ERJ Open Res. 2025 Jul 7;11(4):00971-2024. doi: 10.1183/23120541.00971-2024. eCollection 2025 Jul.

ABSTRACT

BACKGROUND: Maintaining good cardiopulmonary fitness is crucial for global health in cystic fibrosis (CF), but there is limited knowledge about the longitudinal evolution of fitness measures at young ages, particularly with recent therapeutic advances. We investigated trends in exercise test outcomes in young people with CF and how they are influenced by elexacaftor, tezacaftor and ivacaftor (ETI) and the coronavirus disease 2019 (COVID-19) pandemic.

METHODS: 70 young people with CF (12-20 years old) were included in this retrospective observational single-centre study. We reviewed 177 symptom-limited surveillance cardiopulmonary exercise tests (CPETs) conducted on a cycle ergometer between 2010 and 2024. Longitudinal trends in peak oxygen uptake (V'O2 peak), maximal workload and ventilation were analysed using linear mixed models, separately for periods before and after the COVID-19 pandemic onset and ETI introduction.

RESULTS: In ETI-naive people with CF, V'O2 peak was lower, and the increase from 12 to 20 years was smaller than predicted by validated reference data (p<0.001). 40 people with CF started ETI during the observational period with 46 of 103 tests performed under ETI (median therapy duration 1.6 years, range 0.4-3.9). After ETI introduction, V'O2 peak improved significantly, whereas ventilation and maximal workload were not relevantly affected. ETI approval coincided with the COVID-19 pandemic, during which a steeper decline of V'O2 peak in ETI-naive people with CF was observed. However, this potential confounder did not significantly impact the overall longitudinal improvement in V'O2 peak trajectory following ETI introduction (p<0.05).

CONCLUSION: The longitudinal trend in V'O2 peak progression from adolescence to young adulthood is impaired in people with CF, but the initiation of ETI can have a positive impact on this trajectory.

PMID:40630381 | PMC:PMC12230750 | DOI:10.1183/23120541.00971-2024

Anesthesiology. 2025 Aug 1;143(2):424-443. doi: 10.1097/ALN.0000000000005534. Epub 2025 Jul 8.

ABSTRACT

Diabetes in pregnancy is a common obstetric comorbidity that increases the risks of pregnancy-specific complications. The authors describe in this review how understanding ambulatory use of insulin can impact peripartum anesthesia care. Additionally, they describe the appropriate delivery, dosing, and timing of insulin during birth as relevant for anesthesiologists. They discuss the indications and limitations of technologies such as continuous glucose monitors and insulin pumps in pregnancy, and describe their relevance and appropriate management in the perioperative and peripartum period. Finally, the authors review the unique complication of euglycemic diabetic ketoacidosis and provide appropriate management strategies, as anesthesiologists may be in a position to recognize this complication that could otherwise be overlooked.

PMID:40626748 | PMC:PMC12227212 | DOI:10.1097/ALN.0000000000005534

J Cyst Fibros. 2025 Jul 8:S1569-1993(25)01524-3. doi: 10.1016/j.jcf.2025.07.001. Online ahead of print.

ABSTRACT

BACKGROUND: Despite cystic fibrosis transmembrane conductance (CFTR) modulator therapy that may dramatically alter the course of disease, many people living with cystic fibrosis (PwCF) experience co-occurring symptoms that may be interrelated and may synergistically degrade quality of life. We sought to identify symptom factors, or groups of correlated symptoms, connected by underlying latent variable(s). We then examined demographic and clinical characteristics associated with these groups among PwCF.

METHODS: Using baseline data from a trial of specialist palliative care in PwCF, we assessed symptoms with the Memorial Symptom Assessment Scale-CF. We used exploratory factor analysis followed by confirmatory factor analysis to identify and validate symptom factors. For each factor (using only the symptoms identified in the factor), we then created a binary variable (Symptom Factor Severity) that identified patients as Low versus High Severity, by mean splitting the sum of each patient's severity symptom scores for that factor. Multivariable logistic regression was used to examine associations between demographic and clinical characteristics with each split Symptom Factor Severity score.

RESULTS: Among 262 participants, median age was 33 years, and 78 % were prescribed a CFTR modulator. We identified three symptom factors: respiratory-energy, mood-gastrointestinal irritability, and pain-gastrointestinal dysmotility. High symptom severity in each factor was associated with specific demographic and clinical characteristics.

