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

Int J Pediatr Otorhinolaryngol. 2025 Jan 24;189:112238. doi: 10.1016/j.ijporl.2025.112238. Online ahead of print.

ABSTRACT

PURPOSE: Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population. Otolaryngological manifestations pose a significant impact on the quality of life of children with CF. The primary aim of this review is to provide a state of the art update of current literature on the otolaryngological manifestations of CF in children.

METHODS: We systematically reviewed the PubMed, Cochrane Library, Embase and Web of Science databases, for prospective studies including pediatric patients with cystic fibrosis, reporting on otolaryngological manifestations. After assessment of the risk of bias and quality of the included studies, data were extracted.

RESULTS: The search retrieved 6745 unique items after duplicate removal. After three selection rounds and quality assessment, 38 articles were ultimately retained for data extraction. The total number of participants in the studies was 1981. Most studies were prospective cohort studies (n = 28). The articles were divided into six groups (ear/speech disorders - aminoglycoside ototoxicity (n = 10); otolaryngology-related quality of life (n = 5); nasal and paranasal sinuses (n = 11); sleep disorders (n = 3); paranasal sinuses imaging (n = 5); other (n = 4)).

CONCLUSION: The most common otolaryngological manifestation of children with CF is chronic rhinosinusitis, but CF can have other otolaryngological-related pathologies such as hearing loss, middle ear problems, sleep apnea syndrome, and decreased smell and/or taste functions. We found a considerable gap in the literature if we would draw evidence-based conclusions on diagnosis and management of otolaryngological manifestations in children with CF.

PMID:39879870 | DOI:10.1016/j.ijporl.2025.112238

Redox Biol. 2025 Jan 24;80:103513. doi: 10.1016/j.redox.2025.103513. Online ahead of print.

ABSTRACT

Repeated use of nitroglycerin results in a loss of its vasodilatory efficacy which limits its clinical use for the treatment of angina pectoris. This tolerance phenomenon is a defining characteristic of all compounds classified as nitrodilators, which includes NTG as well as S-nitrosothiols and dinitrosyl iron complexes. These compounds vasodilate via activation of soluble guanylate cyclase, although they do not release requisite amounts of free nitric oxide (NO) and some do not even cross the plasma membrane. Here we demonstrate that nitrodilators cause vasodilation via mobilization of NO moiety from a nitrodilator-activated NO store (NANOS) pre-formed in the vascular smooth muscle cell, similar to the mechanism by which UV light is also known to cause vasodilation and tolerance. Intraperitoneal nitrite prevented NTG tolerance in coronary arteries of rats that received NTG transdermal patches for 4 days, and potentiated NTG- and GSNO- mediated mesenteric vasodilation in intact rats. Consistent with the incorporation of nitrite into the depletable NANOS, incubation of arteries with 15N-nitrite resulted in the accumulation of high molecular weight 15N-NO-containing compounds in arteries, and subsequent exposure to NTG, GSNO, or UV light resulted in efflux of 15N-NO species. In addition, H2O2 and metal/metalloproteins synergistically facilitated NO release from nitrite, while the oxidative stress associated with inflammation and nitrite synergistically potentiated the nitrodilator-mediated vasodilation. In conclusion, NTG mediates vasodilation via activation of a depletable intracellular store of NO that can be replenished by nitrite, thereby preventing tolerance.

PMID:39879735 | DOI:10.1016/j.redox.2025.103513

J Bras Pneumol. 2025 Jan 27;51(1):e20240258. doi: 10.36416/1806-3756/e20240258.

NO ABSTRACT

PMID:39879516 | DOI:10.36416/1806-3756/e20240258

Intern Med J. 2025 Jan 29. doi: 10.1111/imj.16641. Online ahead of print.

ABSTRACT

BACKGROUND: Return-to-work (RTW) following lung transplant has been associated with increased quality of life, but little is known regarding the rates of and barriers to this in the Australian population.

AIMS: We aimed to describe, characterise and determine predictors of return to work and social participation in Australian lung transplant recipients. We also sought to explore the relationship between return to work and quality of life.

METHODS: We conducted a cross-sectional questionnaire-based study at the Alfred Hospital, Melbourne between October 2018 and August 2019. The questionnaire evaluated demographics, transplant history, respiratory parameters, employment history and social integration prior to and after lung transplantation.

