Pediatr Pulmonol. 2024 Oct 23. doi: 10.1002/ppul.27326. Online ahead of print.

ABSTRACT

BACKGROUND: The cystic fibrosis (CF) Responsibility. Independence. Self-care. Education. (R.I.S.E.) program was developed to provide assessment and education, supporting transition readiness for people with cystic fibrosis (pwCF). Lack of integration within electronic health records (EHR) was a barrier to implementation of CF R.I.S.E. University of Michigan was able to integrate CF R.I.S.E. into EHR.

AIM: To improve implementation and EHR documentation of CF R.I.S.E. module completion by pwCF across two (CF) programs from baseline (10.5%) to 75% per month in 6 months (January through June 2023).

METHODS: Two CF programs utilized quality improvement (QI) methods and tools and ad hoc support by a CF Learning Network (QI) specialist. Eligibility included pwCF ≥16 years old seen in CF clinics who accepted CF R.I.S.E.

PARTICIPATION: Beginning January 2, 2023, programs met in biweekly, virtual meetings to discuss implementation. Deidentified data were collected monthly tracking modules completed by pwCF and number of team members engaging with CF R.I.S.E. and documenting in EHR. Data timelines were baseline (November-December 2022), project period (January-June 2023), and post-project (July-December 2023).

RESULTS: Completion rates increased from baseline (10.5%) to 48% (range 33% to 81%) through December 2023. During the project, an average 7.7 team members completed an average 19.2 modules per month. Post-project, an average 8 team members completed an average 16.5 modules per month.

CONCLUSIONS: This collaboration demonstrated how utilization of EHR allowed for successful CF R.I.S.E. improvement at both programs. Shared software utilization and QI initiatives may be a way to facilitate timely dissemination of best practices through learning health systems.

PMID:39441068 | DOI:10.1002/ppul.27326

J Investig Allergol Clin Immunol. 2024 Oct;34(5):344-346. doi: 10.18176/jiaci.0982.

NO ABSTRACT

PMID:39441049 | DOI:10.18176/jiaci.0982

Microbiol Spectr. 2024 Oct 23:e0105624. doi: 10.1128/spectrum.01056-24. Online ahead of print.

ABSTRACT

Mycobacterium abscessus is an emerging opportunistic pathogen affecting patients with chronic lung diseases, primarily cystic fibrosis (CF), or those under immunosuppression. Hence, investigations into the epidemiology and transmission of M. abscessus and accurate antibiotic susceptibility data are essential for the effective treatment of infections caused by this pathogen. This retrospective nationwide study included all clinical M. abscessus isolates (n = 59) from 29 patients diagnosed in the Czech Republic and Slovakia between 2018 and 2023. Whole genome sequencing (WGS) was performed to identify clusters and classify isolates into predominant circulating clones (DCC). Subspecies identification of unique isolates showed subspecies abscessus as the most prevalent (69.0%). The results of drug-susceptibility testing showed that 65.5% of all isolates were resistant to at least three antibiotics tested. CF patients under 24 years of age were the most at-risk group for M. abscessus infection. WGS identified seven clusters (including two cross-border) comprising CF and non-CF patients with a total clustering rate of 48.3%. One cluster involved patients infected with subspecies massiliense strains differing by 0 single nucleotide polymorphisms hospitalized in the same center. Furthermore, we identified representatives of all major DCCs. This study revealed predominant Mycobacterium abscessus complex clones circulating in the Czech Republic and Slovakia. The results show the high discriminatory power of WGS in the molecular epidemiology of M. abscessus and provide supporting evidence of direct or indirect cross-transmission of subspecies massiliense among both CF and non-CF patients.

IMPORTANCE: This study highlights the importance of understanding Mycobacterium abscessus transmission because it poses a growing threat to vulnerable populations, especially young cystic fibrosis patients. Investigating how it spreads and which antibiotics work best is crucial for effective treatment. This research used whole genome sequencing to track M. abscessus and found evidence of potential transmission between patients, including across borders. The findings suggest that dominant strains are circulating and some patients may be infected through direct or indirect contact. This knowledge can inform infection control and treatment strategies.

