Computational modelling of the inflammatory response in trauma, sepsis and wound healing: implications for modelling resilience

Resilience refers to the ability to recover from illness or adversity. At the cell, tissue, organ and whole-organism levels, the response to perturbations such as infections and injury involves the acute inflammatory response, which in turn is connected to and controlled by changes in physiology across all organ systems. When coordinated properly, inflammation can lead to the clearance of infection and healing of damaged tissues. However, when either overly or insufficiently robust, inflammation can drive further cell stress, tissue damage, organ dysfunction and death through a feed-forward process of inflammation → damage → inflammation. To address this complexity, we have obtained extensive datasets regarding the dynamics of inflammation in cells, animals and patients, and created data-driven and mechanistic computational simulations of inflammation and its recursive effects on tissue, organ and whole-organism (patho)physiology. Through this approach, we have discerned key regulatory mechanisms, recapitulated in silico key features of clinical trials for acute inflammation and captured diverse, patient-specific outcomes. These insights may allow for the determination of individual-specific tolerances to illness and adversity, thereby defining the role of inflammation in resilience.

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Role of Complement in Multiorgan Failure

Clinical and Developmental Immunology ◽

10.1155/2012/962927 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 44

Author(s):

Daniel Rittirsch ◽

Heinz Redl ◽

Markus Huber-Lang

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Inflammatory Response ◽

Complement System ◽

Multiorgan Failure ◽

Severe Trauma ◽

Organ Systems ◽

Activation Products ◽

The Complement System

Multiorgan failure (MOF) represents the leading cause of death in patients with sepsis and systemic inflammatory response syndrome (SIRS) following severe trauma. The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed.

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Biliary Drainage Before and After Liver Resection for Perihilar Cholangiocarcinoma

The American Surgeon ◽

10.1177/0003134820923287 ◽

2020 ◽

Vol 86 (6) ◽

pp. 628-634

Author(s):

Laura M. Enomoto ◽

Matthew E. B. Dixon ◽

Allene Burdette ◽

Niraj J. Gusani

Keyword(s):

Biliary Drainage ◽

Future Liver Remnant ◽

Preoperative Biliary Drainage ◽

Perihilar Cholangiocarcinoma ◽

Patient Specific ◽

Liver Remnant ◽

Biliary Sepsis ◽

Before And After

Perihilar cholangiocarcinoma (PHC) is a rare tumor that requires surgical resection for a potential cure. The role of preoperative biliary drainage has long been debated, given its treatment of biliary sepsis and decompression of the future liver remnant (FLR), but high procedure-specific morbidity. The indications, methods, and outcomes for preoperative biliary drainage are discussed to serve as a guide for perioperative management of patients with resectable PHC. Multiple studies from the literature related to perihilar cholangiocarcinoma, biliary drainage, and management of the FLR were reviewed. Commonly employed preoperative biliary drainage includes endoscopic biliary stenting and percutaneous transhepatic biliary drainage. Drainage of the FLR remains controversial, with most experts recommending drainage of the only in patients with an FLR <50%. Biliary drainage for resectable PHC requires a patient-specific approach with careful determination of the FLR and balancing of potential morbidity with the benefits of drainage.

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Resolution in an ‘over-inflamed’ era

The Biochemist ◽

10.1042/bio03904004 ◽

2017 ◽

Vol 39 (4) ◽

pp. 4-7

Author(s):

Mauro Perretti ◽

Trinidad MonteroMelendez

Keyword(s):

Inflammatory Response ◽

Acute Inflammation ◽

Pharmacological Intervention ◽

Acute Inflammatory Response ◽

Moderate Pain ◽

Antiinflammatory Drugs ◽

Protective Mechanisms ◽

Life Saving ◽

Common Perception

Unlike other pathologies, inflammation is a condition that all individuals experience in their lives. Toothache, sunburn, a twisted ankle or cutting your hand while slicing bread, they all evoke what we call an acute inflammatory response. This type of response normally displays the cardinal signs of inflammation originally described by Aulus Cornelius Celsus: redness, swelling, heat and pain. Acute inflammation does not normally require any therapeutic intervention other than perhaps a painkiller, as it resolves, with the damage being naturally repaired. Inflammation is also at the root of many other diseases in a more ‘silent’ way as the cardinal signs of inflammation are not so evident. It is now appreciated that inflammatory mechanisms and processes contribute to the pathogenesis of a number of conditions including obesity, cancer, rheumatoid arthritis, atherosclerosis and diabetes. These are examples of chronic inflammation, arising either by the persistence of the injurious element causing it, or by a defect in our endogenous natural protective mechanisms grouped under the terminology of pro-resolving mechanisms. A common perception, likely to have been enhanced by the large variety of nonprescription antiinflammatory drugs available to anyone experiencing mild-to-moderate pain, is that inflammation is something harmful that must be stopped. In the next sections we will discuss on the protective life-saving role of the inflammatory response, the existence of our own body's resolutive mechanisms that regulate it and on when and why we need a pharmacological intervention to treat inflammation.

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Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARγ receptors

International Immunopharmacology ◽

10.1016/j.intimp.2016.06.027 ◽

2016 ◽

Vol 38 ◽

pp. 434-442 ◽

Cited By ~ 5

Author(s):

Gholamreza Houshmand ◽

Mohammad Taghi Mansouri ◽

Bahareh Naghizadeh ◽

Ali Asghar Hemmati ◽

Mahmoud Hashemitabar

Keyword(s):

Inflammatory Response ◽

Acute Inflammation ◽

Anti Inflammatory

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Data-driven segregation of trauma patients using principal component analysis yields novel, patient-specific insights into acute inflammation

Journal of Critical Care ◽

10.1016/j.jcrc.2010.12.020 ◽

2011 ◽

Vol 26 (2) ◽

pp. e2

Author(s):

Ali Ghuma ◽

Cordelia Giraldo ◽

Rajaie Namas ◽

Juan Ochoa ◽

Timothy Billiar ◽

...

Keyword(s):

Principal Component Analysis ◽

Acute Inflammation ◽

Principal Component ◽

Component Analysis ◽

Data Driven ◽

Patient Specific ◽

Trauma Patients

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Potentiation of diclofenac-induced anti-inflammatory response by aminoguanidine in carrageenan-induced acute inflammation in rats: The role of nitric oxide

Inflammation Research ◽

10.1007/s00011-003-1189-1 ◽

2003 ◽

Vol 52 (9) ◽

pp. 378-382 ◽

Cited By ~ 18

Author(s):

A. A. Al-Majed ◽

M. Khattab ◽

M. Raza ◽

O. A. Al-Shabanah ◽

A. M. Mostafa

Keyword(s):

Nitric Oxide ◽

Inflammatory Response ◽

Acute Inflammation ◽

Anti Inflammatory

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On Future Directions in Pathology

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053991 ◽

1982 ◽

Vol 40 ◽

pp. 274-277

Author(s):

Benjamin F. Trump ◽

Irene K. Berezesky ◽

Raymond T. Jones

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Clinical Pathology ◽

Future Directions ◽

Diagnostic Pathology ◽

The Past ◽

Transmission Electron ◽

Organ Systems ◽

The Many

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.

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