RESULTS: A total of 172 lung transplant recipients were included for analysis. The population was mostly male (56.5%), median age 61 years (interquartile range (IQR) 49.8-67.0) and median time from transplant 4 years (IQR 2-7). A total of 19.2% of patients were working at time of transplant, with 35.5% working after transplant representing an increase in workforce engagement of 84.8% (P < 0.001). A total of 96% of those who returned to work reported an improvement in quality of life. Median time to RTW after transplant was 180 days (IQR 90-360). Multivariable analysis demonstrated an increased rate of RTW in younger recipients (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.89-0.99, adjusted P = 0.029), at greater length of time after transplant (OR 1.09, 95% CI 0.99-1.19, P = 0.084), among those working at the time of transplant (OR 9.55, 95% CI 2.70-33.75, P < 0.001) and with higher socioeconomic status (OR 1.02, 95% CI 1.01-1.04, P = 0.009). Recipients with cystic fibrosis were more likely to RTW (65.8%) than those with other underlying conditions.

CONCLUSIONS: RTW should be encouraged in lung transplant recipients. Targeted supports and resources aimed at younger recipients may result in greater workforce engagement and overall outcomes after transplant.

PMID:39877944 | DOI:10.1111/imj.16641

Cureus. 2024 Dec 28;16(12):e76529. doi: 10.7759/cureus.76529. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Children who suffer from long-term illnesses, including asthma, cystic fibrosis, diabetes, or epilepsy, sometimes struggle to manage their ailments, which affects their quality of life and how often they use healthcare services.

OBJECTIVE: This study aimed to explore comprehensive long-term management strategies for children with asthma, cystic fibrosis, diabetes, and epilepsy, with a focus on enhancing quality of life and reducing hospital admissions.

METHODOLOGY: A prospective cohort research was conducted involving 480 children, divided into four groups: 120 children with asthma, 120 children with cystic fibrosis, 120 children with diabetes, and 120 children with epilepsy. Participants were evaluated at baseline and at several follow-ups (3, 6, 12, and 24 months) across a 24-month period. Structured surveys, including questions on treatment adherence and quality of life metrics, as well as checks of medical records to monitor hospital admissions, were used to gather data. To investigate changes in hospital admission rates and quality of life scores over time, statistical analyses were performed, including paired t-tests. Statistical significance was defined as a p-value of less than 0.05.

RESULTS: Quality of life scores improved significantly for all groups, with asthma patients demonstrating the most significant increase of 12.53 ± 3.51 points, rising from a baseline score of 62.54 ± 14.03 to 75.07 ± 10.52 (p < 0.001). Hospital admissions also declined substantially, particularly in the asthma group, which reduced from 4.51 ± 2.07 to 2.06 ± 1.37 (p < 0.001). High adherence rates were observed among patients, with 85 (70.83%) in asthma, 90 (75.00%) in cystic fibrosis, 95 (79.17%) in diabetes, and 92 (76.67%) in epilepsy. Additionally, patient satisfaction scores were notably high, averaging 78.02 ± 10.07 in asthma, 80.03 ± 9.52 in cystic fibrosis, 82.21 ± 8.05 in diabetes, and 79.15 ± 9.03 in epilepsy across the different disease categories.

CONCLUSION: Children with chronic illnesses have a much higher quality of life and fewer hospital admissions when family engagement techniques and technology-driven monitoring are used.

PMID:39877791 | PMC:PMC11772561 | DOI:10.7759/cureus.76529

Open Forum Infect Dis. 2025 Jan 8;12(1):ofaf001. doi: 10.1093/ofid/ofaf001. eCollection 2025 Jan.

ABSTRACT

BACKGROUND: Improved diagnostic testing (DT) of infections may optimize outcomes for solid organ transplant recipients (SOTR), but a comprehensive analysis is lacking.

METHODS: We conducted a systematic literature review across multiple databases, including EMBASE and MEDLINE(R), of studies published between 1 January 2012-11 June 2022, to examine the evidence behind DT in SOTR. Eligibility criteria included the use of conventional diagnostic methods (culture, biomarkers, directed-polymerase chain reaction [PCR]) or advanced molecular diagnostics (broad-range PCR, metagenomics) to diagnose infections in hospitalized SOTR. Bias was assessed using tools such as the Cochrane Handbook and PRISMA 2020.

RESULTS: Of 2362 studies, 72 were eligible and evaluated heterogeneous SOT populations, infections, biospecimens, DT, and outcomes. All studies exhibited bias, mainly in reporting quality. Median study sample size was 102 (range, 11-1307). Culture was the most common DT studied (N = 45 studies, 62.5%), with positive results in a median of 27.7% (range, 0%-88.3%). Biomarkers, PCR, and metagenomics were evaluated in 7, 19, and 3 studies, respectively; only 6 reported sensitivity, specificity, and positive/negative predictive values. Directed-PCR performed well for targeted pathogens, but only 1 study evaluated broad-range PCR. Metagenomics approaches detected numerous organisms but required clinical adjudication, with too few studies (N = 3) to draw conclusions. Turnaround time was shorter for PCR/metagenomics than conventional diagnostic methods (N = 4 studies, 5.6%). Only 6 studies reported the impact of DT on outcomes like antimicrobial use and length of stay.