PMID:39440987 | DOI:10.1128/spectrum.01056-24

Microbiol Spectr. 2024 Oct 23:e0110024. doi: 10.1128/spectrum.01100-24. Online ahead of print.

ABSTRACT

Thirty-nine clinical isolates of Pseudomonas aeruginosa collected from 11 cystic fibrosis (CF) patients at two CF attention centers over 10 years were subjected to whole genome sequencing (WGS). Phenotypic tests (i.e., elastase, motility, biofilm, growth rate, and antibiotic susceptibility) were performed to correlate results. A single strain of P. aeruginosa was found to persist over time in longitudinal isolates. No transmission between patients or centers was observed. A tendency to lack genes related to pyoverdine, flagellum, pili, and O-antigen was observed, whereas those related to biofilm, phenazine, and pyochelin were conserved among isolates. In a patient with a 10-year follow-up, a single strain of P. aeruginosa persisted and showed a gradual decrease in elastase activity and growth rate, demonstrating an adaptive phenotype.IMPORTANCEThis study investigates the genomic and phenotypic characteristics of Pseudomonas aeruginosa isolates from Mexican cystic fibrosis (CF) patients, an underrepresented group in CF research. To our knowledge, it is the first to use whole genome sequencing (WGS) to study longitudinally collected P. aeruginosa isolates from this population, evaluating both genomic features and clonal relationships. Remarkably, the study includes samples from one patient over 10 years, offering an extended observation time compared to existing literature. Unlike similar studies, which often lack phenotypic testing, this research incorporates various virulence-related phenotypic assays, enhancing our understanding of gene-to-phenotype correlations. Two potential mechanisms for the loss of elastolytic activity were identified. Furthermore, we conduct an in-depth mobilome analysis, an area that remains largely unexplored in CF contexts. Whole genome sequencing data are publicly available through the NCBI SRA database, facilitating further re-analysis for studies on P. aeruginosa in CF, as well as epidemiological and population structure research.

PMID:39440985 | DOI:10.1128/spectrum.01100-24

Adv Healthc Mater. 2024 Oct 23:e2401918. doi: 10.1002/adhm.202401918. Online ahead of print.

ABSTRACT

Ionizable lipid nanoparticles (LNPs) are pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid-based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs. Here, a mechanical oscillation (frequency: 65 Hz) is utilized to prompt the LNP-mediated endosomal escape. The results reveal this mechanical oscillation can induce the combination and fusion between LNPs with opposite surface charges, enhance endosomal escape of mRNA, and increase the transfection efficiency of mRNA. Additionally, cell viability remains high at 99.3% after treatment with oscillation, which is comparable to that of untreated cells. Furthermore, there is no obvious damage to mitochondrial membrane potential and Golgi apparatus integrity. Thus, this work presents a user-friendly and safe approach to enhancing endosomal escape of mRNA and boosting gene expression. As a result, this work can be potentially utilized in both research and clinical fields to facilitate LNP-based delivery by enabling more effective release of LNP-encapsulated cargos from endosomes.

PMID:39440644 | DOI:10.1002/adhm.202401918

Cureus. 2024 Oct 22;16(10):e72144. doi: 10.7759/cureus.72144. eCollection 2024 Oct.

ABSTRACT

Healthcare delivery is made more convenient and effective via telemedicine, which enables physicians to conduct virtual consultations and evaluations with pediatric patients. The purpose of this systematic review was to evaluate the efficacy of telemedicine as compared to physical appointments in the pediatric population. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search for the available literature using pre-specified inclusion and exclusion criteria. These databases provided 968 relevant research articles, which Endnote software screened for duplicates. Fourteen studies were considered relevant for full-text evaluation. After complete text evaluation, only 11 of these articles were found to be relevant. The Newcastle-Ottawa Scale (NOS) was used for the risk of bias assessment of all included studies. Eleven articles in all satisfied the requirements for inclusion and were added to the review. Every study was classified as either a cluster randomized trial (27%) or a randomized controlled trial (RCT) (73%). There were between 22 and 400 participants in each trial. Medical conditions evaluated included obesity (27%), mental health disorders (9%), asthma (18%), otitis media (9%), skin disorders (9%), type 1 diabetes (9%), attention deficit hyperactivity disorder (ADHD) (9%), and pancreatic insufficiency associated with cystic fibrosis (1/11). Telemedicine strategies employed included telemedicine-based screening visits (9%), smartphone-based therapies (27%), phone counseling (18%), and videoconferencing visits between patients and doctors (45%). The outcomes of the telemedicine procedures in every included study were on par with or superior to those of the control groups. Medication adherence, appointment completion rates, life satisfaction, symptom management, and disease progression were all outcomes associated with these findings. Although more research is needed, the evidence from this review suggests that telemedicine services for the general public and pediatric care are comparable to or better than in-person services. Patients, healthcare professionals, and caregivers may benefit from using both telemedicine services and traditional in-person healthcare services. To maximize the potential of telemedicine, future research should focus on improving patients' access to care, increasing the cost-effectiveness of telemedicine services, and eliminating barriers to telemedicine use.

