Cystic Fibrosis
The effect of elexacaftor-tezacaftor-ivacaftor on liver stiffness in children with cystic fibrosis
J Pediatr Gastroenterol Nutr. 2025 Apr 23. doi: 10.1002/jpn3.70050. Online ahead of print.
ABSTRACT
OBJECTIVES: Cystic fibrosis hepato-biliary involvement (CFHBI) is a common comorbidity in patients with CF and is associated with increased morbidity and mortality. The effect of the new and highly potent CF transmembrane conductance regulator modulator therapy, elexacaftor-tezacaftor-ivacaftor (ETI), on CFHBI, is still unclear. This study aimed to investigate the impact of ETI on liver stiffness in children with CF, as measured using two-dimensional (2D) shear wave elastography (SWE).
METHODS: Twenty-one children with CF were included in this retrospective study at the CF centre, Skåne University Hospital, Lund, Sweden. Twelve children of our cohort had CFHBI; none had advanced CF liver disease. 2D SWE data from annual assessments, clinical data and liver enzymes were analysed.
RESULTS: We found a significant reduction in liver stiffness after starting treatment with ETI in the total cohort. This reduction in liver stiffness could even be seen in children with CFHBI. Liver enzymes were within the normal range in both pre- and post-ETI therapy in the total cohort. In children with CFHBI, a decline in aspartate aminotransferase activity was observed after ETI was initiated. Lung function and lung clearance index improved significantly after ETI treatment commenced.
CONCLUSION: ETI treatment could positively affect CFHBI in children with CF, as demonstrated by reduced liver stiffness during treatment.
PMID:40264362 | DOI:10.1002/jpn3.70050
Non-viral mRNA delivery to the lungs
Biomater Sci. 2025 Apr 23. doi: 10.1039/d5bm00322a. Online ahead of print.
ABSTRACT
The rapid advancement of mRNA therapeutics, exemplified by COVID-19 vaccines, underscores the transformative potential of non-viral delivery systems. However, achieving efficient and targeted mRNA delivery to the lungs remains a critical challenge due to biological barriers such as pulmonary mucus, nanoparticle instability, and off-target accumulation particularly in the liver. Addressing these challenges is crucial for advancing treatments for respiratory diseases, including cystic fibrosis, primary ciliary dyskinesia, and lung cancers. This review highlights emerging strategies to enhance lung-targeted mRNA delivery, focusing on lipid nanoparticles, polymeric nanoparticles, lipid-polymer hybrids, and peptide/protein conjugates. By discussing advances in bioinspired design and nanoparticle reformulation, this review provides a roadmap for overcoming current delivery limitations and accelerating the clinical translation of lung-targeted mRNA therapies.
PMID:40264303 | DOI:10.1039/d5bm00322a
Proteostasis landscapes of cystic fibrosis variants reveal drug response vulnerability
Proc Natl Acad Sci U S A. 2025 Apr 29;122(17):e2418407122. doi: 10.1073/pnas.2418407122. Epub 2025 Apr 22.
ABSTRACT
Cystic fibrosis (CF) is a lethal genetic disorder caused by variants in CF transmembrane conductance regulator (CFTR). Many variants are treatable with correctors, which enhance the folding and trafficking of CFTR. However, approximately 3% of persons with CF harbor poorly responsive variants. Here, we used affinity purification mass spectrometry proteomics to profile the protein homeostasis (proteostasis) changes of CFTR variants during correction to assess modulated interactions with protein folding and maturation pathways. Responsive variant interactions converged on similar proteostasis pathways during correction. In contrast, poorly responsive variants subtly diverged, revealing a partial restoration of protein quality control surveillance and partial correction. Computational structural modeling showed that corrector VX-445 failed to confer enough NBD1 stability to poor responders. NBD1 secondary stabilizing mutations rescued poorly responsive variants, revealing structural vulnerabilities in NBD1 required for treating poor responders. Our study provides a framework for discerning the underlying protein quality control and structural defects of CFTR variants not reached with existing drugs to expand therapeutics to all susceptible CFTR variants.
