Root cause determination of intraperitoneal catheter obstructions: Insulin amyloid aggregates vs foreign body reaction
| Autor: | Jia He, Diane J. Burgess, Jerome Place, Eric Renard, Eleazere Cem-Duranty, Xiaoyi Wang, Don Cohen, Peter C. Lord, Bing Gu, Gowtham Yenduri |
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| Přispěvatelé: | University of Connecticut (UCONN), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Catheter Obstruction
Insulin pump Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Continuous intraperitoneal insulin infusion Amyloid medicine.medical_treatment [SDV]Life Sciences [q-bio] Drug-device combination Pharmaceutical Science 02 engineering and technology 03 medical and health sciences Peritoneal cavity Insulin Infusion Systems Foreign body reaction Humans Insulin Medicine Epithelial–mesenchymal transition Catheter obstructions 030304 developmental biology 0303 health sciences Type 1 diabetes business.industry Foreign-Body Reaction 021001 nanoscience & nanotechnology medicine.disease 3. Good health Catheter Diabetes Mellitus Type 1 medicine.anatomical_structure Insulin aggregation Biocompatibility Foreign body 0210 nano-technology business [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Journal of Controlled Release Journal of Controlled Release, Elsevier, 2021, 336, pp.1-15. ⟨10.1016/j.jconrel.2021.06.005⟩ |
| ISSN: | 0168-3659 |
| Popis: | International audience; Continuous intraperitoneal insulin infusion, from an implanted insulin pump connected to a catheter that delivers insulin directly to the peritoneal cavity has many clinical advantages for patients with Type 1 diabetes. However, the ongoing incidence of catheter obstructions remains a barrier to the widespread use of this therapy. To date, the root cause of these obstructions remains unknown. Here, a two-year clinical investigation was conducted, along with the development of an animal model to enable a mechanistic investigation into this issue. This novel animal model was able to mimic the catheter obstructions that occur in patients and, fortuitously, at an accelerated rate. This model allowed for independent assessment of each potential cause associated with catheter obstructions to help identify the root cause. Both macroscopic and microscopic analysis were conducted with regards to the onset and progression of catheter obstructions, along with monitoring of insulin delivery. Interestingly, although insulin aggregation occurs in insulin pumps and insulin aggregates were found in some catheter obstructions, insulin is unlikely to be the root cause, since obstructions also occurred in the control groups where only diluent (no insulin) was administered to the animals. Inflammatory cells, different phenotypes of fibroblasts, as well as collagen were observed in all obstructed catheters explanted from the patients and the animals. The presence of these cells and collagen is indicative of a typical foreign body reaction. In addition, the dynamic change in the fibroblasts with respect to morphology, phenotype, and spatial distribution suggests that tissue irritation-mediated epithelial to mesenchymal transition plays a role in catheter obstructions. |
| Databáze: | OpenAIRE |
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