CMAJ. 2025 Jan 19;197(2):E45-E46. doi: 10.1503/cmaj.241452.

NO ABSTRACT

PMID:39832926 | DOI:10.1503/cmaj.241452

J Particip Med. 2025 Jan 20;17:e49941. doi: 10.2196/49941.

ABSTRACT

BACKGROUND: Adolescents and young adults (AYA) with cystic fibrosis (CF) are at risk for deviating from their daily treatment regimen due to significant time burden, complicated daily therapies, and life stressors. Developing patient-centric, effective, engaging, and practical behavioral interventions is vital to help sustain therapeutically meaningful self-management.

OBJECTIVE: This study aimed to devise and refine a patient-centered telecoaching intervention to foster self-management in AYA with CF using a combination of intervention development approaches, including an evidence- and theory-based approach (ie, applying existing theories and research evidence for behavior change) and a target population-centered approach (ie, intervention refinement based on the perspectives and actions of those individuals who will use it).

METHODS: AYA with CF, their caregivers, and health professionals from their CF care teams were recruited to take part in focus groups (or individual qualitative interviews) through a video call interface to (1) obtain perspectives on the overall structure and logistics of the intervention (ie, Step 1) and (2) refine the overall framework of the intervention and obtain feedback on feasibility, content, materials, and coach training (ie, Step 2). Qualitative data were analyzed using a reflexive thematic analysis process. Results were used to create and then modify the intervention structure and content in response to community partner input.

RESULTS: For Step 1, a total of 31 AYA and 20 clinicians took part in focus groups or interviews, resulting in 2 broad themes: (1) video call experience and (2) logistics and content of intervention. For Step 2, a total of 22 AYA, 18 clinicians, and 11 caregivers completed focus groups or interviews, yielding 3 major themes: (1) intervention structure, (2) intervention materials, and (3) session-specific feedback. Our Step 1 qualitative findings helped inform the structure (eg, telecoaching session frequency and duration) and approach of the telecoaching intervention. Step 2 qualitative results generally suggested that community partners perceived the feasibility and practicality of the proposed telecoaching intervention in promoting self-management in the face of complex treatment regimens. Extensive specific feedback was used to refine our telecoaching intervention before its efficacy testing in subsequent research. The diverse community partner input was critical in optimizing and tailoring our telecoaching intervention.

CONCLUSIONS: This study documents the methods and results for engaging key community partners in creating an evidence-based behavioral intervention to promote self-management in AYA with CF. Incorporating the lived experiences and perspectives of community partners is essential when devising tailored and patient-centered interventions.

PMID:39832355 | DOI:10.2196/49941

Cochrane Database Syst Rev. 2025 Jan 20;1:CD009730. doi: 10.1002/14651858.CD009730.pub3.

ABSTRACT

BACKGROUND: Cystic fibrosis is a multisystem disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous (IV) antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned. This is an update of a previously published review.

OBJECTIVES: To establish whether IV antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short-term and long-term clinical outcomes.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers. Date of last search of Cochrane Trials Register: 19 June 2024.

SELECTION CRITERIA: Randomised controlled trials and the first treatment cycle of cross-over studies comparing IV antibiotics (given alone or in an antibiotic combination) with placebo, or inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation. Studies comparing different IV antibiotic regimens were also eligible.

DATA COLLECTION AND ANALYSIS: We assessed studies for eligibility and risk of bias, and extracted data. Using GRADE, we assessed the certainty of the evidence for the outcomes lung function % predicted (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)), time to next exacerbation and quality of life.