PMID:40261935 | DOI:10.1073/pnas.2418407122
Achromobacter spp.: Emerging pathogens in the cystic fibrosis lung
PLoS Pathog. 2025 Apr 22;21(4):e1013067. doi: 10.1371/journal.ppat.1013067. eCollection 2025 Apr.
NO ABSTRACT
PMID:40261841 | DOI:10.1371/journal.ppat.1013067
New Pseudomonas infections drive Pf phage transmission in CF airways
JCI Insight. 2025 Apr 22:e188146. doi: 10.1172/jci.insight.188146. Online ahead of print.
ABSTRACT
Pf bacteriophages, lysogenic viruses that infect Pseudomonas aeruginosa (Pa), are implicated in the pathogenesis of chronic Pa infections; phage-infected (Pf+) strains are known to predominate in people with cystic fibrosis (pwCF) who are older and have more severe disease. However, the transmission patterns of Pf underlying the progressive dominance of Pf+ strains are unclear. In particular, it is unknown whether phage transmission commonly occurs horizontally between bacteria via viral particles within the airway or if Pf+ bacteria are mostly acquired via de novo Pseudomonas infections. Here, we studied Pa genomic sequences from 3 patient cohorts totaling 662 clinical isolates from 105 pwCF. We identified Pf+ isolates and analyzed transmission patterns of Pf within patients between genetically similar groups of bacteria called "clone types". We found that Pf was predominantly passed down vertically within Pa clone types and rarely via horizontal transfer between clone types within the airway. Conversely, we found extensive evidence of Pa de novo infection by a new, genetically distinct Pf+ Pa. Finally, we observed that clinical isolates showed reduced activity of the type IV pilus and reduced susceptibility to Pf in vitro. These results cast new light on the transmission of virulence-associated phages in the clinical setting.
PMID:40261708 | DOI:10.1172/jci.insight.188146
The potentiator ivacaftor is essential for pharmacological restoration of F508del-CFTR function and mucociliary clearance in cystic fibrosis
JCI Insight. 2025 Apr 22:e187951. doi: 10.1172/jci.insight.187951. Online ahead of print.
ABSTRACT
Pharmacological rescue of F508del-CFTR by the triple combination CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) leads to unprecedented clinical benefits in patients with cystic fibrosis (CF), however, previous studies in CF primary human airway epithelial cultures demonstrated that chronic treatment with the potentiator ivacaftor can render the F508del protein unstable thus limiting restoration of CFTR chloride channel function. However, quantitative studies of this unwanted effect of ivacaftor on F508del channel function including dependency on cell culture conditions remain limited and the impact of chronic ivacaftor exposure on restoration of mucociliary clearance that is impaired in patients with CF has not been studied. In patient-derived primary nasal epithelial cultures, we found that different culture conditions (UNC-ALI medium vs. PneumaCult medium) have profound effects on ETI-mediated restoration of F508del-CFTR function. Chronic treatment with ivacaftor as part of ETI triple therapy limited the rescue of F508del-CFTR chloride channel function when CF nasal epithelial cultures were grown in UNC-ALI medium, but not in PneumaCult medium. In PneumaCult medium, both chronic and acute addition of ivacaftor as part of ETI treatment led to constitutive CFTR-mediated chloride secretion in the absence of exogenous cAMP-dependent stimulation. This constitutive CFTR-mediated chloride secretion was essential to improve viscoelastic properties of the mucus layer and to restore mucociliary transport on CF nasal epithelial cultures. Furthermore, nasal potential difference measurements in patients with CF showed that ETI restored constitutive F508del-CFTR activity in vivo. These results demonstrate that ivacaftor as a component of ETI therapy is essential to restore mucociliary clearance and suggest that this effect is facilitated by its constitutive activation of F508del channels following their folding-correction in patients with CF.
PMID:40261705 | DOI:10.1172/jci.insight.187951
The 1-minute sit-to-stand test in children with cystic fibrosis: cardiorespiratory responses and correlations with aerobic fitness, nutritional status, pulmonary function, and quadriceps strength
Physiother Theory Pract. 2025 Apr 22:1-8. doi: 10.1080/09593985.2025.2494114. Online ahead of print.