CONCLUSIONS: We identified considerable evidence gaps in infection-related DT among SOT, particularly molecular DT, highlighting the need for further research.

PMID:39877399 | PMC:PMC11773193 | DOI:10.1093/ofid/ofaf001

Biofilm. 2025 Jan 6;9:100250. doi: 10.1016/j.bioflm.2024.100250. eCollection 2025 Jun.

ABSTRACT

Bacterial biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa pose significant challenges in treating cystic fibrosis (CF) airway infections due to their resistance to antibiotics. New therapeutic approaches are urgently needed to treat these chronic infections. This study aimed to investigate the antibiofilm potential of various plant extracts, specifically targeting mucoid and small colony variants of P. aeruginosa and S. aureus and strains. Moreover, it aimed to gain insights into the mechanisms of action and the potential phytochemicals responsible for antibiofilm activity. Solid-liquid extractions were performed on seven biomasses using water and ethanol (70 and 96 %) under controlled conditions, resulting in 21 distinct plant extracts. These extracts were evaluated for extraction yield, antioxidant activity, phenolic content, chemical composition by HPLC-TOF-MS, and antibiofilm activity using a 96-well plate assay, followed by crystal violet staining, bacterial adhesion assessment, and brightfield microscopy. Our findings revealed that aqueous extracts exhibited the highest inhibition of biofilm formation, with cinnamon bark and moringa seeds showing strong antibiofilm activity against both bacterial species. Brightfield microscopy confirmed that these extracts effectively inhibited biofilm formation. Chemical analysis identified key bioactive compounds, including moringin, benzaldehyde, coumarin, and quinic acid, which likely contribute to the observed antibiofilm effects. Recognizing that the antibiofilm properties of moringin, a common compound in both moringa seed and cinnamon bark extracts, remain underexplored, we conducted potential target identification via PharmMapper and molecular docking analyses to provide a foundation for future research. Computational analyses indicated that moringin might inhibit aspartate-semialdehyde dehydrogenase in P. aeruginosa and potentially interact with an unknown target in S. aureus. In conclusion, moringa seed and cinnamon bark extracts demonstrated significant potential for developing new therapies targeting biofilm-associated infections in CF. Further studies are needed to validate the computational predictions, identify the bacterial targets, and elucidate the precise mechanisms behind moringin's antibiofilm activity, which is likely the potential key contributor to the observed activity of the moringa and cinnamon bark extracts.

PMID:39877233 | PMC:PMC11772965 | DOI:10.1016/j.bioflm.2024.100250

Chron Respir Dis. 2025 Jan-Dec;22:14799731241249476. doi: 10.1177/14799731241249476.

ABSTRACT

Background: The use of non-invasive ventilation (NIV) in patients with advanced cystic fibrosis (CF) has increased in recent years. Research evidence supports its clinical benefits, but less is known about the patients' experience of its long-term use in a domiciliary setting.Objective: To investigate patients' lived experience of using long-term domiciliary NIV.Methods: Semi-structured, qualitative interviews were conducted with adults with CF using long-term domiciliary NIV for respiratory failure. The data collected were subject to thematic analysis.Results: Nine adults (6 female), 5 of whom were awaiting lung transplantation, with a mean age of 39 years and mean FEV1 per cent predicted of 28%, were recruited. Data analysis revealed 2 themes: gratitude, and determination despite challenges. Patients identified some troubling side effects from NIV but were grateful for its symptomatic relief and were determined to continue using it to improve their quality of life.Conclusions: Participants reported experiences of NIV to be generally positive in terms of symptom relief and quality of life. These findings provide an initial insight into patients' experience of NIV and have the potential to help guide and improve care.

PMID:39876815 | DOI:10.1177/14799731241249476

Health Expect. 2025 Feb;28(1):e70156. doi: 10.1111/hex.70156.

ABSTRACT

BACKGROUND: Lung transplantation improves survival and quality of life in young people with end-stage lung disease. Few studies have investigated the clinical care experiences of young people after lung transplantation.

DESIGN: This qualitative study aimed to explore the experiences of young people who underwent lung transplantation. Semi-structured interviews were conducted with 16 lung transplant recipients (< 25 years at transplant). Interviews were analysed to identify themes and categorize and describe the experience of young lung transplant recipients.