PMID:39440160 | PMC:PMC11495680 | DOI:10.7759/cureus.72144

Front Pharmacol. 2024 Oct 8;15:1476331. doi: 10.3389/fphar.2024.1476331. eCollection 2024.

ABSTRACT

Cystic fibrosis is a life-threatening disease that is caused by mutations in CFTR, a gene which encodes an ion channel that supports proper function of several epithelial tissues, most critically the lung. Without CFTR, airway barrier mechanisms are impaired, allowing for chronic, recurrent infections that result in airway remodeling and deterioration of lung structure and function. Small molecule modulators can rescue existing, defective CFTR protein; however, they still leave a subset of people with CF with no current disease modifying treatments, aside from lung transplantation. Gene therapy directed to the lung is a promising strategy to modify CF disease in the organ most associated with morbidity and mortality. It is accomplished through delivery of a CFTR transgene with an airway permissive vector. Despite more than three decades of research in this area, a lung directed gene therapy has yet to be realized. There is hope that with improved delivery vectors, sufficient transduction of airway cells can achieve therapeutic levels of functional CFTR. In order to do this, preclinical programs need to meet a certain level of CFTR protein expression in vitro and in vivo through improved transduction, particularly in relevant airway cell types. Furthermore, clinical programs must be designed with sensitive methods to detect CFTR expression and function as well as methods to measure meaningful endpoints for lung structure, function and disease. Here, we discuss the current understanding of how much and where CFTR needs to be expressed, the most advanced vectors for CFTR delivery and clinical considerations for detecting CFTR protein and function in different patient subsets.

PMID:39439894 | PMC:PMC11493704 | DOI:10.3389/fphar.2024.1476331

Infect Control Hosp Epidemiol. 2024 Oct 23:1-6. doi: 10.1017/ice.2024.102. Online ahead of print.

ABSTRACT

BACKGROUND: Infection control guidelines for cystic fibrosis (CF) stress cleaning of environmental surfaces and patientcare equipment in CF clinics. This multicenter study measured cleanliness of frequently touched surfaces in CF clinics using an ATP bioluminescence assay to assess the effectiveness of cleaning/disinfection and the impact of feedback.

METHODS: Eight surfaces were tested across 19 clinics (10 pediatric, 9 adult) over 5 rounds of testing. Rounds 1 and 2 served as uncleaned baseline, and Round 3 occurring after routine cleaning. Rounds 4 and 5 were performed after feedback provided to staff and measured after cleaning. Pass rates defined as <250 relative light units were the primary outcome.

RESULTS: Of the 750 tests performed, 72% of surfaces passed at baseline, and 79%, 83%, and 85% of surfaces passed in Rounds 3, 4, and 5, respectively. The overall pass-rate was significantly higher in adult compared to pediatric clinics (86% vs 71%; P < 0.001). In pediatric clinics, blood pressure equipment and computer keyboards in the pulmonary function lab consistently passed, but the exam room patient/visitor chairs consistently failed in all rounds. In adult clinics blood pressure equipment, keyboards in exam rooms and exam tables passed in all rounds and no surface consistently failed.

CONCLUSION: We demonstrate the feasibility of an ATP bioluminescence assay to measure cleanliness of patient care equipment and surfaces in CF clinics. Pass rates improved after cleaning and feedback for certain surfaces. We found that surfaces are more challenging to keep clean in clinics taking care of younger patients.

