In response to various immune challenges, females show better survival than males; the X chromosome has an important role in this immunological advantage. X chromosome-linked diseases are usually restricted to males, who have only one copy of the X chromosome; however, females are more prone to autoimmune diseases, and the X chromosome may be involved in the breakdown of self tolerance. Several hypotheses have been proposed in recent years that support a role for the X chromosome in shaping autoimmune responses. Here, we review the main mechanisms responsible for increased immune activity in females. This provides a survival advantage in the face of pathogenic insult but can also enhance the susceptibility of females to autoimmunity.

The X chromosome in immune functions: when a chromosome makes the difference

Do men die young and sick, or do women live long and healthy? By trying to explain the sexual dimorphism in life expectancy, both biological and environmental aspects are presently being addressed. Besides age-related changes, both the immune and the endocrine system exhibit significant sex-specific differences. This review deals with the aging immune system and its interplay with sex steroid hormones. Together, they impact on the etiopathology of many infectious diseases, which are still the major causes of morbidity and mortality in people at old age. Among men, susceptibilities toward many infectious diseases and the corresponding mortality rates are higher. Responses to various types of vaccination are often higher among women thereby also mounting stronger humoral responses. Women appear immune-privileged. The major sex steroid hormones exhibit opposing effects on cells of both the adaptive and the innate immune system: estradiol being mainly enhancing, testosterone by and large suppressive. However, levels of sex hormones change with age. At menopause transition, dropping estradiol potentially enhances immunosenescence effects posing postmenopausal women at additional, yet specific risks. Conclusively during aging, interventions, which distinctively consider the changing level of individual hormones, shall provide potent options in maintaining optimal immune functions.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.12326

How sex and age affect immune responses, susceptibility to infections, and response to vaccination

Trauma is still one of the main reasons for death among the population worldwide. Mortality occurring early after injury is due to "first hits", including severe organ injury, hypoxia, hypovolaemia or head trauma. Massive injury leads to activation of the immune system and the early inflammatory immune response after trauma has been defined as systemic inflammatory response syndrome (SIRS). "Second hits" such as infections, ischaemia/reperfusion or operations can further augment the pro-inflammatory immune response and have been correlated with the high morbidity and mortality in the latter times after trauma. SIRS can lead to tissue destruction in organs not originally affected by the initial trauma with subsequent development of multi-organ dysfunction (MOD). The initial pro-inflammatory response is followed by an anti-inflammatory response and can result in immune suppression with high risk of infection and sepsis. Trauma causes activation of nearly all components of the immune system. It activates the neuroendocrine system and local tissue destruction and accumulation of toxic byproducts of metabolic respiration leads to release of mediators. Extensive tissue injury may result in spillover of these mediators into the peripheral bloodstream to further maintain and augment the pro-inflammatory response. Hormones like ACTH, corticosteroids and catecholamines as well as cytokines, chemokines and alarmins play important roles in the initiation and persistence of the pro-inflammatory response after severe injury. The purpose of this review is therefore to describe the immunological events after trauma and to introduce important mediators and pathways of the inflammatory immune response.

Systemic inflammation after trauma.

Traumatic brain injury (TBI) is a significant problem in older adults. In persons aged 65 and older, TBI is responsible for more than 80,000 emergency department visits each year; three-quarters of these visits result in hospitalization as a result of the injury. Adults aged 75 and older have the highest rates of TBI-related hospitalization and death. Falls are the leading cause of TBI for older adults (51%), and motor vehicle traffic crashes are second (9%). Older age is known to negatively influence outcome after TBI. Although geriatric and neurotrauma investigators have identified the prognostic significance of preadmission functional ability, comorbidities, sex, and other factors such as cerebral perfusion pressure on recovery after illness or injury, these variables remain understudied in older adults with TBI. In the absence of good clinical data, predicting outcomes and providing care in the older adult population with TBI remains problematic. To address this significant public health issue, a refocusing of research efforts on this population is justified to prevent TBI in the older adult and to discern unique care requirements to facilitate best patient outcomes.

/pdf/traumatic-brain-injury-in-older-adults-epidemiology-outcomes-30hybhd44f.pdf

Traumatic Brain Injury in Older Adults: Epidemiology, Outcomes, and Future Implications

OBJECTIVE:: To determine the impact of the increasing aging population on trauma mortality relative to mortality from cancer and heart disease in the United States. BACKGROUND:: The population in the United States continues to increase as medical advancements allow people to live longer. The resulting changes in the leading causes of death have not yet been recognized. METHODS:: Data were obtained (2000-2010) from the Web-based Injury Statistics Query and Reporting System database of the Centers for Disease Control and Prevention. We defined trauma deaths as unintentional injuries, suicides, and homicides. RESULTS:: From 2000 to 2010, the US population increased by 9.7% and the number of trauma deaths increased by 22.8%. Trauma deaths and death rates deceased in individuals younger than 25 years but increased for those 25 years and older. During this period, death rates for cancer and heart disease decreased. The largest increases in trauma deaths were in individuals in their fifth and sixth decades of life. Since 2000, the largest proportional increase (118%) in crude trauma deaths occurred in 54-year-olds. Overall, in 2010, trauma was the leading cause of death in individuals 46 years and younger. Trauma remains the leading cause of years of life lost.Trauma is now the leading cause of death for individuals 46 years and younger. The largest increase in the number of trauma deaths and the highest crude number of trauma deaths occurred in baby boomers. Policy makers allocating resources should be made aware of the larger impact of trauma on our aging and burgeoning US population. Language: en

Increasing trauma deaths in the United States.

