Study Design: In a treatment-control animal study expansion thoracoplasty (ET) was performed in a juvenile rabbit model of thoracic insufficiency syndrome (TIS) and benefits to thoracic development and respiratory function quantified. Rabbits treated early versus late were compared to age-matched normal and disease control rabbits through to skeletal maturity.
Objective: Evaluate (1) how ET changes the natural TIS disease trajectory and (2) how timing of ET affects changes in spine growth, lung growth, and respiratory mechanics.
Summary Of Background Data: Pulmonary growth potential is thought to diminish with age; thus, early therapeutic intervention may increase pulmonary growth in children with TIS. However, no direct empirical evidence exists to support this treatment paradigm.
Methods: Convex left scoliosis and resultant TIS was induced in 3-week-old rabbits via surgical rib tethering. We compare the efficacy of ET performed at 7 weeks and expanded at 11 weeks (early, n = 7) versus only at 11 weeks of age (late, n = 7) in preserving lung growth and respiratory function relative to normal (n = 8) and disease (n = 10) rabbits. Sequential computed tomography images and pulmonary function testing was performed to quantify spine curvature, lung growth, and respiratory volumes. At 28 weeks of age chest wall elastance was measured in vivo then acinar complexity analyzed histologically via radial alveolar counts.
Results: ET performed early or late altered the predicted trajectory of spine deformity, pulmonary growth inhibition, and respiratory dysfunction seen in disease rabbits. Growth was not significantly different between early and late rabbits and post-treatment gains remained below those of age-matched normal rabbits. Chest wall elastance was impaired by ET and more so in early rabbits, there were no differences in pulmonary elastance.
Conclusion: ET interrupted the natural progression of deformity and pulmonary hypoplasia associated with spine curvature in disease rabbits. However, growth benefits are only seen in cases of the most severe initial deformity and must be balanced against the further impairment to chest wall function associated with repetitive surgery.
Level Of Evidence: N/A.
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http://dx.doi.org/10.1097/BRS.0000000000002573 | DOI Listing |
Iran J Basic Med Sci
January 2025
Department of Medical Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Objectives: Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that have vital roles in activating further immune responses. However, due to their tumor-induced diversity, we decided to examine ILCs, T cells, and the associated cytokines in mouse models of breast cancer.
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Tob Induc Dis
January 2025
Institute of Medical Science, University of Toronto, Toronto, Canada.
Introduction: There is substantial interest in the association of vaping e-cigarettes with the risk of cancer. We analyzed this risk in different populations by updating the Kings College London (KCL) review to include the period between July 2021 and December 2023.
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Pediatr Pulmonol
January 2025
Department of Clinical Research, Faculty of Health sciences, University of Southern Denmark, Odense, Denmark.
Introduction: A main feature of CDH is lung hypoplasia and the related presentation of pulmonary hypertension and cardiac dysfunction. Multiple factors influence pulmonary status after CDH: degree of hypoplasia, ventilator-induced injury, altered growth and development of pulmonary structures, reduced diaphragm function and chest wall abnormalities. The evolution of pulmonary sequela in this population is still unclear.
View Article and Find Full Text PDFRespir Res
January 2025
Department for Pulmonary Medicine, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Introduction: Fibrotic cocktail (FC) is a combination of pro-fibrotic and pro-inflammatory mediators that induces early fibrotic changes in organotypic lung models. We hypothesised that transforming growth factor beta 1 (TGF-β1) alone induces a pro-fibrotic effect similar to FC. Our aim was to compare the pro-fibrotic effects of TGF-β1 with FC in human precision-cut lung slices (PCLS).
View Article and Find Full Text PDFNat Biotechnol
January 2025
Department of Biomedicine, University of Basel, Basel, Switzerland.
Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.
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