CONCLUSIONS: CF symptom management strategies have historically focused on single-symptom approaches. Findings from this study may prompt clinicians to consider co-occurring symptoms, and ensure their assessment and management is tailored to the unique experiences of PwCF.

PMID:40628572 | DOI:10.1016/j.jcf.2025.07.001

J Craniomaxillofac Surg. 2025 Jul 7:S1010-5182(25)00226-4. doi: 10.1016/j.jcms.2025.07.003. Online ahead of print.

ABSTRACT

Recurrences following congenital choanal atresia (CA) repair are a particular challenge. This study sought to investigate the underlying causes of recurrences. The study compared 33 primary surgeries (controls, median age 32 months) to 34 revision surgeries (revision group, median age 10 months) performed between 2010 and 2024 at the department of otorhinolaryngology of a German university hospital. Demographic data, surgery time [min], length of hospitalization [nights] and the intraoperatively identified causes of recurrences were analysed. To test for differences between the two groups, the Mann-Whitney-U test was applied. The Chi-square test was used to test for correlations. In the revision group, 88 % (30/34) of the recurrences were attributable to insufficient vomer resections. An additional 12 % (4/34) were attributable to granulations. The revision group was more likely to have a bilateral choanal atresia (p < 0.001). Surgery time was equal in both groups (p = 0.115). Dominantly, insufficient posterior vomer resections, but also granulation tissue growth present the primary causes of recurrence. Adequate resection of the posterior vomer is essential for optimal outcomes and can be achieved with small effort. The implementation of this technique as standard procedure has the potential to reduce the risk of recurrence and enhance the care of patients with CA.

PMID:40628561 | DOI:10.1016/j.jcms.2025.07.003

Cell Rep Med. 2025 Jul 2:102232. doi: 10.1016/j.xcrm.2025.102232. Online ahead of print.

ABSTRACT

Acyl coenzyme A binding protein (ACBP encoded by diazepam binding inhibitor DBI) is involved in non-malignant liver diseases. Here, we show that DBI mRNA and circulating ACBP/DBI levels are increased in patients with hepatocellular carcinoma (HCC). We investigated its role in hepatocarcinogenesis in mice, inhibiting ACBP/DBI by three methods: (1) inducible whole-body or liver-specific knockout of DBI, (2) a point mutation of the ACBP/DBI receptor (GABRG2), and (3) induction of autoantibodies neutralizing ACBP/DBI. ACBP/DBI plays a major pro-carcinogenic role in HCC induced by intrahepatic transplantation of HCC cell lines, transgenic co-expression of the two oncogenes Myc and Ctnnb1, and chronic challenge with a Western-style diet together with either carbon tetrachloride (CCl4) or diethylnitrosamine. ACBP/DBI inhibition normalizes HCC-associated gene expression, reducing oncogenic alterations in cell cycle-, immunomodulatory-, and ferroptosis-regulatory genes. ACBP/DBI inhibition increases HCC responses to PD-1 blockade and sensitizes HCC to the therapeutic induction of ferroptosis. Hence, ACBP/DBI constitutes an actionable target involved in HCC pathogenesis.

PMID:40628264 | DOI:10.1016/j.xcrm.2025.102232

Med Sci Educ. 2025 Feb 27;35(3):1473-1488. doi: 10.1007/s40670-025-02332-9. eCollection 2025 Jun.

ABSTRACT

PURPOSE: Medical education professionals expect artificial intelligence (AI) systems to be an efficient faculty resource for content creation. However, prior findings suggest that machine learning algorithms may exacerbate negative stereotypes and undermine efforts for diversity, equity, and inclusivity. This investigation explores the potential of OpenAI's ChatGPT (OCG) and Microsoft's Bing A.I. Image Creator (MBIC) to perpetuate ethnoracial stereotypes in medical cases.

MATERIALS AND METHODS: A series of medically relevant vignettes and visual representatives were requested from ChatGPT and MBIC for five medical conditions traditionally associated with certain ethnoracial groups: sickle cell anemia, cystic fibrosis, Tay-Sachs disease, beta-thalassemia, and aldehyde dehydrogenase deficiency. Initial prompting, self-prompting, and prompt engineering were iteratively performed to ascertain the extent to which AI outputs for generated vignettes and imagery were mutable or fixed.