MAIN RESULTS: We included 45 studies involving 2810 participants. The included studies were mostly small, and inadequately reported, many of which were quite old. The certainty of the evidence was mostly low. Combined intravenous antibiotics versus placebo Data reported for absolute change in % predicted FEV1 and FVC suggested a possible improvement in favour of IV antibiotics, but the evidence is very uncertain (1 study, 12 participants; very low-certainty evidence). The study did not measure time to next exacerbation or quality of life. Intravenous versus nebulised antibiotics Five studies (122 participants) reported FEV1, with analysable data only from one study (16 participants). We found no difference between groups (moderate-certainty evidence). Three studies (91 participants) reported on FVC, with analysable data from only one study (54 participants). We are very uncertain on the effect of nebulised antibiotics (very low-certainty evidence). In one study, the 16 participants on nebulised plus IV antibiotics had a lower mean number of days to next exacerbation than those on combined IV antibiotics (low-certainty evidence), but we found no difference in quality of life between groups (low-certainty evidence). Intravenous versus oral antibiotics Three studies (172 participants) reported no difference in different measures of lung function. We found no difference in analysable data between IV and oral antibiotic regimens in either FEV1 % predicted or FVC % predicted (1 study, 24 participants; low-certainty evidence) or in the time to the next exacerbation (1 study, 108 participants; very low-certainty evidence). No study measured quality of life. Intravenous antibiotic regimens compared One study (analysed as two data sets) compared the duration of IV antibiotic regimens between two groups (split according to initial antibiotic response). The first part was a non-inferiority study in 214 early treatment responders to establish whether 10 days of IV antibiotic treatment was as effective as 14 days. Second, investigators looked at whether 14 or 21 days of IV antibiotics were more effective in 705 participants who did not respond early to treatment. We found no difference in FEV1 % predicted with any duration of treatment (919 participants; high-certainty evidence) or the time to next exacerbation (information later taken from registry data). Investigators did not report FVC or quality of life. Other comparisons We also found little or no difference in lung function when comparing single IV antibiotic regimens to placebo (2 studies, 70 participants), or in lung function and time to next exacerbation when comparing different single antibiotic regimens (2 studies, 95 participants). There may be a greater improvement in lung function in participants receiving combined IV antibiotics compared to single IV antibiotics (6 studies, 265 participants; low- to very low-certainty evidence), but probably no difference in the time to next exacerbation (1 study, 34 participants; low-certainty evidence). Four studies compared a single IV antibiotic plus placebo to a combined IV antibiotic regimen with high levels of heterogeneity in the results. We are very uncertain if there is any difference between groups in lung function (4 studies, 214 participants) and there may be little or no difference to being re-admitted to hospital for an exacerbation (2 studies, 104 participants). Nine studies (417 participants) compared combined IV antibiotic regimens with a great variation in drugs. We identified no differences in any measure of lung function or the time to next exacerbation between different regimens (low- to very low-certainty evidence). There were mixed results for adverse events across all comparisons; common adverse effects included elevated liver function tests, gastrointestinal events and haematological abnormalities. There were limited data for other secondary outcomes, such as weight, and there was no evidence of treatment effect.

AUTHORS' CONCLUSIONS: The evidence of benefit from administering IV antibiotics for pulmonary exacerbations in cystic fibrosis is often poor, especially in terms of size of studies and risk of bias, particularly in older studies. We are not certain whether there is any difference between specific antibiotic combinations, and neither is there evidence of a difference between the IV route and the inhaled or oral routes. There is limited evidence that shorter antibiotic duration in adults who respond early to treatment is not different to a longer period of treatment. There remain several unanswered questions regarding optimal IV antibiotic treatment regimens.

PMID:39831540 | DOI:10.1002/14651858.CD009730.pub3

World Allergy Organ J. 2024 Dec 27;18(1):101016. doi: 10.1016/j.waojou.2024.101016. eCollection 2025 Jan.

ABSTRACT

BACKGROUND: This study aimed to evaluate the impact of severe asthma (SA) treatments after 12 months in achieving clinical remission (CR) within the context of the Severe Asthma Network in Italy (SANI) using the recent SANI definition of CR on treatment.

METHODS: CR has been defined by SANI as complete, partial, and no CR. Complete CR is defined by the absence of oral corticosteroids (OCS), no symptoms, no exacerbations, and stable lung function, and partial CR requires the absence of OCS and the fulfillment of 2 out of the other 3 criteria. Patients who do not meet the previous criteria do not reach CR.

RESULTS: After 12 months of treatment, 283 patients were selected to evaluate the effectiveness of biologics (225 patients) and inhaled therapy (58 patients) in achieving CR. Among patients treated with biologic agents, 45.8% reached complete CR, 23.1% partial CR, and 31.1% no CR. Differences in CR achievement according to type of biologic agent administered were observed. Interesting results were found when assessing the inhaled therapy (ICS/LABA/LAMA and no biologics) effectiveness: 34.5% patients reached complete CR, 34.5% partial CR, and 31.0% did not reach CR. This finding is noteworthy since it further supports the efficacy of inhaled treatment in certain SA patients and highlights the relevance of using CR as a modern outcome of SA treatments. Chronic rhinosinusitis with nasal polyps (CRSwNP) comorbidity was associated, though not significantly, with CR achievement in patients treated with biologics. Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores significantly impacted CR (p = 0.003 and p = 0.027, respectively), while biomarkers, namely IgE, blood eosinophils, or fractional exhaled nitric oxide (FeNO), were not associated with CR achievement.