ABSTRACT
OBJECTIVE: To characterize physiological responses to a 1-minute sit-to-stand test (STS) and assess correlations with cardiopulmonary exercise test (CPET) variables, nutritional status, pulmonary function, and quadriceps muscle strength in cystic fibrosis (CF) patients.
METHODS: Subjects aged 6-18 years with a genetic diagnosis of CF were enrolled in this cross-sectional study. After collecting demographic, anthropometric, and clinical data the following tests were performed: pulmonary function (spirometry), aerobic fitness (CPET), STS, and isometric quadriceps muscle strength (hand-held dynamometry). Data collection was performed on the same day.
RESULTS: The study sample comprised 17 children (9.8 ± 1.6 years) and adolescents (13.7 ± 1.5 years) with a mean forced expiratory volume in one second (FEV1) of - 0.80 ± 1.61 (z-score). In the CPET, peak exercise oxygen consumption (VO2peak) was 35.1 ± 4.2 mL.kg-1.min-1, while in the STS mean number of repetitions was 32.5 ± 6.2 and total work (repetitions × body mass) was 1326.9 ± 379.6. At peak exercise, CPET elicited higher heart rate (p = .001) and subjective sensation of dyspnea (p = .001) compared to STS, though no significant differences were observed in peripheral oxygen saturation. Moderate and significant correlations were identified between total workload (CPET) and repetitions adjusted for body weight (r = 0.684; p = .002) and between STS repetitions and muscle strength corrected for body weight (r = 0.531; p = .034). No significant correlations were found with nutritional status (BMI), pulmonary function (FEV1), or other aerobic fitness variables (VO2 at ventilatory threshold or VO2peak).
CONCLUSION: In children and adolescents with CF, compared to CPET, the STS test elicits a submaximal cardiorespiratory response that is mostly dependent on quadriceps muscle strength.
PMID:40260956 | DOI:10.1080/09593985.2025.2494114
CFTR acts as a potential therapeutic target for attention deficit-hyperactivity disorder
Sci Rep. 2025 Apr 21;15(1):13767. doi: 10.1038/s41598-025-98900-5.
ABSTRACT
The prevalence of attention deficit-hyperactivity disorder (ADHD) symptoms among individuals with cystic fibrosis (CF) is significantly elevated compared to the general population. Given that the cystic fibrosis transmembrane conductance regulator (CFTR) is the causative gene for cystic fibrosis, this raises the possibility of CFTR playing a crucial role in ADHD. In our study, three heterozygous missense variants (p.E217G, p.F316L, and p.T1220I) were detected in the CFTR gene, which co-segregate with ADHD in two consanguineous families, impacting a total of six family members. Through the utilization of a zebrafish model, it was observed that the cftr knockout line exhibited behaviors akin to hyperactivity, impulsivity, and attention deficits, mirroring the symptoms seen in human ADHD patients. Single-cell RNA sequencing performed on 7 dpf larvae revealed clusters of neuron cells that exhibited sensitivity to cftr, particularly noting a reduction in the number of dopaminergic neuron cells within the cftr mutant fish. Additionally, bulk RNA sequencing and proteomic analysis conducted during the early gastrulation stage demonstrated abnormal expression levels of nervous system genes. Notably, we attempted to employ CFTR modulators Lumacaftor (VX-809) and Ivacaftor (VX-770) to ameliorate the ADHD zebrafish model (generated via per1b mutant), and it was found that enhanced CFTR activity could mitigate ADHD-like behaviors. In summary, our findings shed light on the potential involvement of CFTR in the pathogenesis of ADHD and pave the way for exploring novel diagnostic approaches and therapeutic strategies for ADHD by targeting CFTR.
PMID:40258939 | DOI:10.1038/s41598-025-98900-5
Decoding the role of extracellular vesicles in pathogenesis of cystic fibrosis
Mol Cell Pediatr. 2025 Apr 21;12(1):5. doi: 10.1186/s40348-025-00190-4.