PMID:39439036 | DOI:10.1017/ice.2024.102

Am J Physiol Lung Cell Mol Physiol. 2024 Oct 22. doi: 10.1152/ajplung.00272.2024. Online ahead of print.

ABSTRACT

The combination of elexacaftor/tezacaftor/ivacaftor (ETI, Trikafta) reverses the primary defect in Cystic Fibrosis (CF) by improving CFTR mediated Cl- and HCO3- secretion by airway epithelial cells (AEC), leading to improved lung function and less frequent exacerbations and hospitalizations. However, studies have shown that CFTR modulators like ivacaftor, a component of ETI, has numerous effects on CF cells beyond improved CFTR channel function. Because little is known about the effect of ETI on CF AEC gene expression we exposed primary human AEC to ETI for 48 hours and interrogated the transcriptome by RNA-seq and qPCR. ETI increased CFTR Cl- secretion, and defensin gene expression (DEFB1) an observation consistent with reports of decreased bacterial burden in the lungs of people with CF (pwCF). ETI decreased MMP10 and MMP12 gene expression, suggesting that ETI may reduce proteolytic induced lung destruction in CF. ETI also reduced the expression of the stress response gene heme oxygenase (HMOX1). qPCR analysis confirmed DEFB1, HMOX1, MMP10 and MMP12 gene expression results observed by RNA-seq. Gene pathway analysis revealed that ETI decreased inflammatory signaling, cellular proliferation and MHC Class II antigen presentation. Collectively, these findings suggest that the clinical observation that ETI reduces lung infections in pwCF is related in part to drug induced increases in DEFB1, and that ETI may reduce lung damage by reducing MMP10 and MMP12 gene expression. Moreover, pathway analysis also identified several other genes responsible for the ETI induced reduction in inflammation observed in pwCF.

PMID:39437760 | DOI:10.1152/ajplung.00272.2024

Microbiol Spectr. 2024 Oct 22:e0227624. doi: 10.1128/spectrum.02276-24. Online ahead of print.

ABSTRACT

This multi-year study (2014-2019) compared identification of rare and unusual Gram-negative organisms (GNOs) by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (VITEK MS, bioMérieux, Laval Que.) to 16S rRNA gene sequencing (16S) according to our laboratories routine workflow; 16S is done if initial MALDI-TOF MS gave discordant, wrong, or no results. GNB isolates were first analyzed by standard phenotypic methods and MALDI-TOF MS using direct deposit-full formic acid extraction; proteomics was repeated if no result occurred. Medically approved 16S analyses were done using fast protocols. Isolate sequences were analyzed using the Integrated Database Network System (IDNS3) bacterial database (SmartGene, Lausanne, Switzerland). Three hundred thirty-one GNOs including 251 (76%) aerobic Gram-negative bacilli (GNB), 63 (19%) fastidious Gram-negative coccobacilli (fGNCBs), and 17 (5%) Campylobacterales (CAMPB) isolates were recovered from 304 specimens; >1 isolate was recovered from 19 (6%). GNOs were mainly recovered from blood cultures (31.6%) and lower respiratory specimens (43%) (one-half were isolated from cystic fibrosis patients). Accurate genus vs species identities were obtained for 67.7% and 32.5% aerobic GNBs, 73% and 60% fGNCBs, and 23.5% CAMPB (with no discrepant species), respectively. Wrong or no results were obtained for 81 (32.3%) aerobic GNBs, 17 (27%) fGNCBs, and 13 (72.2%) CAMPB. No results or misidentifications occurred for 33% of aerobic GNBs, 26% of fGNCBs, and 76.5% of CAMPB due to absence of species in the instrument's database. VITEK MS performance remained stable for aerobic GNBs and fGNCBs but improved for CAMPB with addition of Campylobacter rectus and Campylobacter curvus to the database. 16S remains important for identification of GNOs when proteomics fails.IMPORTANCEMatrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has transformed the identification of commonly encountered Gram-negative organisms (GNOs) in the clinical laboratory, but rare and unusual organisms continue to challenge the technology. This study verified performance of VITEK MS for identification of a broad range of rare and unusual clinical GNO isolates by our large reference laboratory workflow over a multi-year period. Although most GNOs were accurately identified by MALDI-TOF MS, a small number of clinical isolates (~1%-6%) required 16S sequencing for identification depending on the GNO category. Approximately one-third of aerobic Gram-negative bacilli (GNBs) and two-thirds of Campylobacterales could not be accurately identified by proteomics due to lack of an organism in the instrument's database. MALDI-TOF MS databases should be continuously updated and validated, and laboratories should have a workflow for identification of unusual or rarely encountered aerobic, fastidious, and Campylobacterales GNOs that includes 16S rRNA gene sequencing whenever proteomics cannot give a definitive identification.

