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The Gut-Lymph Model Gives New Treatment Strategies for Organ Failure

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To identify the key insights or developments described in this article
1 Credit CME

Each year, more than 20 million people with organ failure (OF) are admitted to intensive care units around the world.1 With a 30% mortality rate, it remains the leading cause of death in intensive care units. OF is preceded by 2 syndromes, the systemic inflammatory response (SIRS) and multiple organ dysfunction (MODS), which can progress throughout days or weeks to single or multiple OF and death.2 This patterned sequence is the feared sequelae of many inciting acute and critical diseases (ACDs), which include severe sepsis, hemorrhage, trauma, burns, acute pancreatitis, and most recently, SARS-CoV-2 infection.3 The heart, lung, and kidney organ systems are most at risk of failing. The failure to translate multiple putative drug treatments to arrest OF is well documented.2 Current treatment standards for SIRS/MODS/OF are generic, including fluid resuscitation, inotropes, mechanical ventilation, and kidney replacement therapy. While optimizing physiology is a worthy goal,3 there is an urgent need for a new paradigm to introduce effective treatment strategies that go beyond organ support to target specific disease mechanisms to mitigate SIRS/MODS/OF and the risk of death.

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Article Information

Corresponding Author: John A. Windsor, MD, Surgical and Translational Research Centre, Faculty of Medical Health Sciences, University of Auckland, Park Road, Bldg 507, Room 2004, Grafton, Auckland 1142, New Zealand (j.windsor@auckland.ac.nz).

Published Online: April 20, 2022. doi:10.1001/jamasurg.2022.0654

Conflict of Interest Disclosures: Drs Windsor, Trevaskis, and Phillips reported a patent for PCT/AU2021/051242 issued for a lymph-directing formulation for a lipase inhibitor to prevent/treat organ failure. Dr Trevaskis reported a patent for PCT/AU2020/050997 licensed to PureTech Health for a lymph-directing prodrug technology. No other disclosures were reported.

References
1.
Adhikari  NK , Fowler  RA , Bhagwanjee  S , Rubenfeld  GD .  Critical care and the global burden of critical illness in adults.   Lancet. 2010;376(9749):1339-1346. doi:10.1016/S0140-6736(10)60446-1PubMedGoogle ScholarCrossref
2.
Lelubre  C , Vincent  J-L .  Mechanisms and treatment of organ failure in sepsis.   Nat Rev Nephrol. 2018;14(7):417-427. doi:10.1038/s41581-018-0005-7PubMedGoogle ScholarCrossref
3.
Baker  T , Schell  CO , Petersen  DB ,  et al.  Essential care of critical illness must not be forgotten in the COVID-19 pandemic.   Lancet. 2020;395(10232):1253-1254. doi:10.1016/S0140-6736(20)30793-5PubMedGoogle ScholarCrossref
4.
Deitch  EA .  Gut lymph and lymphatics: a source of factors leading to organ injury and dysfunction.   Ann N Y Acad Sci. 2010;1207(suppl 1):E103-E111. doi:10.1111/j.1749-6632.2010.05713.xPubMedGoogle ScholarCrossref
5.
Windsor  JA , Escott  A , Brown  L , Phillips  AR .  Novel strategies for the treatment of acute pancreatitis based on the determinants of severity.   J Gastroenterol Hepatol. 2017;32(11):1796-1803. doi:10.1111/jgh.13784PubMedGoogle ScholarCrossref
6.
Oliver  G , Kipnis  J , Randolph  GJ , Harvey  NL .  The lymphatic vasculature in the 21st century: novel functional roles in homeostasis and disease.   Cell. 2020;182(2):270-296. doi:10.1016/j.cell.2020.06.039PubMedGoogle ScholarCrossref
7.
Trevaskis  NL , Kaminskas  LM , Porter  CJ .  From sewer to saviour: targeting the lymphatic system to promote drug exposure and activity.   Nat Rev Drug Discov. 2015;14(11):781-803. doi:10.1038/nrd4608PubMedGoogle ScholarCrossref
8.
Shanbhag  ST , Choong  B , Petrov  M , Delahunt  B , Windsor  JA , Phillips  ARJ .  Acute pancreatitis conditioned mesenteric lymph causes cardiac dysfunction in rats independent of hypotension.   Surgery. 2018;163(5):1097-1105. doi:10.1016/j.surg.2017.12.013PubMedGoogle ScholarCrossref
9.
Wang  HW , Escott  AB , Phang  KL , Petrov  MS , Phillips  AR , Windsor  JA .  Indications, techniques, and clinical outcomes of thoracic duct interventions in patients: a forgotten literature?   J Surg Res. 2016;204(1):213-227. doi:10.1016/j.jss.2016.04.050PubMedGoogle ScholarCrossref
10.
Itkin  M , Nadolski  GJ .  Modern techniques of lymphangiography and interventions: current status and future development.   Cardiovasc Intervent Radiol. 2018;41(3):366-376. doi:10.1007/s00270-017-1863-2PubMedGoogle ScholarCrossref
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