From static to dynamic: a sepsis-specific dynamic model from clinical criteria in polytrauma patients

Namas, Rami A.; Vodovotz, Yoram

doi:10.21037/atm.2016.11.72

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…Sepsis is a dynamic process characterized by rapidly evolving physiological responses that may not be adequately captured by static measurements [ 14 , 33 ]. Compared to traditional static clustering methods, GBTM has the advantage of modeling the dynamic evolution of physiology over time.…”

Section: Discussionmentioning

confidence: 99%

“…Most studies have identified sub-phenotypes using static measurements of biomarkers or vital signs. However, sepsis is a dynamic process with biological and physiological responses that evolve over minutes to hours [ 12 – 14 ]. This “temporal instability” of sepsis suggests that static snapshots of labs and vitals may not identify sub-phenotypes that are consistent over time [ 15 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Development and validation of novel sepsis subphenotypes using trajectories of vital signs

et al. 2022

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Purpose Sepsis is a heterogeneous syndrome and identification of sub-phenotypes is essential. This study used trajectories of vital signs to develop and validate sub-phenotypes and investigated the interaction of sub-phenotypes with treatment using randomized controlled trial data. Methods All patients with suspected infection admitted to four academic hospitals in Emory Healthcare between 2014–2017 (training cohort) and 2018–2019 (validation cohort) were included. Group-based trajectory modeling was applied to vital signs from the first 8 h of hospitalization to develop and validate vitals trajectory sub-phenotypes. The associations between sub-phenotypes and outcomes were evaluated in patients with sepsis. The interaction between sub-phenotype and treatment with balanced crystalloids versus saline was tested in a secondary analysis of SMART (Isotonic Solutions and Major Adverse Renal Events Trial). Results There were 12,473 patients with suspected infection in training and 8256 patients in validation cohorts, and 4 vitals trajectory sub-phenotypes were found. Group A ( N = 3483, 28%) were hyperthermic, tachycardic, tachypneic, and hypotensive. Group B ( N = 1578, 13%) were hyperthermic, tachycardic, tachypneic (not as pronounced as Group A) and hypertensive. Groups C ( N = 4044, 32%) and D ( N = 3368, 27%) had lower temperatures, heart rates, and respiratory rates, with Group C normotensive and Group D hypotensive. In the 6,919 patients with sepsis, Groups A and B were younger while Groups C and D were older. Group A had the lowest prevalence of congestive heart failure, hypertension, diabetes mellitus, and chronic kidney disease, while Group B had the highest prevalence. Groups A and D had the highest vasopressor use ( p < 0.001 for all analyses above). In logistic regression, 30-day mortality was significantly higher in Groups A and D ( p < 0.001 and p = 0.03, respectively). In the SMART trial, sub-phenotype significantly modified treatment effect ( p = 0.03). Group D had significantly lower odds of mortality with balanced crystalloids compared to saline (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.23–0.67, p < 0.001). Conclusion Sepsis sub-phenotypes based on vital sign trajectory were consistent across cohorts, had distinct outcomes, and different responses to treatment with balanced crystalloids versus saline. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06890-z.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development and validation of novel sepsis subphenotypes using trajectories of vital signs

et al. 2022

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“…While most inflammatory mediators are pleiotropic in their functions, some can be defined as predominantly inflammatory, antiinflammatory, or reparative (11). Abrupt changes in the levels of circulating markers of immune and endothelial cell activation occur quickly after injury and correspond to quantitative and qualitative aspects of the human response to injury (10,(12)(13)(14)(15). For example, the dysregulation of immune responses leads to worsening short-term (<24 hours) and long-term (>30 days) outcomes related to infection (16), persistent illness (17), and mortality (18).…”

Section: Introductionmentioning

confidence: 99%

Prehospital plasma is associated with distinct biomarker expression following injury

Gruen¹,

Brown²,

Guyette³

et al. 2020

JCI Insight

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16 The PAMPer study group is detailed in Supplemental Acknowledgments. BACKGROUND. Prehospital plasma improves survival in severely injured patients transported by air ambulance. We hypothesized that prehospital plasma would be associated with a reduction in immune imbalance and endothelial damage. METHODS. We sampled blood from 405 trauma patients enrolled in the Prehospital Air Medical Plasma (PAMPer) trial upon hospital admission (0 hours) and 24 hours post admission across 6 U.S. sites. We assayed samples for 21 inflammatory mediators and 7 markers associated with endothelial function and damage. We performed hierarchical clustering analysis (HCA) of these biomarkers of the immune response and endothelial injury. Regression analysis was used to control for differences across study and to assess any association with prehospital plasma resuscitation. RESULTS. HCA distinguished two patient clusters with different injury patterns and outcomes. Patients in cluster A had greater injury severity and incidence of blunt trauma, traumatic brain injury, and mortality. Cluster A patients that received prehospital plasma showed improved 30day survival. Prehospital plasma did not improve survival in cluster B patients. In an adjusted analysis of the most seriously injured patients, prehospital plasma was associated with an increase in adiponectin, IL-1β, IL-17A, IL-23, and IL-17E upon admission, and a reduction in syndecan-1, TM, VEGF, IL-6, IP-10, MCP-1, and TNF-α, and an increase in IL-33, IL-21, IL-23, and IL-17E 24 hours later. CONCLUSION. Prehospital plasma may ameliorate immune dysfunction and the endotheliopathy of trauma. These effects of plasma may contribute to improved survival in injured patients. TRIAL REGISTRATION. NCT01818427.

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“…Numerical modeling has been applied to studies of the immune system and models may help to understand the relationships between various immune system components and the physiopathology of sepsis, thereby explaining phenomena that cannot be predicted intuitively [28,29]. Models could also help a physician to analyze a disease and make an optimal decision regarding the patient's treatment [29]. Furthermore, models can be used to simulate and test new therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling of septic shock: an innovative tool for assessing therapeutic hypotheses

et al. 2019

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Septic shock is provoked by hyper-activation of the pro-inflammatory response after infection and the patient requires anti-inflammatory treatment. However, the immune system develops a compensatory mechanism where the resulting feedback leads to an anti-inflammatory response after the initial state, which is referred to as immunodeficiency. Therefore, the initial therapeutic treatment with anti-inflammatory intervention has failed for almost 20 years and it has been changed in the last 10 years based on modulation of the inflammatory response. Using in silico methods, it is possible to develop a new approach based on physiopathology for treating septic shock. According to our new mathematical model, we can consider the dysfunctional immune system in a patient with septic shock and modify two parameters at different times to determine a possible treatment, and bearing out the single nucleoid polymorphism (SNP) may predominate the further deterioration of sepsis. The result represents the initial anti-inflammatory treatment with interleukin-10 activation and an increased risk of mortality over time for the septic shock patient, excluding the early stages. However, a hypothetical treatment based on interleukin-10 inhibition can change the patient's immune stage and provide a new therapy according to our results, and show that the frequency of pro-inflammatory related gene SNP can be the possibility of increase sepsis risk. In conclusion, our proposed in silico method can explore therapeutic strategies and predict their associated efficacy and important factors, with the ultimate objective of improving treatments to reduce mortality.

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From static to dynamic: a sepsis-specific dynamic model from clinical criteria in polytrauma patients

Cited by 7 publications

References 25 publications

Development and validation of novel sepsis subphenotypes using trajectories of vital signs

Development and validation of novel sepsis subphenotypes using trajectories of vital signs

Prehospital plasma is associated with distinct biomarker expression following injury

Mathematical modeling of septic shock: an innovative tool for assessing therapeutic hypotheses

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