PMID:39436124 | DOI:10.1128/spectrum.02276-24

mBio. 2024 Oct 22:e0244724. doi: 10.1128/mbio.02447-24. Online ahead of print.

ABSTRACT

The human pathogen Pseudomonas aeruginosa (Pa) poses a major risk for a range of severe infections, particularly lung infections in patients suffering from cystic fibrosis (CF). As previously reported, the virulent behavior of this pathogen is enhanced by elevated levels of Ca2+ that are commonly present in CF nasal and lung fluids. In addition, a Ca2+-binding EF-hand protein, EfhP (PA4107), was partially characterized and shown to be critical for the Ca2+-regulated virulence in P. aeruginosa. Here, we describe the rapid (10 min, 60 min), and adaptive (12 h) transcriptional responses of PAO1 to elevated Ca2+ detected by genome-wide RNA sequencing and show that efhP deletion significantly hindered both rapid and adaptive Ca2+ regulation. The most differentially regulated genes included multiple Fe sequestering mechanisms, a large number of extracytoplasmic function sigma factors (ECFσ), and several virulence factors, such as the production of pyocins. The Ca2+ regulation of Fe uptake was also observed in CF clinical isolates and appeared to involve the global regulator Fur. In addition, we showed that the efhP transcription is controlled by Ca2+ and Fe, and this regulation required a Ca2+-dependent two-component regulatory system CarSR. Furthermore, the efhP expression is significantly increased in CF clinical isolates and upon pathogen internalization into epithelial cells. Overall, the results established for the first time that Ca2+ controls Fe sequestering mechanisms in P. aeruginosa and that EfhP plays a key role in the regulatory interconnectedness between Ca2+ and Fe signaling pathways, the two distinct and important signaling pathways that guide the pathogen's adaptation to the host.IMPORTANCEPseudomonas aeruginosa (Pa) poses a major risk for severe infections, particularly in patients suffering from cystic fibrosis (CF). For the first time, kinetic RNA sequencing analysis identified Pa rapid and adaptive transcriptional responses to Ca2+ levels consistent with those present in CF respiratory fluids. The most highly upregulated processes include iron sequestering, iron starvation sigma factors, and self-lysis factors pyocins. An EF-hand Ca2+ sensor, EfhP, is required for at least 1/3 of the Ca2+ response, including the majority of the iron uptake mechanisms and the production of pyocins. Transcription of efhP itself is regulated by Ca2+ and Fe, and increases during interactions with host epithelial cells, suggesting the protein's important role in Pa infections. The findings establish the regulatory interconnectedness between Ca2+ and iron signaling pathways that shape Pa transcriptional responses. Therefore, understanding Pa's transcriptional response to Ca2+ and associated regulatory mechanisms will serve in the development of future therapeutics targeting Pa's dangerous infections.

PMID:39436074 | DOI:10.1128/mbio.02447-24

Pediatr Pulmonol. 2024 Oct 22. doi: 10.1002/ppul.27348. Online ahead of print.

NO ABSTRACT

PMID:39436050 | DOI:10.1002/ppul.27348

Int J Qual Stud Health Well-being. 2024 Dec;19(1):2419165. doi: 10.1080/17482631.2024.2419165. Epub 2024 Oct 22.

ABSTRACT

BACKGROUND: Cystic Fibrosis (CF) is a genetic life limiting disease that impacts upon quality of life. An aim of CF care is to preserve lung function, with physical activity (PA) being an important part of daily airway clearance. Ensuring children have opportunities to engage in PA at school should be an important part of their daily routine. It is important to gain parental perspectives on this, as they manage the daily care for their children. This study aims to explore parents' perceptions of school-based PA for their children with CF.