ABSTRACT
BACKGROUND: Intercellular communication is a critical process that ensures cooperation between distinct cell types and maintains homeostasis. In the past decades, extracellular vesicles (EVs) have been recognized as key components in cell-to-cell communication. These EVs carry multiple factors such as active enzymes, metabolites, nucleic acids and surface molecules that can alter the behavior of recipient cells. Thus, the role of EVs in exacerbating disease pathology by transporting inflammatory mediators, and other molecular signals that contribute to chronic inflammation and immune dysregulation in various diseases including cystic fibrosis (CF) is well documented.
MAIN BODY: CF is a genetic disorder characterized by chronic inflammation and persistent infections, primarily affecting the respiratory system. This review explores the multifaceted roles of EVs in CF lung disease, focusing on their biogenesis, cargo, and contributions to disease progression. It is well known that CF results from mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene, leading to defective ion transport, thick mucus secretion, and a propensity for bacterial infections. However, it has been observed that EVs derived from CF patients carry altered molecular cargo, including proteins, lipids, RNA, and DNA, which can exacerbate these conditions by promoting inflammation, and modulating immune responses. Beyond their pathogenic roles, EVs also hold significant therapeutic potential. Their natural ability to transfer bioactive molecules positions them as promising vectors for delivering therapeutic agents, such as gene therapy constructs and anti-inflammatory compounds. Accordingly, a study has shown that these EVs can act as a carrier molecule for transport of functional CFTR mRNA, helping to restore proper chloride ion channel function by correcting defective CFTR proteins in affected cells.
CONCLUSION: This review aims to summarize the role of EVs and their molecular cargo in pathogenesis of CF lung disease via modulation of intracellular signaling leading to persistent inflammation and increased disease severity. We also explored the mechanisms of EV biogenesis, cargo selection, and their effects on recipient cells which may provide novel insights into CF pathogenesis and open new avenues for EV-based therapies aimed at improving disease management.
PMID:40257719 | DOI:10.1186/s40348-025-00190-4
Addressing Gaps in Asthma Management During Childbearing age and Pregnancy: Insights from a Survey of Italian Physicians and Patients
J Asthma. 2025 Apr 21:1-14. doi: 10.1080/02770903.2025.2494222. Online ahead of print.
ABSTRACT
BACKGROUND: Asthma is a common condition among women of childbearing age, requiring careful management, particularly during pregnancy. Despite existing guidelines, significant gaps remain in asthma management during pregnancy, notably for women with moderate-to-severe asthma.
AIM: This study aimed to explore the awareness, limitations, and challenges of asthma management during childbearing age and pregnancy from both asthmatic women (AW) and physician perspectives in Italy. Additionally, it sought to identify unmet needs and collect real-life experiences from Italian centers specialized in severe asthma care.
METHODS: An anonymous online survey was disseminated through scientific networks and patient associations. Separate questionnaires were developed for doctors and AW by a task force of specialists.
RESULTS: 76 doctors and 54 AW completed the survey, with 70% of AW reporting moderate-to-severe asthma. While most physicians had experience managing asthma in pregnancy, 40% lacked systematic collaboration with gynecologists recognizing the need for integrated care. Despite guidelines supporting asthma medication continuity, 60% of doctors reported discontinuing treatments due to perceived risks. However, surveyed AW generally expressed greater confidence in medication safety. Physicians and AW highlighted the lack of pre-pregnancy counseling, with 55% of AW reporting they had never discussed pregnancy plans when starting asthma treatment. Both groups emphasized the need for improved interdisciplinary collaboration and structured asthma care pathways during pregnancy.
CONCLUSIONS: This study reveals significant gaps in asthma management for women of childbearing age and during pregnancy, especially those with moderate-to-severe asthma. Improving outcomes requires better education for patients and healthcare providers, along with a structured multidisciplinary network.
PMID:40257168 | DOI:10.1080/02770903.2025.2494222
Anti-infectives in Pediatric Patients with Cystic Fibrosis: A Comprehensive Review of Population Pharmacokinetic Analyses
Clin Pharmacokinet. 2025 Apr 21. doi: 10.1007/s40262-025-01505-4. Online ahead of print.
