidence has emerged showing that intestinal microbial communities have a major influence on the immunological tonus of patients with cancer and can influence sensitivity to various immunotherapies, including immune-checkpoint inhibitors and chimeric antigen receptor T cells. Here, we critically discuss the effects of such microbial ecosystems on radiotherapy-induced toxicities and tumour-targeting immune responses, with a focus on the clinical potential of these relationships for predictive and therapeutic clinical applications.

PMID:40659791 | DOI:10.1038/s41571-025-01052-8

Eur Respir J. 2025 Jul 14;66(1):2500793. doi: 10.1183/13993003.00793-2025. Print 2025 Jul.

NO ABSTRACT

PMID:40659466 | DOI:10.1183/13993003.00793-2025

Transfusion. 2025 Jul 14. doi: 10.1111/trf.18318. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies show that extracorporeal photopheresis (ECP) might benefit chronic lung allograft dysfunction (CLAD). A standard ECP cycle consists of two consecutive procedures regardless of the technique employed.

STUDY DESIGN AND METHODS: Evaluation of ECP cycle (from two to one procedure) modification due to pandemic restrictions in 25 patients with CLAD under chronic treatment by off-line ECP in the 6 months preceding cycle modification (one procedure processing 1.5 patients blood volumes [1.5 ECP]). Assessment of any significant change in lung function decline and the relationship with product characteristics compared to pre-ECP cycle modification.

RESULTS: ECP patients (23 obstructive and two mixed) were enrolled in 2020 during the COVID pandemic. Two hundred and thirty five ECP procedures followed the standard protocol and 121 the 1.5 ECP. There was little or no variation in lung function during the study period. The mean number of mononuclear cells (MNC) per kg administered over time was higher in the 1.5 ECP than in the standard ECP protocol (p = .014). No association was found between respiratory function and MNC infused. Persistent Forced Expiratory Volume in 1 s decline >10% was observed in two patients over the 6 months preceding 1.5 ECP (due to CLAD progression) and in three patients after 1.5 ECP initiation (one for CLAD progression, two for bronchial colonization).

CONCLUSION: Our study shows that respiratory function is maintained over time and is comparable between both ECP strategies in responders. The shift from two to one procedure per cycle may be reasonable in CLAD patients treated by off-line ECP.

PMID:40657687 | DOI:10.1111/trf.18318

Bio Protoc. 2025 Jun 20;15(12):e5341. doi: 10.21769/BioProtoc.5341. eCollection 2025 Jun 20.

ABSTRACT

Epithelial tissues form barriers to the flow of ions, nutrients, waste products, bacteria, and viruses. The conventional electrophysiology measurement of transepithelial resistance (TEER/TER) can quantify epithelial barrier integrity, but does not capture all the electrical behavior of the tissue or provide insight into membrane-specific properties. Electrochemical impedance spectroscopy, in addition to measurement of TER, enables measurement of transepithelial capacitance (TEC) and a ratio of electrical time constants for the tissue, which we term the membrane ratio. This protocol describes how to perform galvanostatic electrochemical impedance spectroscopy on epithelia using commercially available cell culture inserts and chambers, detailing the apparatus, electrical signal, fitting technique, and error quantification. The measurement can be performed in under 1 min on commercially available cell culture inserts and electrophysiology chambers using instrumentation capable of galvanostatic sinusoidal signal processing (4 μA amplitude, 2 Hz to 50 kHz). All fits to the model have less than 10 Ω mean absolute error, revealing repeatable values distinct for each cell type. On representative retinal pigment (n = 3) and bronchiolar epithelial samples (n = 4), TER measurements were 500-667 Ω·cm2 and 955-1,034 Ω·cm2 (within the expected range), TEC measurements were 3.65-4.10 μF/cm2 and 1.07-1.10 μF/cm2, and membrane ratio measurements were 18-22 and 1.9-2.2, respectively. Key features • This protocol requires preexisting experience with culturing epithelial cells (such as Caco-2, RPE, and 16HBE) for a successful outcome. • Builds upon methods by Lewallen et al. [1] and Linz et al. [2], integrating commercial chambers and providing a quantitative estimate of error. • Provides code to run measurement, process data, and report error; requires access to MATLAB software, but no coding experience is necessary. • Allows for repeated measurements on the same sample. Graphical overview Electrochemical impedance spectroscopy measurement involves sending a galvanostatic signal through the electrophysiology chamber and across the epithelial cell monolayer (left) and results in complex impedance data at each frequency. This data is then fit to an electrical circuit model to output transepithelial resistance (TER), transepithelial capacitance (TEC), and membrane ratio (α) (right).