RESULTS: The themes that emerged were (1) Hope and spectre: The transplant dilemma; (2) Information delivery and comprehension; (3) Independence and navigating care; and (4) Continuity and youth-appropriate care. Findings suggest that young people have distinct care needs that consider the many parallel life transitions that occur in addition to transplantation. They value consistent and familiar teams, which nurture autonomy and independence in the context of post-transplant survivorship and highlight the importance of feeling that they can relate to the healthcare process.

CONCLUSION: The results highlight key areas where adolescent lung transplant recipients can be supported by clinicians, enabling the development of youth-friendly services that cater to this group's healthcare and psychosocial needs.

PATIENT OR PUBLIC CONTRIBUTION: Sixteen lung transplant recipients participated in the study by completing a semi-structured interview. Two additional lung transplant recipients who received lung transplants as adolescents and one parent of an adolescent lung transplant recipient participated in a Project Advisory Group (PAG) with six clinicians representing paediatric, adolescent, and adult healthcare experience. They provided advice on research design including the development and revision of the interview guide and recruitment methods. They additionally provided feedback on the preliminary findings and outline of the manuscript. A summary of results was presented to the PAG who in conjunction with the writing group developed a list of recommendations based on the themes identified and the tenets of youth-appropriate care as set out by the World Health Organization. One lung transplant recipient was an author on the manuscript contributing to its writing and review before submission. The clinicians who participated in the PAG did not have direct healthcare relationships with the study participants.

PMID:39876587 | DOI:10.1111/hex.70156

Pediatr Pulmonol. 2025 Jan;60(1):e27498. doi: 10.1002/ppul.27498.

NO ABSTRACT

PMID:39876081 | DOI:10.1002/ppul.27498

Stem Cell Res Ther. 2025 Jan 29;16(1):29. doi: 10.1186/s13287-025-04152-5.

ABSTRACT

Chronic pulmonary diseases pose a prominent health threat globally owing to their intricate pathogenesis and lack of effective reversal therapies. Nowadays, lung transplantation stands out as a feasible treatment option for patients with end-stage lung disease. Unfortunately, the use of this this option is limited by donor organ shortage and severe immunological rejection reactions. Recently, airway basal stem cells (BSCs) have emerged as a novel therapeutic strategy in pulmonary regenerative medicine because of their substantial potential in repairing lung structure and function. Airway BSCs, which are strongly capable of self-renewal and multi-lineage differentiation, can effectively attenuate airway epithelial injury caused by environmental factors or genetic disorders, such as cystic fibrosis. This review comprehensively explores the efficacy and action mechanisms of airway BSCs across various lung disease models and describes potential strategies for inducing pluripotent stem cells to differentiate into pulmonary epithelial lineages on the basis of the original research findings. Additionally, the review also discusses the technical and biological challenges in translating these research findings into clinical applications and offers prospective views on future research directions, therefore broadening the landscape of pulmonary regenerative medicine.

PMID:39876014 | DOI:10.1186/s13287-025-04152-5

JMIR Res Protoc. 2025 Jan 28;14:e62931. doi: 10.2196/62931.

ABSTRACT

BACKGROUND: Diabetes affects half of the patients with cystic fibrosis who are aged 30 years and older. Diabetes progresses asymptomatically over a long period of time. Two treatment options are possible: start insulin as soon as cystic fibrosis diagnosis is made with the additional constraints of cystic fibrosis or wait while monitoring the patient's clinical condition and start insulin when diabetes symptoms develop and therefore later. This situation is particularly well suited to shared decision-making (SDM) between the physician (health care team) and patient/relatives.

OBJECTIVE: The aim of this study was to perform qualitative and quantitative analyses for evaluating the outcomes and experience of SDM implementation between the physician/health care team trained for SDM and patients/their relatives for cystic fibrosis-related diabetes.

METHODS: A quasi-experimental with a comparison study will be developed. Three cystic fibrosis reference centers (CFRCs) will be trained in SDM by using a web-based training, including a validated decision aid and coaching for physicians and the medical team. Two control CFRCs will maintain their usual practices. A qualitative analysis through observation of consultations, individual semistructured interviews with patients, and focus groups in CFRCs will be conducted based on a thematic content analysis. Questionnaires related to decision-making and experience of decision-making with and without SDM implementation will be administered to patients and physicians.

RESULTS: Forty patients will be included (8 patients in each center), that is, 60 consultation observations (2 consultations per patient in the intervention groups given the modalities of the SDM process) will be conducted in 2025. Eight focus groups will be conducted in the 5 centers (2 groups in each intervention CFRC and 1 group in each control CFRC). This qualitative corpus plus responses to the patient and physician questionnaires will make it possible to know whether the practice of SDM in CFRCs is increased by an implementation strategy and to analyze the experience of patients and their relatives regarding decision-making modalities. Analysis of the outcomes and experience of the implementation of SDM are of importance to identify the facilitators and barriers to SDM from patients' and CFRCs' point of views.