CONCLUSIONS: This study confirmed the effectiveness of biologics in reaching CR and demonstrated also inhaled therapies able to achieve CR. These innovative findings should encourage post hoc analysis of randomized clinical trials or even retrospective analysis of SA patient cohorts to evaluate CR with different inhaled treatments and further define the populations eligible for each treatment.

TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06625216; Central Ethics Committee: Comitato Etico Area Vasta Nord-Ovest Toscana (study number 1245/2016, protocol number:73714).

PMID:39829953 | PMC:PMC11741032 | DOI:10.1016/j.waojou.2024.101016

Sci Rep. 2025 Jan 18;15(1):2390. doi: 10.1038/s41598-025-86211-8.

ABSTRACT

Burkholderia cenocepacia H111 is an obligate aerobic bacterium which has been isolated from a cystic fibrosis (CF) patient. In CF lungs the environment is considered micro-oxic or even oxygen-depleted due to bacterial activities and limited oxygen diffusion in the mucus layer. To adapt to low oxygen concentrations, bacteria possess multiple terminal oxidases. In this study, we identified six terminal oxidases of B. cenocepacia H111 and constructed reporter strains to monitor their expression in different environments. While the heme-copper oxidase aa3 (cta) was constitutively expressed, the bd-1 oxidase (cyd) was induced under oxygen-limited growth conditions. The cyanide-insensitive bd-type terminal oxidase (cio-1) was mainly expressed in cells grown on the surface of solid medium or in liquid cultures in presence of cyanide, which is known to be produced in the CF lung by the often co-residing CF pathogen Pseudomonas aeruginosa. Indeed, a cio-1 insertional mutant was not able to grow in the presence of cyanide confirming the important role of Cio-1 in cyanide resistance. The caa3 oxidase (caa), was only expressed under nutrient limitation when cells were grown on the surface of solid medium. We also investigated the involvement of two regulatory systems, Anr and RoxS/RoxR, in the expression of cio-1 and cyd. Our data suggest, that, given that Cio-1 is only present in prokaryotes and plays an important role in the defense against cyanide-producing P. aeruginosa, it may be a valuable drug target for treatment of polymicrobial infections in CF patients.

PMID:39827173 | DOI:10.1038/s41598-025-86211-8

Respir Res. 2025 Jan 18;26(1):19. doi: 10.1186/s12931-024-03089-2.

ABSTRACT

This retrospective population-based study investigated the impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on inhaled medication adherence in people with cystic fibrosis (pwCF). Prescription refill rate (PRR) for several inhaled medications were compared before and after ETI introduction in three major Italian CF centers. We found a significant decrease in PRR for most inhaled antibiotics and dornase-alpha after ETI implementation.This suggests that patients may be reducing their adherence to inhaled medications, potentially due to improved respiratory symptoms and quality of life. The study highlights the challenges of maintaining adherence to chronic inhaled medications in pwCF, even after the introduction of breakthrough therapies like ETI. Monitoring adherence remains crucial for optimizing patient outcomes, and the PRR emerges as a valuable tool for tracking adherence in real-world settings.

PMID:39827103 | DOI:10.1186/s12931-024-03089-2

J Thorac Cardiovasc Surg. 2025 Feb;169(2):484-504. doi: 10.1016/j.jtcvs.2024.08.052.

ABSTRACT

BACKGROUND: Donor lung procurement and preservation is critical for lung transplantation success. Unfortunately, the large variability in techniques impacts organ utilization rates and transplantation outcomes. Compounding this variation, recent developments in cold static preservation and new technological advances with machine perfusion have increased the complexity of the procedure. The objective of the American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) expert panel was to make evidence-based recommendations for best practices in donor lung procurement and preservation based on review of the existing literature.