PMID:40657538 | PMC:PMC12254589 | DOI:10.21769/BioProtoc.5341

Indian J Microbiol. 2025 Jun;65(2):1209-1216. doi: 10.1007/s12088-024-01366-8. Epub 2024 Aug 13.

ABSTRACT

A microbial identification method using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF) is an innovative dimension in proteomic analysis. MALDI-ToF mass spectrometry allows not only determine the species and subspecies bacteria, but also determined by proteomic analysis and the corresponding software degree of kinship analyzed strains, which allows this method to be used in epidemiological studies and in comparing strains isolated from patients with chronic infection. The aim of this study was to evaluate the possibility of using protein spectra of microorganisms obtained by MALDI-ToF mass spectrometry as additional microbiological criteria in assessing the course of the infection process caused by Burkholderia cepacia complex among patients with cystic fibrosis. The analysis of protein profiles, which were obtained by using MALDI-ToF mass spectrometry (Bruker Daltonik GmbH, Germany), was performed by using flexAnalisis 3.0 software (Bruker Daltonik GmbH, Germany). Differences in protein profiles of Burkholderia spp. isolates were found depended on the stage of infection of a cystic fibrosis patient with prolonged colonisation of the lower respiratory tract. The protein profiles of Burkholderia spp. isolates that formed a heterogeneous population containing both NCV and SCV morphotypes were also studied. A regular dynamic monitoring and comparison of protein profiles of microbial strains can be useful in forecasting effort of the clinical course of the disease, as well as in assessing of risks of severe infectious complications development.

PMID:40655327 | PMC:PMC12246321 | DOI:10.1007/s12088-024-01366-8

bioRxiv [Preprint]. 2025 May 12:2025.05.07.652658. doi: 10.1101/2025.05.07.652658.

ABSTRACT

Staphylococcus aureus (SA), the most common cystic fibrosis (CF) lung pathogen, is uniquely capable of producing superantigen (SAg) exotoxins, which are the most potent activators of the immune system. Although the proinflammatory roles of SA-SAgs is well-established, their role in the immunopathogenesis of CF lung disease is unexplored. Herein, we demonstrate that 60-80% of pediatric and adult CF SA isolates carried at least one SA-SAg gene, with the former harboring potent SA-SAgs (Staphylococcal enterotoxin A and B) more frequently (30-60%). Biofilms of clinical SA isolates readily produced biologically active SA-SAgs in artificial sputum medium and purified SA-SAgs retained their bioactivity in human CF sputum in vitro. Repeated intratracheal challenge with purified SA-SAgs induced a robust pulmonary inflammatory response in CF mouse models (βENAC and CFGC transgenic mice) expressing HLA-DR3 in a dose-dependent manner, with the low dose favoring a type 2 eosinophilic lung inflammatory response, and a high dose eliciting a type 1 inflammatory response with neutrophilic lung inflammation and higher mortality. In vivo neutralization of IFN-γ also promoted SA-SAg-driven type 2 inflammation. Intratracheal infection with sub-lethal dose of a clinical SA isolate producing SEB, but not the SEB-deficient mutant isogenic SA strain, also elicited an eosinophilic inflammatory response.

PMID:40654878 | PMC:PMC12248047 | DOI:10.1101/2025.05.07.652658

bioRxiv [Preprint]. 2025 May 9:2025.05.08.651222. doi: 10.1101/2025.05.08.651222.

