Project description:BACKGROUND: Despite best supportive intensive care, the development of severe sepsis and septic shock after trauma is still associated with a high mortality rate in intensive care units (ICU). Incomplete knowledge of the pathophysiological and biochemical mechanisms that lead to perturbations of the host system is a major cause for this clinical entity. This lack of knowledge is mirrored in a delay in both diagnosis of sepsis and stratification of patients at risk. The current diagnostic and classification methods do not provide an early and reliable evidence for the development of sepsis and consequently lead to uncertainty in the classification and a delay in the initiation of an adequate therapy. Here, we present a prospective study performed with a well-defined patient cohort suffering from severe multiple trauma (n=85), in which we aimed to uncover the biological reasons why patients with multiple trauma can have dramatically different outcomes after suffering similar traumatic insults. METHODS: We used peripheral whole blood obtained with the PaxGene system at the time of admission to the ICU, i.e., 12 hours after trauma, for transcriptome analysis and monitored clinically the sequence of events from the admission to the ICU, to the very onset of sepsis and finally to the full development of multiple organ dysfunction syndrome (MODS). Study protocols and standard operating procedures (SOPs) regarding ethics, patient recruitment, logistics in sample acquisition and storage, microarray experiments, data analysis and data management have been developed and provided for a high feasibility and reproducibility of the investigations. FINDINGS: The transcriptome analysis from peripheral blood revealed a strong host response upon severe injury and demonstrated the suitability of whole blood in the PaxGene system as a surrogate marker in clinical gene expression studies. It was evident that patients who developed sepsis in the course of the disease (3-5 days after admission) showed an imbalance in the TH1/TH2 response towards a pronounced TH2 response, soon after trauma. The imbalanced TH1/TH2 shift along with inactivation of T cells, neutrophils, monocytes and macrophages might be critical factors for the initiation of a septic program seen in these patients 12 hours after trauma. INTERPRETATION: First, in this study, we provide protocols for logistics and infrastructure that can be applied generally to successfully integrate gene expression analysis studies in a clinical routine and demonstrate that by following these protocols, dedicated and reproducible results can be obtained. Second, we showed that peripheral whole blood is a suitable surrogate marker for the host response as it contains lots of “information” and is easily accessible. Third, we identified mechanisms involved in the perturbations of the immune system that lead to sepsis. Keywords: Prospective study