METHODS: The AATS CPSC assembled an expert panel of 16 lung transplantation surgeons from 14 centers who developed a consensus document of recommendations. The panel was divided into 7 subgroups covering (1) intraoperative donor assessment, (2) surgical techniques, (3) ex situ static lung preservation methods, (4) hypothermic preservation, (5) normothermic ex vivo lung perfusion (EVLP), (6) donation after circulatory death (DCD) and normothermic regional perfusion, and (7) donor management centers, organ assessment centers, and third-party procurement teams. Following a focused literature review, each subgroup formulated recommendation statements for each subtopic, which were reviewed and further refined using a Delphi process until a 75% consensus was achieved on each final statement by the voting group.

RESULTS: The expert panel achieved consensus on 34 recommendations for current best practices in donor lung procurement and preservation both in brain-dead as well as DCD donation. The use of new methods of cold preservation, the role of EVLP, and DCD with and without concomitant heart donation are described in detail.

CONCLUSIONS: Consistent and best practices in donor lung procurement and preservation are critical to improve both lung transplantation numbers as well as recipient outcomes. The recommendations described here provide guidance for professionals involved in the care of patients with end-stage lung disease considered for transplantation.

PMID:39826938 | DOI:10.1016/j.jtcvs.2024.08.052

ACS Nano. 2025 Jan 18. doi: 10.1021/acsnano.4c14927. Online ahead of print.

ABSTRACT

The abnormally viscous and thick mucus is a hallmark of cystic fibrosis (CF). How the mutated CF gene causes abnormal mucus remains an unanswered question of paramount interest. Mucus is produced by the hydration of gel-forming mucin macromolecules that are stored in intracellular granules prior to release. Current understanding of mucin/mucus structure before and after secretion remains limited, and contradictory models exist. Here, we used a molecular viscometer and fluorescence lifetime imaging of human bronchoepithelial cells (Normal and CF) to measure nanometer-scale viscosity. We found significantly elevated intraluminal nanoviscosity in a population of CF mucin granules, indicating an intrinsic, presecretory mucin defect. Nanoviscosity influences protein conformational dynamics and function. Its elevation along the protein secretory pathway could arise from molecular overcrowding, impacting mucin's post-translational processing, hydration, and mucus rheology after release. The nanoviscosity of secreted CF mucus was elevated compared to that of non-CF. Interestingly, it was higher after release than in granules. Validation experiments indicate that reduced mobility of water hydrating mucin macromolecules may contribute to the high nanoviscosity in mucus and mucin granules. This suggests that mucins have a weakly ordered state in granules but adopt a highly ordered, nematic crystalline structure when secreted. This challenges the traditional view of mucus as a porous agarose-like gel and suggests an alternative model for mucin organization before and after secretion. Our study also indicates that endoplasmic reticulum stress due to molecular overcrowding could contribute to mucus pathogenesis in CF cells. It encourages the development of therapeutics that target presecretory mechanisms in CF and other muco-obstructive lung diseases.

PMID:39825840 | DOI:10.1021/acsnano.4c14927

Hum Mol Genet. 2025 Jan 17:ddaf007. doi: 10.1093/hmg/ddaf007. Online ahead of print.

ABSTRACT

BACKGROUND: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

METHODS: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk. For replication, we used whole exome sequencing data from UK Biobank (UKB; 5126 cases and 20 504 controls matched 4:1 based on genetic distance, age, and sex), and extended our analyses to all other heterozygous CFTR variants annotated as CF-causing.

RESULTS: In our meta-analysis of GECCO-CORECT-CCFR-ARIC, the odds ratio (OR) for CRC risk associated with Phe508del was 1.11 (P = 0.010). In our UKB replication, the OR for CRC risk associated with Phe508del was 1.28 (P = 0.002). The sequencing data from UKB also revealed an association between the presence of any other single CF-causing variant (excluding Phe508del) and CRC risk (OR = 1.33; P = 0.030). When stratifying CFTR variants by functional class, class I variants (no protein produced) had a stronger association (OR = 1.77; p = 0.002), while class II variants (misfolding and retention of the protein in the endoplasmic reticulum) other than Phe508del (OR = 1.75; p = 0.107) had similar effect size as Phe508del, and variants in classes III-VI had non-significant ORs less than 1.0 and/or were not present in cases.

CONCLUSIONS: CF-causing heterozygous variants, especially class I variants, are associated with a modest but statistically significant increased CRC risk. More research is needed to explain the biology underlying these associations.

PMID:39825500 | DOI:10.1093/hmg/ddaf007

Adv Exp Med Biol. 2025 Jan 18. doi: 10.1007/5584_2024_829. Online ahead of print.