METHODS: Parents of children with CF (n = 10), from three regions of the UK (England, Wales and Northern Ireland) took part in online semi-structured interviews. Data were analysed using Interpretative Phenomenological Analysis (IPA).

RESULTS: Although parents recognized the benefits of school-based PA for their children, systemic barriers in the school setting often inhibit daily PA for children with CF, including teachers' misconceptions, emotional and physical barriers, and PA not being a priority.

CONCLUSION: Recommendations for practice have been developed to help engage children with CF in daily school-based PA in an inclusive way, with the hope of maintaining health outcomes for children with CF.

PMID:39434678 | DOI:10.1080/17482631.2024.2419165

J Magn Reson Imaging. 2024 Oct 22. doi: 10.1002/jmri.29627. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperpolarized 129Xe MRI assesses lung ventilation, often using the ventilation defect percentage (VDP). Unlike VDP, defect distribution index (DDI) quantifies spatial clustering of defects.

PURPOSE: To quantify spatial distribution of 129Xe ventilation defects using DDI across pulmonary diseases.

STUDY TYPE: Retrospective.

SUBJECTS: Four hundred twenty-one subjects (age = 23.1 ± 17.1, female = 230), comprising healthy controls (N = 60) and subjects with obstructive conditions (asthma [N = 25], bronchiolitis obliterans syndrome [BOS, N = 18], cystic fibrosis [CF, N = 90], lymphangioleiomyomatosis [LAM, N = 50]), restrictive conditions (bleomycin-treated cancer survivors [BLEO, N = 14]; fibrotic lung diseases [FLD, N = 92]), bone marrow transplantation (BMT, N = 53), and bronchopulmonary dysplasia (BPD, N = 19).

FIELD STRENGTH/SEQUENCE: 3 T, two-dimensional multi-slice gradient echo.

ASSESSMENT: Whole-lung mean DDI was extracted from DDI maps; correlated with VDP (percent of pixels <60% of whole-lung mean signal intensity) and pulmonary function tests (PFTs) including FEV1, FVC, and FEV1/FVC. DDI and DDI/VDP, a marker of defect clustering, were compared across diseases.

STATISTICAL TESTS: Pearson correlation analysis and Kruskal-Wallis tests. P < 0.0056 for disease groups, P < 0.0125 for categories.

RESULTS: DDI was significantly elevated in BMT (8.3 ± 11.5), BOS (30.1 ± 57.5), BPD (16.0 ± 46.8), CF (15.4 ± 27.2), and LAM (12.6 ± 34.2) compared to controls (1.8 ± 3.1). DDI correlated significantly with VDP in all groups (r ≥ 0.56) except BLEO, and with PFTs in CF, FLD, and LAM (r ≥ 0.56). Obstructive groups had significantly higher mean DDI (14.0 ± 32.0) than controls (1.8 ± 3.0) and restrictive groups (4.0 ± 12.0). DDI/VDP was significantly lower in the restrictive group (0.6 ± 0.6) than controls (0.8 ± 0.6) and obstructive group (1.0 ± 1.0).

DATA CONCLUSION: DDI may provide insights into the distribution of ventilation defects across diseases.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

PMID:39434582 | DOI:10.1002/jmri.29627

BMJ Support Palliat Care. 2024 Oct 21:spcare-2024-005015. doi: 10.1136/spcare-2024-005015. Online ahead of print.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) in children requires complex and time-consuming daily care, presenting significant challenges for families and caregivers. Family caregivers caring for children with CF report diverse and complex needs.

OBJECTIVE: This review aimed to identify the supportive care needs of family caregivers of children with CF.

REVIEW METHODS: This scoping review was conducted to identify the supportive care needs of family caregivers for children with CF using the methodology proposed by Arksey and O'Malley. The Preferred Reporting Items for Systematic review and Meta-Analysis extension for Scoping Reviews checklist was used as a guide. The inclusion criteria included full-text quantitative and qualitative English articles from January 2000 to Apr 2024.