RESULTS: The ethnoracial identity in the vignettes of the clinical conditions adhered more closely than described in epidemiologic studies. Following prompt engineering and self-prompting, an increase in diversity was seen. On initial prompting, the most common ethnoracial identity depicted was Caucasian. Secondary prompting resulted in less diversity with higher conformation to the traditionally expected ethnoracial identity.

CONCLUSION: The prevalence of dataset bias and AI's user-dependent learning abilities underscore the importance of human stewardship. The increasing use of AI in generating medical education content, like MCQs, demands vigilant use of such tools to combat the reinforcement of the race-based stereotypes in medicine.

PMID:40625992 | PMC:PMC12228611 | DOI:10.1007/s40670-025-02332-9

Ital J Pediatr. 2025 Jul 7;51(1):212. doi: 10.1186/s13052-025-02018-3.

ABSTRACT

BACKGROUND: Childhood interstitial lung disease (chILD) encompasses a heterogeneous group of rare disorders characterized by respiratory distress, hypoxemia, exercise intolerance, and distinctive radiological findings. Despite the variable age of onset, these conditions often present with overlapping symptoms and variable progression, even with identical genetic mutations. Surfactant protein deficiencies fall under the category of chILD, with Surfactant Protein-C (SP-C) deficiency posing significant diagnostic challenges due to its rarity and the variable severity of clinical presentation.

CASE PRESENTATION: We present the case of a 15-year-old male from Senegal who recently arrived in Italy, presenting with severe respiratory distress and hypoxemia. The patient, born full-term, had a long history of chronic cough, recurrent respiratory distress, and poor growth since early infancy. Upon hospitalization, he tested positive for SARS-CoV-2 and exhibited signs of chronic respiratory failure and severe malnutrition. An extensive diagnostic work-up, including a chest CT scan, revealed small cystic-like air spaces and diffuse ground-glass opacities. Whole-exome sequencing confirmed the diagnosis of SP-C deficiency by identifying a heterozygous missense mutation (c.218t>C, Ile73Thr) in the third exon of the SFTPC gene. Treatment with steroids, azithromycin and hydroxychloroquine was initiated. Despite pharmacological treatments, the patient remained oxygen dependent due to the severity of this condition and required long-term bilevel non-invasive ventilatory support.

CONCLUSIONS: This case provides insight into the natural course of untreated child, specifically SP-C deficiency, enhancing our understanding of its manifestations and progression. The lack of standardized treatments underscores the critical need for increased awareness among physicians of this rare but potentially life-threatening condition, enabling early diagnosis and timely therapeutic interventions.

PMID:40624696 | DOI:10.1186/s13052-025-02018-3

Thorax. 2025 Jul 7:thorax-2025-223460. doi: 10.1136/thorax-2025-223460. Online ahead of print.

NO ABSTRACT

PMID:40623823 | DOI:10.1136/thorax-2025-223460

Thorax. 2025 Jul 7:thorax-2024-222396. doi: 10.1136/thorax-2024-222396. Online ahead of print.

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) is a growing global health crisis and is particularly relevant to people living with chronic lung diseases such as bronchiectasis, cystic fibrosis and chronic obstructive pulmonary disease. These conditions frequently involve acute and chronic bacterial infections, requiring increased antibiotic usage and risk of AMR. Understanding the dynamics of AMR and emerging diagnostic and therapeutic strategies is crucial for optimising patient outcomes in this setting.

AIMS: This review explores the interplay between AMR and chronic bacterial lung infections, examining current understanding of pathogen epidemiology, diagnostic strategies, clinical implications of resistance and the impact of treatments. Future directions in research and therapeutic innovation are also outlined.

NARRATIVE: Key pathogens in chronic lung infections, such as Pseudomonas aeruginosa, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis, exhibit diverse resistance mechanisms and AMR is linked to increased disease severity, exacerbation frequency and mortality, particularly with multidrug-resistant strains. Long-term antibiotic therapies, such as macrolides and inhaled agents, improve clinical outcomes but may drive resistance, necessitating ongoing efforts to understand how they can best be employed. Traditional diagnostic methods, such as culture-based antimicrobial susceptibility testing, often fail to capture the complexity of polymicrobial infections and resistomes. Although advanced techniques like next-generation sequencing and metagenomics are able to identify clinically relevant resistotypes, their development toward clinical utility is still in progress.