ABSTRACT

Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies. In this communication, we briefly present existing in vivo models for cystic fibrosis and their limitations in replicating human respiratory infections. We then present a novel, 3D-printed, cytocompatible microfluidic lung-on-a-chip device, designed to simulate the human lung environment, and with possible use in recapitulating general infectious diseases.Our device enables the colonisation of fully differentiated lung epithelia at an air-liquid interface with Pseudomonas aeruginosa, a key pathogen in many severe infections. By incorporating dynamic flow, we replicate the clearance of bacterial toxins and planktonic cells, simulating both acute and chronic infections. This platform supports real-time monitoring of therapeutic interventions, mimics repeated drug administrations as in clinical settings, and facilitates the analysis of colony-forming units and cytokine secretion over time. Our findings indicate that this lung-on-a-chip device has significant potential for advancing infectious disease research, in optimizing treatment strategies against infections and in developing novel treatments.

PMID:39825043 | DOI:10.1007/5584_2024_829

Sci Rep. 2025 Jan 17;15(1):2247. doi: 10.1038/s41598-025-86010-1.

ABSTRACT

Clinical trials demonstrate the short-term efficacy of dual CFTR modulators, but long-term real-world data is limited. We aimed to investigate the effects of 24-month lumacaftor/ivacaftor (LUM/IVA) therapy in pediatric CF patients (pwCF). This observational study included pwCF homozygous for F508del mutation treated between 2021 and 2023. We report data for the first 24 months from therapy initiation. Variables were analyzed separately for ages 2-5, 6-11, and over 12. Data from 49 pwCF (median age: 9.3 years (5.5-14.2)) showed that ppFEV1 values after a transient increase at 12 months, decreased from 102% (82-114) at baseline to 87% (74-96) at 24 months. The decrease was more pronounced with higher initial ppFEV1. Median sweat chloride concentration decreased from 75 mmol/L (69-82) to 57 mmol/L (43-70) without any association with respiratory function change. Median BMI z-score increased from - 0.81 (- 1.37-0.49) to - 0.39 (- 0.88 to - 0.04) (p = 0.288), and the proportion of underweight and overweight children decreased. Skeletal muscle mass remained stable, while fat mass significantly increased (p = 0.011). Fecal elastase levels improved, especially among younger patients. These findings underscore the potential benefits of early initiation of CFTR modulator therapy in pediatric CF patients, highlighting improvements in nutritional status and pancreatic function.

PMID:39824960 | DOI:10.1038/s41598-025-86010-1

Sci Rep. 2025 Jan 17;15(1):2222. doi: 10.1038/s41598-024-82500-w.

ABSTRACT

Pseudomonas aeruginosa is a Gram-negative bacterium that is notorious for airway infections in cystic fibrosis (CF) subjects. Bacterial quorum sensing (QS) coordinates virulence factor expression and biofilm formation at population level. Better understanding of QS in the bacterium-host interaction is required. Here, we set up a new P. aeruginosa infection model, using 2D upper airway nasal organoids that were derived from 3D organoids. Using dual RNA-sequencing, we dissected the interaction between organoid epithelial cells and WT or QS-mutant P. aeruginosa strains. Since only a single healthy individual and a single CF subject were used as donors for the organoids, conclusions about CF-specific effects could not be deduced. However, P. aeruginosa induced epithelial inflammation, whereas QS signaling did not affect the epithelial airway cells. Conversely, the epithelium influenced infection-related processes of P. aeruginosa, including QS-mediated regulation. Comparison of our model with samples from the airways of CF subjects indicated that our model recapitulates important aspects of infection in vivo. Hence, the 2D airway organoid infection model is relevant and may help to reduce the future burden of P. aeruginosa infections in CF.

PMID:39824906 | DOI:10.1038/s41598-024-82500-w

J Cyst Fibros. 2025 Jan 16:S1569-1993(25)00008-6. doi: 10.1016/j.jcf.2025.01.006. Online ahead of print.

ABSTRACT

BACKGROUND: Highly effective modulator therapies (HEMT) including ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ETI) have transformed treatment for people with cystic fibrosis (pwCF). However, non-HEMT-responsive mutations are more common in pwCF of non-White race/ethnicity; introduction of HEMT might have exacerbated racial/ethnic disparities in CF care.