ABSTRACT

Cystic fibrosis (CF) is associated with dysbiosis of the gut microbiome, alterations in intestinal mucus production, aberrant bile acid (BA) metabolism, fat malabsorption, and chronic inflammation. As little is known about BAs in CF, we performed both comprehensive and targeted BA profiling in stool of children with or without CF. Our results reveal that select BA species and metabolites are significantly different between children with CF (cwCF) and healthy controls. There is also a trend towards higher primary cBA and total BA levels for cwCF. Matched bacterial metagenomic analyses showed no change in alpha-diversity between groups in our small cohort, at odds with previous studies, whereas changes in relative abundance of Bacteroides (lower) and E. coli (increased) species is consistent with prior reports. A robust trend was noted toward reduced abundance of bsh gene families (Wilcox test, p = 0.052), a key rate-limiting enzyme required for bacterial synthesis of secondary BAs, in cwCF. Modest changes in both BAs and microbial BA metabolism-related gene abundances may be attributable to small sample sizes, but also suggest likely combination defects in both host and microbial BA metabolic pathways in cwCF. Importantly, although fecal BA profiles from both ferret and mouse CF models showed significant differences from human BA profiles, only the ferret model reproduced significant differences between CF and nonCF animals, highlighting ferrets as a potentially more appropriate model for studying BA in stool in the context of CF. Together, these results provide new insights into CF-related BA dysmetabolism in cwCF, and highlight limitations of CF animal models for BA functional studies.

IMPORTANCE: Changes in the abundance and/or composition of intestinal bile acids (BAs) may contribute to dysbiosis and altered gastrointestinal physiology in CF. Here, we report shifts in select fecal BA classes and species for children with CF (cwCF). Matched metagenomic analysis suggest possible defects in both host intestinal BA absorption and gut microbial BA metabolism. Additional analyses of mouse and ferret CF stool for BA composition suggest great care must be taken when interpreting BA functional studies using these animal models. Together, this work lays technical and conceptual foundations for interrogating BA-microbe interactions in cwCF.

PMID:40654714 | PMC:PMC12248097 | DOI:10.1101/2025.05.08.651222

bioRxiv [Preprint]. 2025 May 8:2025.05.07.652718. doi: 10.1101/2025.05.07.652718.

ABSTRACT

Mycobacterium abscessus is a major human pathogen, mostly infecting people with pre-existing lung conditions such as cystic fibrosis. The production of glycopeptidolipids (GPL) is a major determinant of virulence of this bacterium, with clinical isolates that lack GPL generally exhibiting more aggressive clinical behavior. The current paradigm is that GPL production is abolished in vivo via irreversible, spontaneous mutations taking place as part of in-host evolution. Little is known about the mechanisms or extent to which GPL production may be regulated. Here we describe an unusual TetR-like transcription factor of M. abscessus , MAB_1638, that appears to be a strong positive regulator of the entire GPL biosynthesis and export gene cluster through a combination of direct and indirect mechanisms. The inactivation of mab_1638 abolished GPL production and thus led to stable rough colony morphology, as well as increased virulence in infection models, characteristic of rough, non-GPL-producers. Transcriptome analysis found the mab_1638 mutant had 118 differentially expressed genes, including the GPL locus and a second, recently described GPL-like locus that produces a related glycosylated lipopeptide called GP8L. Chromatin Immunoprecipitation and sequencing revealed a consensus inverted-repeat DNA sequence motif characteristic of genes regulated by mab_1638 . Together, mab_1638 appears to encode a transcription factor required for production of GPL and therefore having a profound effect on virulence traits. We propose naming this gene GPL regulator 1 ( gplR1 ). This finding raises the important possibility that M. abscessus strains appearing smooth in laboratory growth conditions may nonetheless downregulate GPL-cluster genes in other conditions, including in-patient conditions, and thus acquire the phenotypic characteristics of rough strains.

IMPORTANCE: Mycobacterium abscessus is an important human pathogen, causing disease that is difficult to treat. M. abscessus strains have been observed to have two distinct colony morphologies, smooth and rough, which substantially impact clinical presentation. Rough strains are associated with later-stage, more severe disease and are more virulent in animal models. Smooth morphology is conferred by a molecule called glycopeptidolipid in the outer cell envelope, and rough morphology is known to occur when mutations inactivate genes required for glycopeptidolipid biosynthesis. Little is known about the possibility that glycopeptidolipid production could be regulated . Here we have identified a transcription factor that is required for glycopeptidolipid biosynthesis, indicating that glycopeptidolipid production is indeed a regulated process, and raising the important possibility that strains exhibiting smooth morphology in the lab may down-regulated GPL production in the human host and thereby acquire the virulence properties of rough strains.