CONCLUSIONS: AMR in chronic lung infections represents a dynamic and multifaceted challenge. Novel antibiotics, precision medicine approaches and alternative therapies such as bacteriophages show promise but require further validation. Improved stewardship and individualised treatment strategies are critical for mitigating AMR and enhancing patient outcomes. Collaborative efforts among researchers, clinicians and policy-makers are vital to advancing care and combating this global threat.

PMID:40623822 | DOI:10.1136/thorax-2024-222396

Int Rev Cell Mol Biol. 2025;394:171-196. doi: 10.1016/bs.ircmb.2024.12.011. Epub 2025 Jan 20.

ABSTRACT

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the introduction of numerous drugs to cure this deadly disease, treatment outcomes differ significantly among patients. This differential response has drawn attention to individual patient characteristics, particularly the microbiome. In recent years, the microbiome has garnered significant interest from scientists in various fields including autoimmune, inflammatory, and cancer research. These studies have primarily focused on the composition and diversity of the gut microbiome, pointing out its fundamental effect on the development and progression of diseases such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and lung cancer. Recent findings have also highlighted the impact of the gut microbiome on the efficacy of immunotherapy in lung cancer patients. In this chapter, we will delve into the multifaceted role of microbiome in lung cancer prevention, progression, and treatment outcome.

PMID:40623766 | DOI:10.1016/bs.ircmb.2024.12.011

Proc Natl Acad Sci U S A. 2025 Jul 15;122(28):e2501584122. doi: 10.1073/pnas.2501584122. Epub 2025 Jul 7.

ABSTRACT

The tissue hormone acyl coenzyme A-binding protein (ACBP, encoded by the gene diazepam-binding inhibitor, DBI) has been implicated in various facets of pathological aging. Here, we show that ACBP plasma concentrations are elevated in (close-to-)centenarians (mean ± SD age 99.5 ± 4.5 y) commensurate with their health deterioration, correlating with a reduced glomerular filtration rate and a surge in senescence-associated cytokines. ACBP neutralization by means of a monoclonal antibody (mAb) improved health span in a strain of progeroid mice. In a mouse model of chronic kidney injury induced by cisplatin, anti-ACBP mAb administration counteracted both histopathological and functional signs of organ failure. ACBP inhibition also prevented the senescence of tubular epithelial cells and glomerular podocytes induced by cisplatin or doxorubicin, respectively, as measurable by the immunohistochemical detection of cyclin-dependent kinase inhibitor 1A (CDKN1A, best known as p21). Senescence was also prevented by anti-ACBP mAb treatment in additional mouse models of accelerated aging. This applied to liver damage induced by a combination of high-fat diet and carbon tetrachloride, where hepatic cells become senescent. Moreover, administration of anti-ACBP mAb prevented natural and doxorubicin-accelerated cardiomyocyte senescence. We performed single-nucleus RNA sequencing to study the transcriptome of hearts that had been exposed to doxorubicin and/or anti-ACBP in vivo. In cardiomyocytes, doxorubicin caused an anti-ACBP-reversible dysregulation of mRNAs coding for cardioprotective proteins involved in autophagy, fatty acid oxidation, mitochondrial homeostasis, and oxidative phosphorylation. Altogether, these findings plead in favor of a broad age-promoting effect of ACBP across different organ systems.

PMID:40623176 | DOI:10.1073/pnas.2501584122

mSystems. 2025 Jul 7:e0172224. doi: 10.1128/msystems.01722-24. Online ahead of print.

ABSTRACT

Within-host environments are complex and multidimensional, making it challenging to link the evolutionary responses of colonizing pathogens to causal selective drivers. Loss of quorum sensing (QS) via mutation of the master regulator, lasR, is a common adaptation of Pseudomonas aeruginosa during chronic infections. Here, we use experimental evolution in host-mimicking media to show that loss of QS is constrained by environmental factors associated with host inflammation. Specifically, environments combining oxidative stress and abundant free amino acids limited loss of QS, whereas QS loss was rapid in the absence of oxidative stress, regardless of amino acids. Under oxidative stress, lasR mutations were contingent upon first decoupling regulation of oxidative stress responses from QS via mutations in the promoter region of the primary catalase, katA, or in the oxidative stress regulator, oxyR, enabling maintenance of oxidative stress tolerance. Together, our findings suggest that host inflammatory responses likely delay the loss of QS while colonizers undergo stepwise evolution, first adapting to survive lethal stressors before responding to other nutritional selective drivers that favor loss of QS.