ABSTRACT
Pulmonary complications are the leading cause of morbidity and mortality in pediatric patients with cystic fibrosis. Altered pharmacokinetic parameters in this population, as well as high inter- and intra-individual variability, complicate the optimization of anti-infective treatments. In this review, we aim to summarize and describe all anti-infective population pharmacokinetic (popPK) models applied to pediatric populations with cystic fibrosis. Our objectives were to identify the most-reported structural models and retained covariates and to compare the dosing regimens used in clinical routine with those recommended in literature and guidelines. A literature search was done through the PubMed database from inception to August 2024. Studies were retained only if they complied with the inclusion and exclusion criteria. The review included 21 popPK models covering the pharmacokinetic profiles of eight different molecules. Among these, five are recommended antibiotics for treating pulmonary infections in patients with cystic fibrosis. All models incorporated body composition and/or renal function measures as covariates in their pharmacokinetic parameter equations. Standard dosing regimens in the studies were consistent with guidelines and literature recommendations. This is the first review summarizing and describing all anti-infective popPK models in pediatric patients with cystic fibrosis. Improved estimation of pharmacokinetic parameters and a clearer understanding of variability sources will enhance the optimization of antibiotic treatment in clinical practice. Finally, the impact of new targeted therapies on the management of this population will have to be closely monitored in the years ahead.
PMID:40254714 | DOI:10.1007/s40262-025-01505-4
The role of islet CFTR in the development of cystic fibrosis-related diabetes: A semi-systematic review
J Cyst Fibros. 2025 Apr 19:S1569-1993(25)00772-6. doi: 10.1016/j.jcf.2025.04.006. Online ahead of print.
ABSTRACT
BACKGROUND: Cystic fibrosis related diabetes (CFRD) is the most common comorbidity of cystic fibrosis (CF) still, its pathogenesis is poorly understood. Recent studies have suggested that although pancreatic insufficiency is an important explanation for CFRD development, inherent pancreatic islet cell dysfunction may play a role. This study aimed to systematically compile current data regarding the impact of pancreatic islet cell dysfunction on the development of CFRD.
METHODS: A systematic search was conducted in PubMed and Embase. The resulting articles were screened for relevant experimental design and outcomes. Articles underwent data extraction and quality assessment before compilation and analysis of the results.
RESULTS: A total of 268 articles were initially screened and 19 studies conducted between 2006-2022 were finally included in this review. Half of the studies in human tissue and most of the studies in animal tissue could detect CFTR in the islets. Similarly, half of the publications in human islets and most studies in animal islets detect decreased insulin secretion with inhibition/mutation of CFTR.
CONCLUSIONS: The literature on the role of islet CFTR is contradictory. However, a pattern emerges where CFTR loss-of-function mutations have the potential to negatively affect islet cell function in a way that, together with previously described exocrine damage occurring in CF, could play a part in the development of CFRD.
PMID:40254519 | DOI:10.1016/j.jcf.2025.04.006
A host-pathogen metabolic synchrony that facilitates disease tolerance
Nat Commun. 2025 Apr 19;16(1):3729. doi: 10.1038/s41467-025-59134-1.
ABSTRACT
Disease tolerance mitigates organ damage from non-resolving inflammation during persistent infections, yet its underlying mechanisms remain unclear. Here we show, in a Pseudomonas aeruginosa pneumonia mouse model, that disease tolerance depends on the mitochondrial metabolite itaconate, which mediates cooperative host-pathogen interactions. In P. aeruginosa, itaconate modifies key cysteine residues in TCA cycle enzymes critical for succinate metabolism, inducing bioenergetic stress and promoting the formation biofilms that are less immunostimulatory and allow the bacteria to integrate into the local microbiome. Itaconate incorporates into the central metabolism of the biofilm, driving exopolysaccharide production-particularly alginate-which amplifies airway itaconate signaling. This itaconate-alginate interplay limits host immunopathology by enabling pulmonary glutamine assimilation, activating glutaminolysis, and thereby restrain detrimental inflammation caused by the inflammasome. Clinical sample analysis reveals that P. aeruginosa adapts to this metabolic environment through compensatory mutations in the anti-sigma-factor mucA, which restore the succinate-driven bioenergetics and disrupt the metabolic synchrony essential for sustaining disease tolerance.