PMID:40654710 | PMC:PMC12248161 | DOI:10.1101/2025.05.07.652718

Pediatr Transplant. 2025 Aug;29(5):e70139. doi: 10.1111/petr.70139.

ABSTRACT

BACKGROUND: Lung transplantation is the primary surgical therapy for end-stage lung disease in children. Bilateral sequential lung transplantation (BSLT) is the most widely used technique across the United States. En-bloc lung transplantation (EBLT) was put forward as an alternative to avoid the complications associated with bronchial anastomoses in smaller children. There are no multi-institutional reports comparing the outcomes of these two techniques.

METHODS: The United Network for Organ Sharing dataset was queried for patients <= 18 years who underwent bilateral lung transplantation from 2002 to 2021. Patients were divided into two groups based on surgical technique: EBLT and BSLT. Demographic and clinical characteristics were compared, along with follow-up survival data. The primary outcome of interest was freedom from death or re-transplantation. Subgroup analysis was performed for patients aged <=5 years.

RESULTS: 919 children received lung transplants during the study period. The EBLT technique was utilized in 80 (8.7%) transplants. EBLT patients were younger (9.5 vs. 15 years, p = 0.0001) and more likely to be on mechanical ventilation (33.8 vs. 17.3%, p = 0.0003). EBLT had a lower proportion of cystic fibrosis (37.5 vs. 55.5%, p < 0.0001) as the primary diagnosis. There was no difference in freedom from death or re-transplantation (p = 0.81) or early rejection (17.5 vs. 27.1%, p = 0.17) between the two groups. EBLT patients had less airway dehiscence (0.0 vs. 1.2%, p = 0.006) and less bronchiolitis obliterans (36.3 vs. 65.0%, p = 0.001) during the period of follow-up. On multivariable analysis, surgical technique was not an independent risk factor for survival (HR 0.99 [CI 0.68-1.38], p = 0.92). For patients aged ≤ 5 years, there was no difference in survival between EBLT and BSLT (p = 0.97).

CONCLUSIONS: EBLT is associated with less airway dehiscence and bronchiolitis obliterans than BSLT in children. There is no difference in freedom from death or re-transplantation between the groups.

PMID:40653619 | DOI:10.1111/petr.70139

Sci Rep. 2025 Jul 13;15(1):25328. doi: 10.1038/s41598-025-10519-8.

ABSTRACT

Pseudomonas aeruginosa commonly infects immunocompromised patients, including those with cystic fibrosis (CF). These infections are difficult to treat due to a variety of factors including the ability of Pseudomonas aeruginosa to resist to antibiotic treatment in part due to formation of biofilms. D-amino acids have known biofilm-disruption and antibacterial properties in some bacteria including P. aeruginosa. However, this treatment remains underexplored especially for inhibiting biofilm biomass production under CF environments. We explore the effects of six individual D-amino acids (alanine, aspartic acid, tyrosine, glutamic acid, serine, and proline) on the quorum sensing signaling and biofilm biomass production of two strains: PAO1 and the CF isolate FRD1. The D-amino acid causing the most significant decrease in biofilm mass and a decrease in quorum sensing molecules was D-aspartic acid. Meanwhile D-glutamic acid and D-serine had the opposite effects with an increase in biofilm mass and increase in quorum sensing molecule abundance. D-proline also showed a decrease in quorum sensing signaling with a decrease in biofilm biomass. P. aeruginosa had a lower or delayed quorum sensing response in the presence of D-aspartic acid and the absence of its L- counterpart at 48 h, a potential therapeutic route to explore.

PMID:40653503 | DOI:10.1038/s41598-025-10519-8

Respir Med. 2025 Jul 11:108251. doi: 10.1016/j.rmed.2025.108251. Online ahead of print.

NO ABSTRACT

PMID:40653279 | DOI:10.1016/j.rmed.2025.108251