IMPORTANCE: Pseudomonas aeruginosa is a common cause of chronic infections characterized by persistent inflammation. Host inflammatory responses alter within-host environments, including by increasing levels of antimicrobial stressors and releasing free amino acids through proteolysis. Here, we show stepwise adaptation of experimental P. aeruginosa populations to inflammation-like environments, first adapting to survive lethal stress by decoupling oxidative stress responses from quorum sensing (QS), before then adapting to the nutritional conditions, delaying the loss of quorum sensing. These results highlight the power of using laboratory evolution experiments to disentangle the multidimensional selective forces driving pathogen adaptation in complex within-host environments.

PMID:40621905 | DOI:10.1128/msystems.01722-24

J Pediatr Gastroenterol Nutr. 2025 Jul 7. doi: 10.1002/jpn3.70121. Online ahead of print.

ABSTRACT

OBJECTIVE: Pediatric inflammatory bowel diseases (PIBDs), despite being more prevalent in westernized nations, show an increasing incidence worldwide. Accurate evaluation, diagnosis, therapy, and monitoring are mandatory for the adequate management of patients, as is a sensible use of expensive resources, which may be limited in some parts of the world. This limitation often poses challenges to diagnose and treat patients. As the long-term prognosis very much depends on early diagnosis and remission of active disease, it is important to consider reasonable alternatives that may help clinicians to act accordingly within resource constraints, without downgrading previously published guidelines.

METHODS: A group of experts from the "Paediatric IBD Porto Group" of European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) as well as pediatric and adult IBD experts, trained in IBD centers and having working experience in limited-resource settings (LR settings), joined efforts to suggest alternative options in settings where resources are limited, while prioritizing an acceptable cost-effectiveness ratio. Almost all recently published ESPGHAN guidelines and position papers on PIBD were evaluated, and the writing group framed proposals for adaptation in situations with limited access to more expensive resources or tools.

RESULTS: Ninety consensus-based recommendations, derived from the available evidence, were formulated. Diagnostic protocol, biochemical evaluation, imaging and endoscopy, monitoring and options for nutritional, medical and surgical treatment were addressed. Cooperation between professionals and institutions was suggested to improve quality of care and optimize use of available expertise. Patient education, counseling, mental health and transition of care were also addressed.

CONCLUSION: Diagnosis and management of PIBD are complex and costly in medical resources, but some alternative protocols could provide acceptable results and help with accurate diagnosis and management. These recommendations and practice points may offer useful guidance in settings where resources may be limited while still providing good medical practice.

PMID:40621690 | DOI:10.1002/jpn3.70121

Curr Opin Organ Transplant. 2025 Jul 8. doi: 10.1097/MOT.0000000000001238. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: The ischemia-reperfusion injury (IRI) of the bronchial epithelium after lung transplant (LTx) leads to tissue-specific stem cells (TSC) activation, promoting their migration and facilitation of airway remodeling characterized by a chimeric mixture of donor-derived and recipient-derived epithelial cells. This process results in airway epithelial cell chimerism, which we will discuss in this review as having a role in the pathogenesis of chronic lung allograft dysfunction (CLAD) in LTx recipients (LTRs).

RECENT FINDINGS: In LTx, IRI of the airway epithelium can be significant, contributing to cell death and inflammatory processes. TSCs have been implicated in the pathogenesis of CLAD. In cystic fibrosis LTRs where we can differentiate epithelial cells by cystic fibrosis transmembrane conductance regulator (CFTR) function, integration of recipient-derived cells expressing dysfunctional CFTR protein were discovered even years after the LTx, and this chimerism impacted CFTR function. Recent findings also highlight similarities between pulmonary chronic graft-versus-host disease and CLAD. Animal studies have demonstrated that donor-derived epithelial cells can successfully engraft and aid tissue repair.

SUMMARY: Airway epithelial cell chimerism occurs in LTRs because of the normal human bronchial epithelial repairing mechanisms by TSCs that result from the IRI after surgical implantation of donor lungs. Enhancing donor-derived TSCs may offer a promising therapeutic strategy to promote epithelial repair and reduce the risk of CLAD following LTx.