PMID:40253414 | DOI:10.1038/s41467-025-59134-1
Remote monitoring of cystic fibrosis lung disease in children and young adults
J Cyst Fibros. 2025 Apr 18:S1569-1993(25)00766-0. doi: 10.1016/j.jcf.2025.03.670. Online ahead of print.
ABSTRACT
AIM: Cystic fibrosis (CF) care increasingly demands flexible and personalised approaches, particularly with the growing role of telemedicine in disease management. This study aimed to evaluate the use of home-based spirometry and antibiotic monitoring for assessing lung function trends and treatment patterns in individuals with CF.
METHOD: Individuals aged 0-25 years from seven Swedish CF centres participated in 12 months of routine CF care, digitally recording antibiotic usage and performing home spirometry (aged ≥5 years). Home spirometry sessions were graded according to ATS/ERS criteria, with A-C representing high-quality sessions. Longitudinal FEV1 trends from home and hospital spirometry were analysed using linear mixed effects models, adjusting for clinical stability.
RESULTS: Of 126 invited participants, 110 were enrolled and followed for a median (range) duration of 12 months (9-17). A total of 779 usable home spirometry sessions were conducted, with 388 sessions (50 %) from 80 out of 95 (84 %) participants aged ≥5 years graded as high-quality. Mean (95 % CI) FEV1 was (86-92 %) for home spirometry and 88 % (85-90 %) for hospital spirometry. After adjusting for clinical stability and including only high-quality home spirometry data, the mean difference was 0.6 % (-3.8 %-5.0 %, p=0.78). The mean annual rate of FEV1 decline was -0.48 % (-1.29-0.32 %) for home spirometry and -0.18 % (-0.77-0.41 %) for hospital spirometry, with no statistically significant difference.
CONCLUSION: High-quality home spirometry measurements, adjusted for clinical stability and antibiotic usage, may provide lung function levels and trends closely comparable to hospital spirometry.
PMID:40253216 | DOI:10.1016/j.jcf.2025.03.670
Early life inflammation in CF: can it be reversed by CFTR modulators?
Thorax. 2025 Apr 18:thorax-2025-223225. doi: 10.1136/thorax-2025-223225. Online ahead of print.
NO ABSTRACT
PMID:40250987 | DOI:10.1136/thorax-2025-223225
Experimental investigation of hematological toxicity after radiation therapy combined with immune checkpoint inhibitors
Int J Radiat Oncol Biol Phys. 2025 Apr 16:S0360-3016(25)00372-4. doi: 10.1016/j.ijrobp.2025.04.008. Online ahead of print.
ABSTRACT
PURPOSE: Combining immune checkpoint inhibitors (ICIs) with radiation therapy (RT) has led to significant advancements in cancer treatment. However, evidence from clinical and experimental studies suggests that this combination may increase hematopoietic and lymphatic toxicity. This study aims to investigate the effects of the concurrent application of ICIs (anti-PD-1 and anti-CTLA-4) on radiation-induced hematopoietic and lymphatic injuries under standardized and controlled experimental conditions.
MATERIALS AND METHODS: We utilized various experimental models in C57BL/6 and BALB/c mice to evaluate the impact of ICIs combined with RT on the hematopoietic system. These models involved different RT doses, regimens, and target sites in both healthy and tumor-bearing mice.
RESULTS: Our findings showed that the concurrent use of ICIs did not meaningfully affect post-RT pancytopenia kinetics or the regeneration of specific blood cell lineages over time. Consistently, combining RT with ICIs did not significantly enhance DNA damage in immune cells within the bloodstream. This outcome was comparable across different RT doses, regimens, and target sites and was reproducible in both tumor-bearing and non-tumor-bearing mice. Additionally, there were no significant increases in late side effects, including reductions in bone marrow cell counts or megakaryocyte numbers, after combined radioimmunotherapy.
CONCLUSION: These findings suggest that combining ICIs with RT does not exacerbate hematological toxicity. This information is valuable for interpreting adverse events in clinical trials involving radioimmunotherapy and for predicting potential hematological side effects in cancer patients receiving these treatments.