DATA SOURCES: Structured searches were conducted using Magiran, MEDLINE (PubMed), Scopus, ScienceDirect, SID (Science Information Database), Web of Science and Google Scholar search engines.

FINDINGS: A search across six databases, including Magiran (96), PubMed (680), Scopus (828), ScienceDirect (972), SID (Science Information Database) (47) and Web of Science (409), identified 3032 records. An additional 1185 related articles were found through a manual search of the reference lists and the Google Scholar search engine bringing the total to 4217. Out of 4217 initial articles, 21 eligible articles were reviewed. The findings from this study indicated that family caregivers of children with CF face multidimensional needs requiring comprehensive attention and support including educational/informational, psychological/emotional, spiritual, social, family-related, health and child development and growth needs.

CONCLUSION: Addressing the needs of family caregivers of children with CF requires a multidimensional approach including multidisciplinary team support across various domains.

PMID:39433359 | DOI:10.1136/spcare-2024-005015

Lancet Respir Med. 2024 Oct 18:S2213-2600(24)00295-9. doi: 10.1016/S2213-2600(24)00295-9. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension (PAH) is a vascular disease characterised by restricted flow and high pressure through the pulmonary arteries, leading to progressive right heart failure and death. This study reports the global burden of PAH, leveraging all available data and using methodology of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to understand the epidemiology of this under-researched and morbid disease.

METHODS: Prior to the current effort, the burden of PAH was included in GBD as a non-specific contributor to "other cardiovascular and circulatory disease" burden. In this study, PAH was distinguished as its own cause of death and disability in GBD, producing comparable and consistent estimates of PAH burden. We used epidemiological and vital registry data to estimate the non-fatal and fatal burden of PAH in 204 countries and territories from 1990 to 2021 using standard GBD modelling approaches. We specifically focused on PAH (group 1 pulmonary hypertension), and did not include pulmonary hypertension groups 2-5.

FINDINGS: In 2021, there were an estimated 192 000 (95% uncertainty interval [UI] 155 000-236 000) prevalent cases of PAH globally. Of these, 119 000 (95 900-146 000) were in females (62%) and 73 100 (58 900-89 600) in males (38%). The age-standardised prevalence was 2·28 cases per 100 000 population (95% UI 1·85-2·80). Prevalence increased with age such that the highest prevalence was among individuals aged 75-79 years. In 2021, there were 22 000 deaths (18 200-25 400) attributed to PAH globally, with an age-standardised mortality rate of 0·27 deaths from PAH per 100 000 population (0·23-0·32). The burden of disease appears to be improving over time (38·2% improvement in age-standardised years of life lost [YLLs] in 2021 relative to 1990). YLLs attributed to PAH were similar to estimates for conditions such as chronic myeloid leukaemia, multiple sclerosis, and Crohn's disease.

INTERPRETATION: PAH is a rare but fatal disease that accounts for a considerable health-associated burden worldwide. PAH is disproportionally diagnosed among females and older adults.

FUNDING: Cardiovascular Medical Research and Education Fund and the Bill & Melinda Gates Foundation.

PMID:39433052 | DOI:10.1016/S2213-2600(24)00295-9

Clin Case Rep. 2024 Oct 17;12(10):e9481. doi: 10.1002/ccr3.9481. eCollection 2024 Oct.

ABSTRACT

Gallstones, microlithiasis, gallbladder sludge, and micro-gallbladder are frequently reported in cystic fibrosis patients, and modulators could modify gallbladder disease, probably reducing biliary secretions viscosity.

PMID:39430919 | PMC:PMC11486912 | DOI:10.1002/ccr3.9481

Commun Integr Biol. 2024 Oct 17;17(1):2415598. doi: 10.1080/19420889.2024.2415598. eCollection 2024.

