Invited Commentary
May 17, 2023
Long-Term Impact of Trauma in Twins
Timothy A. Pritts
JAMA Surg. 2023;158(7):746. doi:10.1001/jamasurg.2023.1568
Trauma remains a leading cause of death and disability worldwide. For those who survive a severe traumatic injury, the personal costs are subjectively substantial but may be difficult to objectively quantify. Previous studies attempting to do this have determined that many factors are associated with long-term outcomes, including injury severity,1 age,2 sex,3 presence of traumatic brain injury,4 insurance status,5 and household size.2
Additional studies have attempted to evaluate the long-term impact of trauma on physiological processes. Investigators have demonstrated alterations in the inflammatory and immune responses after trauma,6-8 but these studies have focused on relatively short-term time points. Although the long-term effects of traumatic injury on inflammatory and immune responses remain incompletely understood, studies in burn patients indicate that the effects of thermal injury on metabolism and inflammatory pathways likely persist for years, if not permanently.9
The study by Eskesen et al10 adds significantly to our understanding of the real long-term cost of traumatic injury. The investigators sought to address the question of whether moderate to severe trauma is associated with increased risk of late death, immune-mediated disease, or cancer. To investigate this, they used the Danish Twins Registry and the Danish National Patient Registry to identify twin pairs where 1 twin experienced a moderate or severe traumatic injury (defined as an Injury Severity Score ≥9) and the other did not. Their analysis included 2290 pairs of twins with a median follow-up time of 8.6 years.
The results of this study are striking. The hazard ratio for the twin who was exposed to trauma reaching the composite outcome of death or 1 of 24 predefined immune-mediated or cancer diseases was 1.33 when compared with the uninjured twin. When components of the composite outcome were analyzed separately, the data demonstrated that the twin exposed to moderate to severe injury had a relative hazard ratio of 1.91 for death and 1.28 for immune-mediated disease or cancer. Further analysis suggested that this association was more pronounced in male, compared with female, twins and was similar in monozygotic compared with dizygotic twin pairs.
This study is extremely informative. Due to the nature of the Danish registry system, the investigators were able to examine the outcomes for a relatively large study population in great detail. The use of same-sex twin pairings in a registry approach allowed the investigators to control for several factors, including age, sex, and environment. The finding that previous trauma resulted in increased immune-mediated diseases strongly suggests a long-term effect of injury on inflammatory pathways, similar to that seen in burn patients, but further detailed study is needed to increase our understanding of this effect. The findings of a lack of association of monozygotic compared with dizygotic twinning suggests that there are likely many factors in addition to purely genetic ones that are important to long-term outcomes. In addition, the investigators found that increasing Injury Severity Score was associated with decreased hazard ratios for reaching the composite outcome. This is highly counterintuitive and should be the subject of further investigation. Furthermore, the median follow-up period of 8.6 years allows substantial room for future study of this population to determine the lifetime effect of trauma on outcomes. Taken together, there is much to be learned—now and in the future—from tales of trauma in twins.