METHODS: Using the Scientific Registry of Transplant Recipients, we identified all lung transplant candidates and recipients 05/2005-12/2022 and categorized them by diagnosis (CF/non-CF), race/ethnicity (non-Hispanic White/Black/Hispanic) and era [Pre-HEMT (2005-1/30/2012), IVA (1/31/2012-10/30/2019), ETI (10/31/2019-12/31/2022)]. We compared the percentage of patients listed, delisted/died, or transplanted by race/ethnicity and era.

RESULTS: 34,659 lung transplants were performed: 10,521 pre-HEMT, 15,944 in IVA era, and 7,888 in ETI era. Over the three eras, the percentage of lung recipients with CF of White race decreased (94.5 % to 92.4 % to 78.4 %) and of Black race (1.7 % to 2.4 % to 5.7 %) or Hispanic ethnicity increased (3.5 % to 4.6 % to 14.2 %; p < 0.001). Similarly, among candidates listed for CF over the three eras, the percentage that were of White race decreased (82.0 % vs. 78.6 % vs. 71.0 %) and of Black race (9.2 % vs. 10.0 % vs. 10.3 %) or Hispanic ethnicity increased (6.4 % vs. 8.6 % vs. 13.6 %; p < 0.001).

CONCLUSION: The introduction of HEMT appears to have benefitted CF lung transplant candidates and recipients of Black race or Hispanic ethnicity less than those of White race. This is likely due to the higher prevalence of HEMT-ineligible CFTR mutations among Black and Hispanic patients and underscores the need for therapies aimed at non-HEMT-responsive mutations prevalent in these racial/ethnic populations.

PMID:39824680 | DOI:10.1016/j.jcf.2025.01.006

J Glob Antimicrob Resist. 2025 Jan 15:S2213-7165(25)00007-4. doi: 10.1016/j.jgar.2025.01.002. Online ahead of print.

ABSTRACT

OBJECTIVES: Pandoraea apista is notable for its multidrug resistance and is frequently identified in patients with cystic fibrosis or other chronic lung diseases, where it contributes to persistent lung infections. In this study, we describe a strain of P. apista harboring the blaOXA-153, isolated from the bronchoalveolar lavage (BAL) fluid of an inpatient in China.

METHODS: The genomic DNA of P. apista strain PA167 was sequenced using the Illumina NovaSeq 6000 system and assembled with SPAdes v.3.13.0. Antimicrobial resistance genes (ARGs) were identified using ResFinder v.3.2 within the ABRicate v.0.9.0. Phylogenetic analysis was performed using the Snippy v.4.6.0.

RESULTS: The genome sequence of P. apista strain PA167 comprises 5,580,873 bp, with 4,926 protein-coding sequences, 4 ncRNAs, 59 tRNAs, and 3 rRNA operons. Only one ARG was identified: blaOXA-153. PA167 exhibited resistance to multiple antibiotics, including cephalosporins and carbapenems, and was susceptible only to sulfamethoxazole/trimethoprim. Twenty-four P. apista strains, including PA167, could be retrieved from the NCBI database, all carrying the blaOXA-153. Complete genomic sequencing of five strains confirmed the chromosomal presence of blaOXA-153. The isolation sources of these 24 strains were predominantly clinical samples, mainly respiratory specimens, with some strains isolated from environmental sources.

CONCLUSION: Here, we present the genome sequence of a P. apista strain carrying the blaOXA-153, marking the first isolation of this strain from a clinical setting in China. The potential for future epidemic spread highlights the necessity for targeted antimicrobial strategies.

PMID:39824284 | DOI:10.1016/j.jgar.2025.01.002

PLoS One. 2025 Jan 17;20(1):e0313051. doi: 10.1371/journal.pone.0313051. eCollection 2025.

ABSTRACT

OBJECTIVE: Managing blood glucose levels is challenging for elite athletes with type 1 diabetes (T1D) as competition can cause unpredictable fluctuations. While fear of hypoglycemia during physical activity is well documented, research on hyperglycemia-related anxiety (HRA) is limited. HRA refers to the heightened fear that hyperglycemia-related symptoms will impair functioning. This study investigates current strategies employed to mitigate HRA during competition and the development of alternative approaches.

RESEARCH DESIGN AND METHODS: Elite athletes with TID, aged >14 who self-reported HRA during competition were recruited. Elite athletes were defined as individuals exercising >10 hours per week whose athletic performance has achieved the highest competition level. 60 to 90-minute virtual semi-structured interviews were analyzed using an Interpretative Phenomenological Analysis.