PMID:40620157 | DOI:10.1097/MOT.0000000000001238

Mycopathologia. 2025 Jul 6;190(4):62. doi: 10.1007/s11046-025-00968-0.

ABSTRACT

Chronic colonization by filamentous fungi in patients with cystic fibrosis (pwCF) is linked to declines in lung function and quality of life. To better assess indoor mold exposure, 23 French dwellings of pwCF from CF care centers in Normandy and Maine & Loire, France were visited. Bioaerosols collected using Coriolis® µ and Coriolis® compact biocollectors and dust were cultured on four different media: Potato Dextrose Agar (PDA), Malt Extract Agar (MEA), Sabouraud Chloramphenicol Gentamicin (SCG) and Sabouraud Chloramphenicol Gentamicin Actidione (S +). A total of 164 fungal species were identified (44 in both air and dust, 77 in air only and 43 in dust only), with no significant difference in average species count between air and dust samples (p = 0.353). The Coriolis® µ biocollector yielded significantly higher species recovery and fungal load from air samples compared to the Coriolis® compact biocollector (p < 0.001 and p < 0.0001, respectively). Higher CFU/m3 for Aspergillus, Fusarium, Mucor and Rhizopus were found on MEA, PDA and SCG media compared to S + (p = 0.037, p = 0.005 and p = 0.030, respectively). Alpha diversity was also greater on MEA, PDA and SCG media than on S + medium (p = 0.001, p < 0.0001 for PDA and SCG) and PDA than on MEA (p = 0.008). The distribution of common fungal genera was consistent with literature, except for higher frequencies of Fusarium and Talaromyces in our study. In conclusion, air sampling with the Coriolis® µ biocollector and inoculation on PDA or MEA media is recommended for this type of field study.

PMID:40619550 | DOI:10.1007/s11046-025-00968-0

J Cyst Fibros. 2025 Jul 5:S1569-1993(25)01518-8. doi: 10.1016/j.jcf.2025.06.004. Online ahead of print.

NO ABSTRACT

PMID:40619329 | DOI:10.1016/j.jcf.2025.06.004

J Cyst Fibros. 2025 Jul 4:S1569-1993(25)01520-6. doi: 10.1016/j.jcf.2025.06.006. Online ahead of print.

NO ABSTRACT

PMID:40617775 | DOI:10.1016/j.jcf.2025.06.006

Acad Radiol. 2025 Jul 4:S1076-6332(25)00573-2. doi: 10.1016/j.acra.2025.06.024. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: Hyperpolarized 129Xenon magnetic resonance imaging (MRI) measures the extent of lung ventilation by ventilation defect percent (VDP), but VDP alone cannot distinguish between diseases. Prior studies have reported anecdotal evidence of disease-specific defect patterns such as wedge-shaped defects in asthma and polka-dot defects in lymphangioleiomyomatosis (LAM). Neural network artificial intelligence can evaluate image shapes and textures to classify images, but this has not been attempted in xenon MRI. We hypothesized that an artificial intelligence network trained on ventilation MRI could classify diseases based on spatial patterns in lung MR images alone.

MATERIALS AND METHODS: Xenon MRI data in six pulmonary conditions (control, asthma, bronchiolitis obliterans syndrome, bronchopulmonary dysplasia, cystic fibrosis, LAM) were used to train convolutional neural networks. Network performance was assessed with top-1 and top-2 accuracy, recall, precision, and one-versus-all area under the curve (AUC). Gradient class-activation-mapping (Grad-CAM) was used to visualize what parts of the images were important for classification.

RESULTS: Training/testing data were collected from 262 participants. The top performing network (VGG-16) had top-1 accuracy=56%, top-2 accuracy=78%, recall=.30, precision=.70, and AUC=.85. The network performed better on larger classes (top-1 accuracy: control=62% [n=57], CF=67% [n=85], LAM=69% [n=61]) and outperformed human observers (human top-1 accuracy=40%, network top-1 accuracy=61% on a single training fold).

CONCLUSION: We developed an artificial intelligence tool that could classify disease from xenon ventilation images alone that outperformed human observers. This suggests that xenon images have additional, disease-specific information that could be useful for cases that are clinically challenging or for disease phenotyping.

