Chronic clinical illness (review)

The phenotype «chronic critical illness» includes various endotypes: critical illness polyneuromyopathy, acquired weakness syndrome in the intensive care unit, persistent inflammation, immunosuppression and catabolism syndrome (definition of the UF SCIRS Sepsis and Critical Illness Research Center of the University of Florida [Fr. Moree et al, 2012].

Considering the increasing prevalence of PICS in patients with chronic critical illness (as well as the number of rehospitalizations, disability and mortality), there is an urgent need for scientific research on such conditions.

The aim of the work: to analyze the data of literature reviews concerning new aspects of knowledge about chronic critical illness, to a greater extent, the syndrome of consequences of intensive care (PICS-CCI).

1. Ohl, K ., Tenbrock, K. Reactive oxygen species as regulators of MDSC-mediated immune suppression / K. Ohl, K. Tenbroch // Frontiers in Immunology. 2018. № 9. Mode of access: https://doi.org/10.3389/fimmu.2018.02499. Date of access: 10.04.2025.

2. Huet, O. Oxidative stress and endothelial dysfunction during sepsis / O. Huet [et al.] // Frontiers in Bioscience. 2011. № 16. P. 1986–1995.

3. Chan, E. L ., Murphy, J. T. Reactive oxygen species mediate endotoxin-induced human dermal endothelial NF-kappaB activation / E. L. Chan, J. T. Murphy // Journalof Surgical Research. 2003. № 111. P. 120–126.

4. Klawitter, F. Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review / F. Klawitter [et al.] // International Journal of Molecular Sciences. 2023. № 24. Mode of access: https://doi.org/10.3390/ijms24065516. Date of access: 10.04.2025.

5. Puthucheary, Z. A. Acute skeletal muscle wasting in critical illness / Z. A. Puthucheary [et al.] // JAMA. 2013. № 310. P. 1591–1600.

6. Yao, X. Mitochondrial ROS induces cardiac inflammation via a pathway through mtDNA damage in a pneumonia-related sepsis model / X. Yao [et al.] // PLoS ONE. 2015. № 10. Mode of access: https://doi.org/10.1371/journal.pone.0139416. Data of access: 10.04.2025.

7. Gong, Y. Importance of Toll-like receptor 2 in mitochondrial dysfunction during polymicrobial sepsis / Y. Gong [et al.] // Anesthesiology. 2014. № 121. P. 1236–1247.

8. Callahan, L. A .,Supinski, G. S. Sepsis-induced myopathy / L. A. Callahan, G. S. Supinski // Critical Care Medicine. 2009. № 37. P. 354–367.

9. Pannerec, A. Defining skeletal muscle resident progenitors and their cell fate potentials / A. Pannerec [et al.] // Development. 2013. № 140. P. 2879–2891.

10. Yin, H. , Price, F., Rudnicki, M. A. Satellite Cells and the Muscle Stem Cell Niche / H. Yin, F. Price, M. A. Rudnicki // Physiological Reviews. 2013. № 93. P. 23–67.

11. Abreu, P ., Kowaltowski, A. J. Satellite cell self-renewal in endurance exercise is mediated by inhibition of mitochondrial oxygen consumption / P. Abreu, A. J. Kowaltowski // Journal of Cachexia, Sarcopenia and Muscle. 2020. № 11. P. 1661–1676.

12. Stortz, J. A . Evidence for persistent immune suppression in patients who develop chronic critical illness after sepsis / J. A. Stortz [et al.] // Shock. 2018. № 49. –P. 249–258.

13. Jensen, I. J. Sepsis-induced T cell immunoparalysis: The ins and outs of impaired T cell immunity / L. J. Jensen [et al.] // Journal of Immunology. 2018. № 200. P. 1543–1553.

14. Hotchkiss, R. S. Monneret, G., Payen, D. Sepsis-induced immunosuppression: From cellular dysfunctions to immunotherapy / R. S. Hotchkiss, G. Monneret, D. Payen // Nature Reviews Immunology. 2013. № 13. P. 862–874.

15. Loss, S. H. Chronic critical illness: Are we saving patients or creating victims? / S. H. Loss [et al.] // RevistaBrasileria de TerapiaIntensiva. 2017. № 29. P. 87–95.

16. Gardner, A. K. The development of chronic critical illness determines physical function, quality of life, and long-term survival among early survivors of sepsis in surgical ICUs / A. K. Gardner [et al.] // Critical Care Medicine. 2019. № 47. P. 566–573.

