Time Window-Based Platform for the Rapid Stratification of Blunt Trauma Patients into Distinct Outcome Cohorts

Abstract

Provided herein are methods for segregating trauma, e.g., blunt trauma, patients into different cohorts based on risk of multiple organ dysfunction syndrome using patient data obtained within a short time window following injury. The methods are useful in providing treatment to trauma patients, and for separating trauma patients into cohorts.

What is claimed is: 
     
         1 . A method of managing a trauma injury patient or a method of determining risk of multiple organ dysfunction in a patient, comprising:
 obtaining within a window of time after injury a patient's values for members of a panel of biomarkers, clinical variables, and/or genetic polymorphisms that are, as a group, able to segregate, using one or more statistical and/or mathematical methods on a data set of a statistically-significant size, patients at least into group of patients that experience high risk, and patients that experience low risk, of multiple organ dysfunction with clinically-acceptable specificity and selectivity;   determining, using a computer-implemented method, a value for the obtained patient's values for each member of the panel of biomarkers, clinical variables, and/or genetic polymorphisms against a set of stored values for a statistically-significant number of patients, and calculating a representation of those values to produce a panel value;   determining, using a computer-implemented method, if the panel value for the patient is within a range of panel values for the set of stored values within which patients experience a clinically-relevant risk of multiple organ dysfunction or nosocomial infection; and   producing, using a computer-implemented method, an output indicating whether the patient is expected to experience a risk of multiple organ dysfunction or nosocomial infection.   
     
     
         2 . The method of  claim 1 , wherein the range of panel values is a range or cluster of values representing a different predicted patient outcome as compared to a different range or cluster of values. 
     
     
         3 . The method of  claim 1 , comprising:
 obtaining a patient's values for members of a panel of biomarkers, clinical variables, and/or genetic polymorphisms that are, as a group, able to segregate, using a statistical ranking method on a data set of a statistically-significant size, patients into a group of patients that experience multiple organ dysfunction with clinically-acceptable specificity and selectivity;   determining, using a computer-implemented method, a rank value for the obtained patient's values for each member of the panel of biomarkers, clinical variables, and/or genetic polymorphisms against a set of stored values for a statistically-significant number of patients, and calculating a representation of those rank values of those rank values to produce a panel rank value;   determining, using a computer-implemented method, if the panel rank value for the patient is above or below a panel rank value threshold for the set of stored values above which patients experience a clinically-relevant risk of multiple organ dysfunction or nosocomial infection; and   producing, using a computer-implemented method, an output indicating whether the patient is expected to experience a clinically-relevant, significant risk of multiple organ dysfunction or nosocomial infection.   
     
     
         4 . The method of  claim 3 , wherein the panel rank value is a rank sum value for members, such as all members of the panel other than those generating binary values. 
     
     
         5 . The method of  claim 4 , wherein the panel rank threshold is a panel rank sum value above which patients experience a clinically-relevant risk of multiple organ dysfunction or nosocomial infection that is at least 55% of the maximum panel rank sum value for the stored values. 
     
     
         6 . The method of  claim 4 , wherein the panel rank threshold is a panel rank sum value above which patients experience a clinically-relevant risk of multiple organ dysfunction or nosocomial infection that is 61% of the maximum panel rank sum value for the stored values. 
     
     
         7 . The method of  claim 1 , wherein the patient's values for members of a panel of biomarkers and clinical variables are obtained within a window of time of from immediately after injury to one month after injury, such as within 24 hours of injury. 
     
     
         8 . The method of  claim 1 , wherein the patient is admitted to an intensive care unit and has a likelihood of survival of at least 24 hours. 
     
     
         9 . The method of  claim 1 , wherein the trauma is blunt trauma, such as non-penetrating blunt trauma. 
     
     
         10 . The method of  claim 1 , wherein the statistical and/or mathematical method segregates patients into a group of patients that experience multiple organ dysfunction an average multiple organ dysfunction score as measured on days 2-5 after injury, such as an average Marshall's multiple organ dysfunction score as measured on days 2, 3, 4, and 5 after injury (aMOD D2-D5 ), where a score of less than or equal to three is indicative of no multiple organ dysfunction, and a score of greater than three is indicative of multiple organ dysfunction. 
     
     
         11 . The method of  claim 1 , further comprising adding the patient's values and the patient's outcome, including aMOD D2-D5 , or an equivalent thereof, survival, and/or presence of nosocomial infection, to the set of stored values. 
     
     
         12 . The method of  claim 1 , wherein the stored data set comprises at least 100 values from different patients for each member of the panel of biomarkers, clinical variables, and/or genetic polymorphisms. 
     
     
         13 . The method of  claim 1 , wherein the panel of biomarkers, clinical variables, and/or genetic polymorphisms includes one or more polymorphism selected from:
 homozygous (AA) for a cytosine (C) at rs10741668, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R 2 >0.75;   homozygous for a guanine (G) at rs10790334, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R 2 >0.75;   homozygous for a C at rs2065418, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R 2 >0.75;   heterozygous (AB) for a G at rs2241777, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R 2 >0.75;   heterozygous for a thymine (T) at rs3134287, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R 2 >0.75;   heterozygous for an adenine (A) at rs3098223, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R 2 >0.75; and   heterozygous for a T at rs906790, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R 2 >0.75.   
     
     
         14 . The method of  claim 1 , wherein the panel of biomarkers, clinical variables, and/or genetic polymorphisms comprise: interleukin 10 (IL-10), MCP-1/CCL2, Cl, CO 2 , creatinine, partial thromboplastin time (PTT), and platelet counts, or the panel of biomarkers, clinical variables, and/or genetic polymorphisms consists of: interleukin 10 (IL-10), MCP-1/CCL2, Cl, CO2, creatinine, partial thromboplastin time (PTT), and platelet counts. 
     
     
         15 . The method of  claim 1 , wherein the panel of biomarkers, clinical variables, and/or genetic polymorphisms comprise one or more, or all of: IL-6, MCP-1, IL-10, IL-8, IP-10, sST2, and MIG. 
     
     
         16 . The method of  claim 1 , wherein the panel rank threshold above which patients experience a clinically-relevant risk of multiple organ dysfunction or nosocomial infection is at least 55% of the maximum panel rank. 
     
     
         17 . The method of  claim 1 , further comprising performing the method on one or more additional patients and categorizing the patients in at least two groups, including: a first group of patients is expected not to experience a significant risk of multiple organ dysfunction or nosocomial infection, and a second group of patients expected to experience a significant risk of multiple organ dysfunction or nosocomial infection. 
     
     
         18 . The method of  claim 17 , further comprising treating the patients with a compound or composition, such as an anti-inflammatory compound, that is being evaluated for safety and effectiveness in prevention or treatment of multiple organ dysfunction syndrome. 
     
     
         19 . The method of  claim 1 , further comprising when a patient is indicated in the output to be expected to experience a significant risk of multiple organ dysfunction or nosocomial infection, treating the patient with an effective amount of a therapeutic agent effective for treatment of multiple organ dysfunction syndrome, that is optionally an immune modulator or an anti-inflammatory therapeutic agent, such as a compound or composition for use in decreasing a Th17 inflammatory response, and/or an antibiotic. 
     
     
         20 . A system comprising a computer, instructions for performing the method of  claim 1 , and a computer-readable medium comprising the set of stored values for a statistically-significant number of patients for panel of patient biomarkers, clinical variables, and/or genetic polymorphisms.