CONCLUSIONS: Our study will give us keys to adapt, improve, and disseminate SDM more widely in the context of cystic fibrosis therapy. SDM could thus be used in routine clinical practice in CFRCs at the national level.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04891159; https://clinicaltrials.gov/study/NCT04891159?id=NCT04891159.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/62931.

PMID:39874570 | DOI:10.2196/62931

Eur Clin Respir J. 2025 Jan 24;12(1):2458341. doi: 10.1080/20018525.2025.2458341. eCollection 2025.

ABSTRACT

Therapeutic drug monitoring (TDM) of elexacaftor/tezacaftor/ivacaftor (ETI) remains challenging due to a lack of clarity around the parameters that govern ETI plasma concentrations, whilst the use of concomitant CYP3A inducers rifabutin and rifampicin is not recommended. We present the complexities of TDM for ETI performed in a person with cystic fibrosis and refractory Mycobacterium abscessus pulmonary disease. Utilising National Association of Testing Authorities (NATA) accredited assays and target considerations published by the Therapeutic Goods Administration (TGA), Australia, ETI plasma concentration variability was monitored over the course of an acute admission with added complexity from an antibiotic regimen including rifabutin, a moderate cytochrome P450 3A (CYP3A) inducer, and clofazimine, a mild CYP3A inhibitor. This case highlights the challenges surrounding ETI TDM in the context of acute severe illness, malnutrition, chronic infection, and drug-to-drug interactions. The marked clinical improvement seen, alongside sustained ETI plasma concentrations and suppressed sweat chloride levels on serial testing, provided reassurance of the use of ETI and rifabutin concomitantly in this case, and highlights the potential utility of TDM in helping guide clinical practice. Though a current barrier to the application of TDM includes ETI only being available as a fixed dose combination.

PMID:39872799 | PMC:PMC11770854 | DOI:10.1080/20018525.2025.2458341

ERJ Open Res. 2025 Jan 27;11(1):00793-2024. doi: 10.1183/23120541.00793-2024. eCollection 2025 Jan.

ABSTRACT

Identifying mucous plugs by chest CT should be considered carefully because it is potentially a treatable trait https://bit.ly/4gyJHFW.

PMID:39872389 | PMC:PMC11770761 | DOI:10.1183/23120541.00793-2024

ERJ Open Res. 2025 Jan 27;11(1):00386-2024. doi: 10.1183/23120541.00386-2024. eCollection 2025 Jan.

ABSTRACT

pwCF carrying the Q359K/T360K variant may have significant clinical benefit from treatment with ETI that may exceed improvements observed with TI treatment. These data support routine clinical use of ETI in this rare patient group. https://bit.ly/45DjFw9.

PMID:39872382 | PMC:PMC11770694 | DOI:10.1183/23120541.00386-2024

J Mater Chem B. 2025 Jan 28. doi: 10.1039/d4tb02675f. Online ahead of print.

ABSTRACT

The reason why certain bacteria, e.g., Pseudomonas aeruginosa (PA), produce acetylated alginate (Alg) in their biofilms remains one of the most intriguing facts in microbiology. Being the main structural component of the secreted biofilm, like the one formed in the lungs of cystic fibrosis (CF) patients, Alg plays a crucial role in protecting the bacteria from environmental stress and potential threats. Nonetheless, to investigate the PA biofilm environment and its lack of susceptibility to antibiotic treatment, the currently developed in vitro biofilm models use native seaweed Alg, which is a non-acetylated Alg. The role of the acetyl side group on the backbone of bacterial Alg has never been elucidated, and the transposition of experimental results obtained from such systems to clinical conditions (e.g., to treat CF-infection) may be hazardous. We systematically investigated the influence of acetylation on the physico-chemical and mechanical properties of Alg in solution and Ca2+-crosslinked hydrogels. Furthermore, we assessed how the acetylation influenced the interaction of Alg with tobramycin, a common aminoglycoside antibiotic for PA. Our study revealed that the degree of acetylation directly impacts the viscosity and Young's Modulus of Alg in a pH-dependent manner. Acetylation increased the mesh size in biofilm-like Alg hydrogels, directly influencing antibiotic penetration. Our results provide essential insights to create more clinically relevant in vitro infection models to test the efficacy of new drugs or to better understand the 3D microenvironment of PA biofilms.

PMID:39871625 | DOI:10.1039/d4tb02675f