ABSTRACT

Quorum sensing (QS) is a critical bacterial communication system regulating behaviors like biofilm formation, virulence, and antibiotic resistance. This review highlights QS's role in polymicrobial infections, where bacterial species interactions enhance antibiotic resistance. We examine QS mechanisms, such as acyl-homoserine lactones (AHLs) in Gram-negative bacteria and autoinducing peptides (AIPs) in Gram-positive bacteria, and their impact on biofilm-associated antibiotic resistance. The challenges uniquely associated with polymicrobial infections, such as those found in cystic fibrosis lung infections, chronic wound infections, and medical device infections, are also summarized. Furthermore, we explore various laboratory models, including flow cells and dual-species culture models, used to study QS interactions in polymicrobial environments. The review also discusses promising quorum sensing inhibitors (QSIs), such as furanones and AHL analogs, which have demonstrated efficacy in reducing biofilm formation and virulence in laboratory and clinical studies. By addressing the interplay between QS and antibiotic resistance, this paper aims to advance therapeutic strategies that disrupt bacterial communication and improve antibiotic efficacy, ultimately mitigating the global challenge of antibiotic resistance in polymicrobial infections.

PMID:39430726 | PMC:PMC11487952 | DOI:10.1080/19420889.2024.2415598

JAC Antimicrob Resist. 2024 Oct 17;6(5):dlae160. doi: 10.1093/jacamr/dlae160. eCollection 2024 Oct.

ABSTRACT

BACKGROUND: Chronic bronchopulmonary infection due to MRSA in people with cystic fibrosis (pwCF) has been associated with accelerated decline in lung function, increased hospitalizations and increased mortality.

MATERIAL AND METHODS: We studied microbiological and genomic characteristics of MRSA isolates recovered from pwCF in two Spanish multicentre studies (2013, 2021). Antimicrobial susceptibility was performed. WGS was carried out to determine population structure [MLST, spa-typing, staphylococcal cassette chromosome mec (SCCmec)], resistome and virulome. Clinical charts of MRSA-infected and MRSA-non-infected pwCF were also reviewed.

RESULTS: MRSA infection prevalence decreased between 2013 (29/341, 8.5%) and 2021 (21/326, 6.4%) (P = 0.378). Differences in lung function were observed between infected and non-infected patients (P < 0.005). A higher prevalence of hospital-acquired (HA) clones was found compared with community-acquired (CA) clones (2013: 67% versus 33%; and 2021: 71% versus 29%). Overall, we noted clustering of isolates based on year of sampling, type of acquisition and clonal complex (CC). HA-MRSA population was dominated by CC5, with ST125-MRSA-IVc-t067 the most prevalent lineage (37%). A higher clonal diversity was detected among CA-MRSA. One Panton-Valentine leucocidin (PVL)-positive strain (ST8-MRSA-IV) and three strains of porcine origin (two ST398-MRSA-V-t011, one ST398-MRSA-V-t8567) were found. Additionally, acquired resistance genes (n = 24) were detected, including the cfr gene conferring linezolid resistance. A higher gentamicin resistance was found in 2021 (42%) compared with 2013 (7%) (P = 0.046), associated with the aac(6')-aph(2″) gene.

CONCLUSIONS: Despite a decrease in MRSA prevalence, we showed its potential impact on CF severity and progression. Moreover, we observed great genotypic and phenotypic diversity in MRSA isolates from pwCF as well as an MDR trait.

PMID:39429234 | PMC:PMC11487781 | DOI:10.1093/jacamr/dlae160

Dis Model Mech. 2024 Oct 21:dmm.052074. doi: 10.1242/dmm.052074. Online ahead of print.

ABSTRACT

Airway mucous cell metaplasia is a significant feature of many chronic airway diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma. However, the mechanisms underlying this process remain poorly understood. Here, we employ in vivo mouse genetic models to demonstrate that Hippo and p53 cooperate to modulate the differentiation of club cells into goblet cells. We reveal that ablation of Mst1 and Mst1 (Mst1/2), the core components of Hippo signaling, significantly reduces mucous metaplasia in the lung airways in a lipopolysaccharide (LPS)-induced lung inflammation murine model while promoting club cell proliferation in a Yap-dependent manner. Additionally, we show that deleting Mst1/2 is sufficient to suppress p53 deficiency-mediated goblet cell metaplasia. Finally, single-cell RNA analysis reveals a downregulation of Yap and p53 signaling in goblet cells in the human airways. These findings underscore the important role of Hippo and p53 signaling in regulating airway mucous metaplasia.

PMID:39428818 | DOI:10.1242/dmm.052074