PMID:40250771 | DOI:10.1016/j.ijrobp.2025.04.008
From geroscience to precision geromedicine: Understanding and managing aging
Cell. 2025 Apr 17;188(8):2043-2062. doi: 10.1016/j.cell.2025.03.011.
ABSTRACT
Major progress has been made in elucidating the molecular, cellular, and supracellular mechanisms underlying aging. This has spurred the birth of geroscience, which aims to identify actionable hallmarks of aging. Aging can be viewed as a process that is promoted by overactivation of gerogenes, i.e., genes and molecular pathways that favor biological aging, and alternatively slowed down by gerosuppressors, much as cancers are caused by the activation of oncogenes and prevented by tumor suppressors. Such gerogenes and gerosuppressors are often associated with age-related diseases in human population studies but also offer targets for modeling age-related diseases in animal models and treating or preventing such diseases in humans. Gerogenes and gerosuppressors interact with environmental, behavioral, and psychological risk factors to determine the heterogeneous trajectory of biological aging and disease manifestation. New molecular profiling technologies enable the characterization of gerogenic and gerosuppressive pathways, which serve as biomarkers of aging, hence inaugurating the era of precision geromedicine. It is anticipated that, pending results from randomized clinical trials and regulatory approval, gerotherapeutics will be tailored to each person based on their genetic profile, high-dimensional omics-based biomarkers of aging, clinical and digital biomarkers of aging, psychosocial profile, and past or present exposures.
PMID:40250404 | DOI:10.1016/j.cell.2025.03.011
Intraluminal causes of mechanical small bowel obstruction: CT findings and diagnostic approach
Eur J Radiol. 2025 Apr 14;187:112115. doi: 10.1016/j.ejrad.2025.112115. Online ahead of print.
ABSTRACT
Intraluminal causes of small bowel obstruction (SBO) are less common than mural or extrinsic etiologies. This review categorizes intraluminal causes of SBO into four broad categories to provide a diagnostic framework for radiologic interpretation: 1) ingested contents, 2) bowel stasis, 3) inflammatory causes, and 4) neoplasms. Ingested materials can result in SBO when individual or accumulated contents are too large to pass, such as in the case of foreign bodies or bezoars. Bowel stasis causing SBO can be secondary to abnormal bowel function, such as in cystic fibrosis, reduced transit of contents at sites of narrowing such as surgical anastomoses, or the formation of enteroliths in diverticula which may subsequently dislodge and result in luminal obstruction. Inflammatory causes of SBO include strictures or fistulas that allow foreign bodies (such as gallstones) formed outside the bowel to enter the bowel lumen and cause obstruction. Finally, neoplasms can present as endophytic masses that occlude the bowel lumen through a ball-valve mechanism or serve as a lead point for intussusception. Recognizing the imaging features that are suggestive of intraluminal SBO is critical for accurate diagnosis and timely patient care.
PMID:40250005 | DOI:10.1016/j.ejrad.2025.112115
Phosphatidylinositol 5-Phosphate-Loaded Apoptotic Body-Like Liposomes for Mycobacterium abscessus Infection Management in Patients With Cystic Fibrosis
J Infect Dis. 2025 Apr 18:jiaf124. doi: 10.1093/infdis/jiaf124. Online ahead of print.
ABSTRACT
The study investigates therapeutic strategies for managing chronic Mycobacterium abscessus infections, particularly in people with cystic fibrosis (PWCF) who are ineligible for standard elexacaftor, tezacaftor, ivakaftor (ETI) treatments. Apoptotic body-like liposomes loaded with phosphatidylinositol 5-phosphate (ABL/PI5P) were tested in vitro in M. abscessus-infected macrophages from PWCF as potential treatment. ABL/PI5P reduced intracellular bacterial viability and showed enhanced effects on a M. abscessus clinical strain when combined with amikacin. Notably, ABL/PI5P was effective on macrophages from PWCF not receiving ETI therapy. The findings suggest ABL/PI5P liposomes as a promising alternative or adjunct therapy, especially for those who cannot access ETI treatment, warranting further clinical investigation.
PMID:40249250 | DOI:10.1093/infdis/jiaf124