# US 2018/0322956 A1 · Time Window-Based Platform for the Rapid Stratification of Blunt Trauma Patients into Distinct Outcome Cohorts

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- Number: US 2018/0322956 A1
- Document ID: US20180322956A1
- Status: Published application
- Kind: A1
- Application number: 15/971,519
- Filed: 2018-05-04
- Published: 2018-11-08
- Earliest claimed: 2017-05-05
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh - Of the Commonwealth System of Higher Education
- Inventors: Gregory M. Constantine; Timothy Billiar; Qi Mi; Yoram Vodovotz; Rami Namas; Lukas Schimunek
- Web page: https://patentgrep.com/patent/US20180322956A1

## CPC

- G16H 50/30: for calculating health indices; for individual health risk assessment
- G16B 20/20: Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
- G16B 40/00: ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
- G16B 40/30: Unsupervised data analysis
- G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients
- G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems
- G16H 50/70: for mining of medical data, e.g. analysing previous cases of other patients
- G16H 70/40: relating to drugs, e.g. their side effects or intended usage
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 3)

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.

### Claim 5 (depends on 4)

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.

### Claim 6 (depends on 4)

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.

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 1)

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.

### Claim 9 (depends on 1)

The method of claim 1, wherein the trauma is blunt trauma, such as non-penetrating blunt trauma.

### Claim 10 (depends on 1)

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 (aMODD2-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.

### Claim 11 (depends on 1)

The method of claim 1, further comprising adding the patient's values and the patient's outcome, including aMODD2-D5, or an equivalent thereof, survival, and/or presence of nosocomial infection, to the set of stored values.

### Claim 12 (depends on 1)

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.

### Claim 13 (depends on 1)

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 R2>0.75;
homozygous for a guanine (G) at rs10790334, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R2>0.75;
homozygous for a C at rs2065418, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R2>0.75;
heterozygous (AB) for a G at rs2241777, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R2>0.75;
heterozygous for a thymine (T) at rs3134287, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R2>0.75;
heterozygous for an adenine (A) at rs3098223, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R2>0.75; and
heterozygous for a T at rs906790, or a polymorphism in linkage disequilibrium therewith, such as where D′>0.75 or R2>0.75.

### Claim 14 (depends on 1)

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, CO2, 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.

### Claim 15 (depends on 1)

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.

### Claim 16 (depends on 1)

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.

### Claim 17 (depends on 1)

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.

### Claim 18 (depends on 17)

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.

### Claim 19 (depends on 1)

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.

### Claim 20 (depends on 1)

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.