17. Faroogh, M . MSCs and their exosomes: a rapidly evolving approach in the context of cutaneous wounds therapy / M. Faroogh [et al.] // Stem Cell Research & Therapy. 2021. № 12. Mode of access: https://doi.org/10.1186/s13287-02102662-6. Date of access: 10.04.2025.

18. Lotfy, A ., AboQuella, N. M., Wang, H. Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials / A. Lotfy, N. M. AboQuella, H. Wang // Stem Cell Research & Therapy. 2023. № 14. Mode of access: https://doi.org/10.1186/s13287023-03287-7. Date of access: 10.04.2025.

19. Harrell, C. R. Therapeutic Use of Mesenchymal Stem Cell-Derived Exosomes: From Basic Science to Clinics / C. R. Harrell [et al.] // Pharmaceutics. 2020. № 12. Mode of access: https://doi.org/10.3390/pharmaceutics12050474. Data of access: 10.04.2025.

20. Fu, Y. Trophic Effects of Mesenchymal Stem Cells in Tissue Regeneration / Y. Fu [et al.] // Tissue Engineering Part B: Reviews. 2017. № 23. P. 515–528.

21. Harrell, C. R . Molecular Mechanisms Respon-ible for Anti-inflammatory and Immunosuppressive Effects of Mesenchymal Stem Cell-Derived Factors / C. R. Harrell [et al.] // Advances in Experimental Medicine and Biology. 2019. № 1084. P. 187–206.

22. Huang, D . Role of mesenchymal stem cellderived exosomes in the regeneration of different tissues / H. Defa [et al.] // Journal of Biological Engineering. 2024. № 18. Mode of access: https://doi.org/10.1186/s13036-024-00431-6. Data of access: 10.04.2025.

23. Hade, M. D ., Suire, C. N., Suo, Z. Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine / M. D. Hade, C. N. Suire, Z. Suo // Cells. 2021. № 10. Mode of access: https://doi.org/10.3390/cells10081959. Data of access: 10.04.2025.

24. Jahangiri, B . Dual impacts of mesenchymal stem cell-derived exosomes on cancer cells: unravelling complex interactions / B. Jahangiri // Journal of Cell Communication and Signaling. 2023. № 17. P. 1229–1247.

25. Toh, W. S. MSC exosome as a cell-free MSC therapy for cartilage regeneration: implications for osteoarthritis treatment / W. S. Toh [et al.] // Seminars in Cell and Developmental Biology. 2017. № 67. P. 56–64.

26. Heldring, N. Therapeutic potential of multipotent mesenchymal stromal cells and their extracellular vesicles / N. Heldring [et al.] // Human Gene Therapy. 2015. Vol. 26, № 8. P. 506–517.

27. Wang, C. Mesenchymal stromal cell exosomes for drug delivery of prostate cancer treatments: a review / C. Wang [et al.] // Stem Cell Research & Therapy. 2025. № 16. Mode of access: https://doi.org/10.1186/s13287-025-04133-8. Data of access: 10.04.2025.

28. Xun, C. Insight into the proteomic profiling of exosomes secreted by human OM-MSCs reveals a new potential therapy / C. Xun [et al] // Biomedicine & Pharmacotherapy. 2020. № 131. Mode of access: https://doi.org/10.1016/j.biopha.2020.110584. Data of access: 10.04.2025.

29. Hassanzadeh A. Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities / A. Hassanzadeh [et al.] //Stem Cell Research & Therapy. 2021. № 12. Mode of access: https://doi.org/10.1186/s13287-02102378-7. Data of access: 10.04.2025.

30. Deng, H. Lipid, Protein, and MicroRNA Composition Within Mesenchymal Stem Cell-Derived Exosomes / H. Deng [et al.] // Cell Reprogram. 2018. № 20. P. 178–186.

31. Qiu, G. Mesenchymal stem cell-derived extracellular vesicles affect disease outcomes via transfer of microRNAs / G. Qiu [et al.] // Stem Cell Research & Therapy. 2018. –№ 9. Mode of access: https://doi.org/10.1186/s13287-0181069-9. Data of access: 10.04.2025.

32. Harrell, C. R. Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases / C. R. Harrell [et al.] // Cells. 2019. № 8. Mode of access: https://doi.org/10.3390/cells8121605. Data of access: 10.04.2025.

33. Mendt, M ., Rezvani, K., Shpall, E. Mesenchymal stem cell-derived exosomes for clinical use / M. Mendt, K. Rezvani, E. Shpall // Bone Marrow Transplantation. 2019. № 54. P. 789–792.