Background: As the population ages, the elderly will constitute a prominent proportion of trauma patients. The elderly suffer more severe consequences from traumatic injuries compared with the young, presumably resulting in increased resource use. In this study, we sought to examine ICU resource use in trauma on the basis of age and injury severity. Methods: This study was a retrospective review of trauma registry data prospectively collected on 26,237 blunt trauma patients admitted to all trauma centers (n = 26) in one state over 24 months (January 1996-December 1997). Age-dependent and injury severity-dependent differences in mortality, ICU length of stay (LOS), and hospital LOS were evaluated by logistic regression analysis. Results: Elderly (age ≥ 65 years, n = 7,117) patients had significantly higher mortality rates than younger (age 65 years was associ ated with a two- to threefold increases mortality risk in mild (ISS 30) have decreased ICU resource use secondary to associated increased mortality rates.

Trauma in the elderly: intensive care unit resource use and outcome.

Objective:To characterize the epidemiology of sepsis in trauma.Design:Analysis of a prospectively collected administrative database (Pennsylvania trauma registry).Setting:All trauma centers in the state of Pennsylvania (n = 28)Patients:All patients (n = 30,303) with blunt or penetrating injury admit

Epidemiology of sepsis in patients with traumatic injury.

Nosocomial pneumonia in trauma patients is a significant source of resource utilization and mortality. We have previously described increased rates of pneumonia in male trauma patients in a single institution study. In that study, female trauma patients had a lower incidence of postinjury pneumonia but a higher relative risk for mortality when they did develop pneumonia. We sought to investigate the hypothesis that male trauma patients have an increased incidence of postinjury pneumonia in a separate population-based dataset. Prospective data were collected on 30,288 trauma patients (26,231 blunt injuries, 4057 penetrating injuries) admitted to all trauma centers (n = 26) in Pennsylvania over 24 months (January 1996 to December 1997). Gender differences in pneumonia were determined for the entire dataset. A second analysis examined all blunt injury patients and excluded all patients with a hospital length of stay less than 24 h, eliminating patients who expired early after admission. In trauma patients with minor injury (ISS 15), male trauma patients had a significantly increased incidence of postinjury pneumonia (ISS 15-30, male 8.85%, female 6.45%; ISS > 30, male 24.35%, female 17.30%). Logistic regression analysis of blunt trauma patients revealed that gender, ISS, injury type, admission Revised Trauma Score (RTS), admission respiratory rate, history of cardiac disease, and history of cancer were all independent predictors of pneumonia. Trauma patients with nosocomial pneumonia had a significantly higher mortality rate (P < 0.001) than patients without pneumonia. There was no gender-specific difference in mortality among pneumonia patients. Male gender is significantly associated with an increased incidence of postinjury pneumonia. In contrast to our initial study, there was no gender difference in postinjury pneumonia mortality rates identified in this population-based study.

Male gender is associated with increased risk for postinjury pneumonia.

BACKGROUND: Women usually have lower mortality rates than men do at any age. This pattern is observed for most causes of death from chronic diseases. Significant controversy still exists about gender differences in outcomes in trauma. We previously reported no differences in in-hospital mortality based on gender in a large single-institution study (n = 18,892) that had a significant limitation in that it was not population based. This current study was performed to validate our earlier findings in a separate, statewide, population-based dataset of trauma victims. STUDY DESIGN: Prospective data were collected on 22,332 trauma patients (18,432 blunt, 3,900 penetrating) admitted to all trauma centers (n = 26) in Pennsylvania over 24 months (January 1996 to December 1997). Gender differences in in-hospital mortality were determined for the entire dataset and for the subsets of blunt and penetrating injury patients. A second analysis examined all blunt injury patients and excluded all patients with a hospital length of stay of less than 24 hours, eliminating patients who expired soon after admission. The null hypothesis was that female gender is protective in trauma outcomes. RESULTS: Multiple logistic regression analysis identified age (odds ratio [OR] 1.03, confidence interval [CI] 1.02 to 1.03), Injury Severity Score (OR 1.06, CI 1.05 to 1.06), non-Caucasian race (OR 1.72, CI 1.39 to 2.15), blunt injury type (OR 0.327, CI 0.26 to 0.41), and Revised Trauma Score (OR 0.44, CI 0.41 to 0.47) as independent predictors of in-hospital mortality in trauma. Preexisting diseases, including cardiac disease (OR 1.53, CI 1.12 to 2.09) and malignancy (OR 4.08, CI 1.64 to 10.17), were also identified as independent predictors of in-hospital mortality in trauma. Female gender was not associated with decreased mortality (OR 0.83, CI 0.67 to 1.03, p=0.093). A second multiple regression analysis in blunt trauma patients admitted for longer than 24 hours (which eliminated early deaths and patients with minor injuries) determined that in-hospital mortality was not significantly different in male or female blunt trauma patients stratified by Injury Severity Score and age. The same factors that were predictive of in-hospital mortality in the total dataset were also significant in this secondary analysis. CONCLUSIONS: These population-based data confirm that female gender does not adversely affect in-hospital mortality in trauma when patients are appropriately stratified for other variables, including Injury Severity Score and age, that do significantly affect outcomes.

https://www.journalacs.org/article/S1072-7515(02)01187-0/pdf

Michael Pasquale

Papers

Trauma in the elderly: intensive care unit resource use and outcome.

Epidemiology of sepsis in patients with traumatic injury.

Male gender is associated with increased risk for postinjury pneumonia.

A statewide population-based study of gender differences in trauma: validation of a prior single-institution study.