PMID:40617705 | DOI:10.1016/j.acra.2025.06.024

BMJ Open Respir Res. 2025 Jul 5;12(1):e002488. doi: 10.1136/bmjresp-2024-002488.

ABSTRACT

BACKGROUND: Low body mass index (BMI) is associated with poor prognosis in patients with non-cystic fibrosis (non-CF) bronchiectasis. However, the impact of being overweight or obese on clinical outcomes of these patients remains controversial.

MATERIALS AND METHODS: This retrospective cohort study was conducted using TriNetX. Patients diagnosed with non-CF bronchiectasis between 2012 and 2022 were identified. The eligible population was divided into four groups based on their BM. Propensity score matching (PSM) was used to balance baseline demographic and clinical characteristics between study groups. The primary outcome of interest was all-cause mortality during a 5-year follow-up period.

RESULTS: A total of 14 469 patients were included in the analysis. After PSM, the underweight group exhibited significantly higher all-cause mortality compared with those with a normal BMI (24.3% vs 15.3%; HR 1.83; 95% CI 1.49 to 2.25; p=0.0150). Conversely, both the overweight (16.6% vs 21.4%; HR 0.77; 95% CI 0.68 to 0.88; p=0.0138) and obese groups (16.8% vs 20.2%; HR 0.79; 95% CI 0.71 to 0.87; p=0.0356) demonstrated lower all-cause mortality rates. In addition, consistently higher risks in the underweight group and lower risks in the overweight and obese groups were observed for several critical health outcomes, including the need for critical care service, incidence of pneumonia, tuberculosis or non-tuberculous mycobacterial infection, acute exacerbation of bronchiectasis, acute respiratory failure and ventilator use.

CONCLUSIONS: Being underweight is a risk factor for all-cause mortality in patients with non-CF bronchiectasis and the aforementioned clinical outcomes. Conversely, overweight and obesity are associated with lower all-cause mortality rates and better outcomes.

PMID:40617601 | DOI:10.1136/bmjresp-2024-002488

EBioMedicine. 2025 Jul 4;118:105840. doi: 10.1016/j.ebiom.2025.105840. Online ahead of print.

ABSTRACT

BACKGROUND: Ataxia-telangiectasia (A-T) is a rare multisystem disease characterised by neurodegenerative cerebellar ataxia, lung disease, immune deficiency, high cancer risk, and mitochondrial dysfunction. A-T cells demonstrate defective endoplasmic reticulum-mitochondrial connectivity disrupting calcium homoeostasis and mitochondrial fusion, which are corrected in vitro by the triheptanoin metabolite, heptanoate.

METHODS: We performed a Phase 2a/b trial of triheptanoin with a three-arm placebo-controlled dose-escalation design. Doses escalated at 2-month intervals for 12 months in the sequence 0%, 10%, 20%, 35% of calculated caloric intake. The primary outcome was cell death in respiratory epithelial cells. Key secondary outcomes included scales for assessment and rating of ataxia (SARA), international cooperative ataxia rating scale (ICARS), speech and swallowing function, and novel biomarker discovery.

FINDINGS: 31 participants with A-T were enrolled aged from 4 to 37 years (median 16-years). For the maximum dose vs. placebo or no dose, significant improvements was observed for the primary outcome percent nasal cell death (mean difference (MD) = -9.7%, 95% confidence interval (CI) -16.0, 4.6). The SARA subscale kinetic function improved (MD = -5.8, 95% CI -10.4, -1.2), as did ICARS subscales gait (MD = -0.5, 95% CI -0.9, -0.1) and fine motor disturbance (MD = -2.7, 95% CI -4.3, -1.1). Speech intelligibility (MD = -12.8, 95% CI -21.2, -4.3) and swallowing safety (-0.9, 95% CI -1.6, -0.3) improved. Adverse events including abdominal pain, nausea, vomiting, and diarrhoea, requiring dose capping at 20%, were observed in 12 (38%) participants.

INTERPRETATION: Improvements in mitochondrial function in A-T cells in vivo in patients occurred after triheptanoin. The biomarkers neurofilament light chain and interferon signature stimulated gene scores may allow for monitoring of disease progression and treatment response.

FUNDING: Funded by Medical Researcher Futures Fund Australia (GA89314), The University of Queensland, Wesley Research Institute, and BrAshA-T.

PMID:40616902 | DOI:10.1016/j.ebiom.2025.105840