Project description:BACKGROUND: Despite best supportive intensive care, the development of severe sepsis and septic shock after trauma is still associated with a high mortality rate in intensive care units (ICU). Incomplete knowledge of the pathophysiological and biochemical mechanisms that lead to perturbations of the host system is a major cause for this clinical entity. This lack of knowledge is mirrored in a delay in both diagnosis of sepsis and stratification of patients at risk. The current diagnostic and classification methods do not provide an early and reliable evidence for the development of sepsis and consequently lead to uncertainty in the classification and a delay in the initiation of an adequate therapy. Here, we present a prospective study performed with a well-defined patient cohort suffering from severe multiple trauma (n=85), in which we aimed to uncover the biological reasons why patients with multiple trauma can have dramatically different outcomes after suffering similar traumatic insults. METHODS: We used peripheral whole blood obtained with the PaxGene system at the time of admission to the ICU, i.e., 12 hours after trauma, for transcriptome analysis and monitored clinically the sequence of events from the admission to the ICU, to the very onset of sepsis and finally to the full development of multiple organ dysfunction syndrome (MODS). Study protocols and standard operating procedures (SOPs) regarding ethics, patient recruitment, logistics in sample acquisition and storage, microarray experiments, data analysis and data management have been developed and provided for a high feasibility and reproducibility of the investigations. FINDINGS: The transcriptome analysis from peripheral blood revealed a strong host response upon severe injury and demonstrated the suitability of whole blood in the PaxGene system as a surrogate marker in clinical gene expression studies. It was evident that patients who developed sepsis in the course of the disease (3-5 days after admission) showed an imbalance in the TH1/TH2 response towards a pronounced TH2 response, soon after trauma. The imbalanced TH1/TH2 shift along with inactivation of T cells, neutrophils, monocytes and macrophages might be critical factors for the initiation of a septic program seen in these patients 12 hours after trauma. INTERPRETATION: First, in this study, we provide protocols for logistics and infrastructure that can be applied generally to successfully integrate gene expression analysis studies in a clinical routine and demonstrate that by following these protocols, dedicated and reproducible results can be obtained. Second, we showed that peripheral whole blood is a suitable surrogate marker for the host response as it contains lots of “information” and is easily accessible. Third, we identified mechanisms involved in the perturbations of the immune system that lead to sepsis. Keywords: Prospective study 159 consecutive traumatized patients were included in the study upon admission to the intensive care unit (ICU), fulfilling all of the following inclusion criteria: severe injuries to at least two body regions or three major fractures, between 18 and 65 years of age, an estimated Injury Severity Score (ISS) of ?15 points after thorough assessment of injuries, <12 hours between the occurrence of the accident and the time of admission to the ICU, and at least greater than 3 days of survival. None of the patients underwent neuro- or cardiac surgery. We excluded patients with severe intracranial head injuries, coagulation abnormalities known at the day of admission to the ICU, acute renal failure, liver failure, malignant disease, or hemofiltration in the patient`s history. The Patients were divided into two groups depending on their posttraumatic course: Patients not complicatd by sepsis (Group: N) and Patients complicated by sepsis (Group: S). Using the CodeLink UniSet Human 10 K Bioarrays (GE Healthcare, Freiburg, Germany), we searched for early differences in the transcriptome of these two groups. Only whole blood samples drawn upon admission to the ICU were used for this investigation. Microarray results were validated by quantification of mRNA by TaqMan® technology. Each patient sample was hybridized in duplicate or triplicate on microarrays (label-extract technical replicate). A total of 72 arrays (36 group N, 36 group S) were subjected to microarray quality analysis. Of these, 2 arrays (0 group N, 2 group S) were excluded from the data set due to quality reasons and a final set of 70 arrays (36 group N and 34 group S) were subjected to microarray analysis. Since the eliminated 2 arrays belonged to patients with three replicates, they were treated as two replicates in the further analysis. The arrays were designated N_xx_yy_z or S_xx_yy_z, with x for the patient-ID (1,2,3,4..) and z for the technical replicate number (1,2 or 3).

Project description:ObjectivePolytrauma is a complex condition associated with poor outcomes and high mortality rates resulting from severe damage and complicated complications. This study sought to ascertain the incidence of chronic complications in polytrauma patients, as well as the early immune changes and risk factors.MethodsA multicenter, prospective and observational cohort study was conducted at the emergency surgery or traumatic intensive care unit (TICU) of the Advanced Trauma Center from August 2020 to July 2023. A total of 2033 consecutive trauma patients were included in the study. In the first 1, 7, and 14 days after admission, flow cytometry and immunoassay kits were used to examine cytokine release and lymphocyte count.ResultsTrauma patients were reported 33.8% (687/2033) chronic complication rates, with monotrauma patients reported 8.1% (55/683) and polytrauma patients reported 59.4% (802/1350). And the four most frequent chronic complications in polytrauma patients were chronic musculoskeletal pain (30.4%), post-traumatic osteoarthritis (27.2%), chronic wound (21.6%), and chronic lung injury (14.1.%) .There were significant differences in lymphocyte ratios and cytokine levels, at 1, 7, and 14 day of admission between chronic complication groups (CCP) and not chronic complication groups (N-CCP) in polytrauma. Polytrauma patients with characteristics of higher ratio of Ts7d ratio (95% CI: 2.01-6.21), Treg14d (95% CI: 1.12-5.43) and level of IL-67d (95% CI: 1.22-4.43), TNF-α7d (95% CI: 1.05-3.83), IL-1014d (95% CI: 2.01-6.84) were found to have a higher likelihood of experiencing a chronic complication. Conversely, a higher ratio of Tc1d (95% CI: 0.53-0.86), Th1d (95% CI: 0.64-0.95) and Th/Ts14d (95% CI: 0.21-0.64) were identified as independent protective factors against a chronic complication event.ConclusionPolytrauma patients exhibit a notable prevalence of chronic complications. Some immune and inflammatory indicators can be observed early in combination after injury to predict the risk of chronic complications after polytrauma.

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What can we learn about polytrauma typologies by comparing population-representative to trauma-exposed samples: A Nepali example.

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What can we learn about polytrauma typologies by comparing population-representative to trauma-exposed samples: A Nepali example.

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