RESULTS: Ten elite athletes with T1D (average age 25 ± 3 years; T1D duration 12 ± 8 years; number of competitions per year 27 ± 19; training time per week 12 ± 6 hours) reported the strategies they currently use to mitigate HRA. These strategies include managing insulin and nutrition intake, embracing social support networks, using technology, practicing relaxation techniques, establishing routines, performing pre-competition aerobic exercise, and maintaining adequate sleep hygiene. Several additional approaches that could be implemented were identified including establishing targeted support networks, developing peer-reviewed resources on HRA, ensuring support teams have sufficient tools, and improving existing technology.

CONCLUSIONS: Elite athletes with T1D use physiological and psychological strategies to mitigate HRA during competition. This finding highlights the need for increased support and education for these athletes, and advancements in technology. A multidisciplinary approach involving healthcare professionals, athletic staff, and peer mentors could help integrate personalized anxiety management and diabetes care strategies into training regimens, enhancing both mental resilience and performance outcomes for athletes with T1D.

PMID:39823464 | DOI:10.1371/journal.pone.0313051

Cardiovasc Intervent Radiol. 2025 Jan 16. doi: 10.1007/s00270-024-03918-3. Online ahead of print.

ABSTRACT

Pediatric pain management presents unique challenges due to the intrinsic characteristics of children such as their developmental stages, communication barriers, and varying pain perceptions. Life-limiting conditions affecting children are a growing medical concern, requiring a comprehensive, multidisciplinary approach to improve quality of life or ensure a dignified end of life. Interventional radiology (IR) plays a critical role in this strategy, similar to its role in adult care. Not only life-limiting conditions pose a challenge in pediatric chronic pain management, but also other benign chronic diseases (e.g., cystic fibrosis, muscular dystrophy, neurodegenerative disorders, metabolic disorders). This review focuses on specific IR strategies for pediatric pain management, including ablation, embolization/chemoembolization, and nerve blocks. It emphasizes the importance of tailored approaches for pediatric patients, considering genetic disorders and oncological diseases, which may require a diverse range of IR treatments. The aim is to provide a summary of these interventional techniques and highlight the unique considerations necessary for effective pediatric pain management.

PMID:39821652 | DOI:10.1007/s00270-024-03918-3

Bioethics. 2025 Jan 17. doi: 10.1111/bioe.13385. Online ahead of print.

ABSTRACT

Writers have debated whether germline genome-editing is person-affecting or identity-affecting. The difference is thought to be ethically relevant to whether we should choose genome-editing or choose preimplantation genetic diagnosis and embryo selection, when seeking to prevent or produce bad conditions (e.g., cystic fibrosis, or deafness) in the individuals who will grow from the embryo edited or selected. We consider the very recent views of three prominent bioethicists and philosophers who have grappled with this issue. We claim that both sides are right, but that the sense in which genome-editing is person-affecting is less important, morally, when the aim is to have healthy children. Since this is the predominant objective of engaging in embryo selection and genome-editing, and since there are certain risks, at least for now, with genome-editing, it remains better, morally, to engage in embryo selection than genome-editing.

PMID:39821416 | DOI:10.1111/bioe.13385

J Pediatr Endocrinol Metab. 2025 Jan 17. doi: 10.1515/jpem-2024-0566. Online ahead of print.

ABSTRACT

OBJECTIVES: There is limited research on thyroid function in pediatric patients with cystic fibrosis (pwCF). This study aimed to determine the frequency of thyroid dysfunction in children and adolescents with CF and to evaluate iodine deficiency and selenium status in pwCF.

METHODS: Sixty-two CF patients and 62 control subjects were evaluated. The anthropometric measurements, nutritional status, FEV1(Forced-expiratory-volume in 1 s) percentage, thyroid function tests (TSH, FT4, FT3), urinary iodine and selenium levels, hospitalization status in the last six months, antibiotic usage, and colonization status with staphylococcus or pseudomonas were assessed for the cases.

RESULTS: The mean age of the patient group was 10.84 ± 4.04 years. All CF patients were receiving multivitamin supplementation. Malnutrition was present in 50 % of patients, bacterial colonization in 29 %, FEV1 decrease in 38.5 %, subclinical hypothyroidism (SH) in 12.9 %, iodine deficiency in 87 % and exocrine pancreatic insufficiency in 100 %. T3 levels were found to be higher in pwCF. No significant difference was found between malnutrition and FEV1 and urinary iodine and selenium levels. Compared to the control group, pwCF had lower urinary iodine levels.

CONCLUSIONS: To the best of our knowledge, our study is one of the few in the literature to investigate urinary selenium levels alongside iodine in PwCF. Further research is needed to clarify and interpret elevated urinary selenium levels in this context. It was shown that iodine deficiency and the rate of SH were relatively high in pwCF. However, it was still thought that correcting iodine deficiency in these patients could improve thyroid dysfunction associated with CF.

PMID:39817663 | DOI:10.1515/jpem-2024-0566

Scand J Med Sci Sports. 2025 Jan;35(1):e70018. doi: 10.1111/sms.70018.

ABSTRACT

Previous studies in sports science suggested that regular exercise has a positive impact on human health. However, the effects of endurance sports and their underlying mechanisms are still not completely understood. One of the main debates regards the modulation of immune dynamics in high-intensity exercise. As part of the "Run 4 Science" project in Verona, Italy, we conducted a single-cell RNA sequencing analysis on half-marathon amateur runners to investigate the transcriptional dynamics of peripheral blood mononuclear cells following endurance exercise. Blood samples were collected from four participants before and after running a half-marathon to carry out a comprehensive transcriptomic analysis of immune cells at the single-cell level. Our analysis revealed significant alterations in the transcriptional profiles following endurance physical exercise. Modulations in myeloid cells suggested the activation of stress response (6 related pathways, p < 0.04) and pathways related to viral processes (4 related pathways, p < 0.03), while in lymphoid cells they hinted to a shift towards immune activation (24 related pathways, p < 0.01). Additionally, transcriptional changes in platelets point to an activation of the coagulation process (5 related pathways, p < 0.005). Single-cell data was also analyzed following a pseudo-bulk approach (i.e., simulating a bulk RNAseq experiment) to gain further biological insights. Our findings suggest that a pseudo-bulk analysis could offer complementary findings to classical single-cell analysis methods and demonstrate that endurance physical exercise, such as running a half-marathon, induces substantial changes in the transcriptional dynamics of immune cells. These insights contribute to a better understanding of the immune modulation mediated by endurance exercise and may inform future training routines or nutritional guidelines based on individual gene expression levels.

PMID:39817606 | DOI:10.1111/sms.70018

Mol Genet Metab Rep. 2024 Dec 26;42:101182. doi: 10.1016/j.ymgmr.2024.101182. eCollection 2025 Mar.

ABSTRACT

BACKGROUND: Immediately after birth, adaptation to the extrauterine environment includes an upregulation of fatty acid catabolism. Cystic fibrosis and untreated hypothyroidism exert a life-long impact on fatty acid metabolism, but their influence during this transitional period is unknown. Children and adults with cystic fibrosis exhibit unbalanced fatty acid composition, most prominently a relative deficit of linoleic acid. Lipid catabolism is downregulated in hypothyroidism.

METHODS: We analyzed acylcarnitine data in newborn screening blood spot samples from infants with cystic fibrosis, with congenital hypothyroidism, or without congenital disorders. Eight long-chain acylcarnitine species were quantified. Of primary interest was the relative composition of linoleoylcarnitine (C18:2), the acylcarnitine of linoleic acid. Mixed effects modeling was used to determine the impact of disease status on acylcarnitine levels, accounting for possible covariates including birth weight, gestational age, sex and race.

RESULTS: Total long-chain acylcarnitine levels were diminished in newborns with cystic fibrosis and with congenital hypothyroidism. Contrary to expectations, C18:2 composition was elevated in newborns with cystic fibrosis and with congenital hypothyroidism, as compared to those without congenital disorders. Furthermore, higher thyroid-stimulating hormone levels, indicative of more severe hypothyroidism, predicted higher C18:2 composition.

CONCLUSIONS: Decreased total long-chain acylcarnitine concentrations in newborns with cystic fibrosis and congenital hypothyroidism suggest diminished beta-oxidation. However, the unexpected relative increase in C18:2 indicates selective preservation of linoleic acid beta-oxidation in both conditions. This is especially surprising in cystic fibrosis where linoleic acid levels become diminished and suggests that linoleic acid beta-oxidation contributes to the deficiency of linoleic acid in cystic fibrosis.

PMID:39816991 | PMC:PMC11732690 | DOI:10.1016/j.ymgmr.2024.101182