Candidate Genetic and Molecular Drivers of Dysregulated Adaptive Immune Responses After Traumatic Brain Injury.

Abstract Neuroinflammation is a significant and modifiable cause of secondary injury after traumatic brain injury (TBI), driven by both central and peripheral immune responses. A substantial proportion of outcome after TBI is genetically mediated, with an estimated heritability effect of around 26%, but because of the comparatively small datasets currently available, the individual drivers of this genetic effect have not been well delineated. A hypothesis-driven approach to analyzing genome-wide association study (GWAS) datasets reduces the burden of multiplicity testing and allows variants with a high prior biological probability of effect to be identified where sample size is insufficient to withstand data-driven approaches. Adaptive immune responses show substantial genetically mediated heterogeneity and are well established as a genetic source of risk for numerous disease states; importantly, HLA class II has been specifically identified as a locus of interest in the largest TBI GWAS study to date, highlighting the importance of genetic variance in adaptive immune responses after TBI. In this review article we identify and discuss adaptive immune system genes that are known to confer strong risk effects for human disease, with the dual intentions of drawing attention to this area of immunobiology, which, despite its importance to the field, remains under-investigated in TBI and presenting high-yield testable hypotheses for application to TBI GWAS datasets.

The Epidemiology of Lower Limb Fractures: A Major United Kingdom (UK) Trauma Centre Study.

INTRODUCTION: Understanding the epidemiology and incidence of fractures can help inform policymakers and clinicians about the needs of the population and highlight trends over time, allowing for tailoring of healthcare delivery to the population. This study reports on the lower limb fractures treated at a major trauma centre over a seven-year period. METHODS: We collected data on fracture locations, age, gender, BMI, hospital admission length, and treatment options of all lower limb fractures treated at a level I trauma centre from January 2015 to December 2021. We included data on the femur, tibia, and fibula, which were each split up into distinct regions. Fractures were subdivided by location and graphed, separated by gender, over age group. Finally, each location area's frequency was graphed over the entire study period. RESULTS: A total of 8,511 patients sustained 8,613 fractures, given an overall incidence of 215.9 fractures per 100,000 patients per year. The mean age was 62.3 years, and 56.3% of patients were female. Fractures of the peri trochanteric region of the femur had the highest mean average age (79.9 years), which was closely followed by fractures of the head and neck of the femur (78.2 years). Fractures of the head and neck of the femur and the peri trochanteric region of the femur also had the highest proportion of females suffering from these fractures (67 and 66% female, respectively). Femur shaft fractures had the lowest average age (36.5 years) and the lowest proportion of female patients (29%). On graphing by location, separated by gender, over age group, overall fractures showed a bi-peak distribution of younger males and older, post-menopausal females having their respective peaks. Three further distinct distributions were observed in individual location fractures. CONCLUSION: Identifying the relative incidence and demographic associations with lower limb fractures helps highlight a changing population's needs. There is an absence of such study in literature in the United Kingdom (UK) since 2006. Our study's insights and results aid clinicians and policymakers in the creation of guidelines and the distribution of resources based on the most recent information and elucidate changing healthcare service needs for the population.

Epidemiology and Incidence of Upper Limb Fractures: A UK Level 1 Trauma Center Perspective.

Introduction Understanding the incidence and epidemiology can inform clinicians and policymakers about the population's needs. Our study reports on upper limb fractures treated at a major trauma center over 7.5 years. Methods  We collected data on fracture locations, age, gender, Charlson Comorbidity index (CCI), and treatment options of all upper limb fractures treated at a Level I Trauma Centre from January 1, 2015 to June 30, 2022. Humerus, radius, and ulna fractures were each classified as proximal, diaphyseal, and distal. Results About 9,915 patients sustained 12,790 fractures, given an overall incidence of 303.2 fractures per 100,000 patients per year. The most common fracture site was the distal radius (60.1 fractures per 100,000 patients per year, whereas carpal and metacarpal bones had the lowest incidence. The mean age and CCI were 46.4 years and 1.54, respectively. 58.1% of patients were male. All bone fractures distal to the elbow were associated with an age younger than the mean (all p<0.001), with humerus fracture patients having the oldest mean age (54.6 years). Compared to the mean gender ratio, except for ulna (no association), humerus (55% female), and radius (51% female), all other locations showed significantly higher incidences of males (all p<0.001). When plotting the incidence based on the age of injury, the entire cohort, along with radius and ulna fracture subgroups, demonstrated a bi-peak distribution. This pattern revealed that younger males and older postmenopausal females had the highest incidence rates. Conclusion To our knowledge, this represents the first study of this type in the UK since 2006. We sought to elucidate relative incidence and demographic associations with fractures to highlight changing population needs and allow policymakers and services at a regional and national level to operate with up-to-date information.

Factors Affecting Upper Limb Fracture Opioid Requirements.

Introduction Understanding the different opioid pain relief requirements between patients with upper limb fractures can be useful in forming specific evidence-based guidelines and balancing patient-clinician prescribing discussions with opioid stewardship. We investigated the predictors for opioid requirements in upper limb fractures. Methods We retrospectively investigated all upper limb fractures from the shoulder to the wrist treated at a major trauma center from January 2015 to January 2022. The data collected consisted of fracture location, demographics, comorbidities, and management options. Post-injury opioid prescriptions in the first post-injury year were calculated every month up to six months and then grouped from the seventh to the 12th month and converted to morphine milligram equivalents (MMEs). We then calculated days requiring at least one medication (representing the "coverage") and relative "strength" in each time period. Results Six thousand four hundred thirteen patients sustaining a combined 9125 fractures were included in the study, with an MME mean of 436. Fracture locations of the scapula, proximal humerus, humeral shaft, distal humerus, and proximal ulna all had significantly higher MME requirements (p<0.05) at the one-year level. The radius shaft and distal radius had significantly lower MME requirements (p<0.05). The patients with depression, diabetes, drug abuse history, obesity, pulmonary circulatory disorder, and rheumatological conditions required higher strength of opioids at the one-year level (p<0.05). The patients with chronic kidney disease, depression, pulmonary circulation disorder, and rheumatological conditions required higher coverage of opioids at the one-year level (p<0.05). Conclusion Our study presents a high-resolution breakdown of the post-injury opioid requirements for patients with upper limb injuries. Fractures of the scapula, proximal humerus, and shaft of the humerus were associated with increases in both opioid strength and coverage. Depression, pulmonary disease, and rheumatological conditions were all associated with increased opioid strength and coverage. This provides a framework for which clinicians and patients can more accurately anticipate the course of the rehabilitation journey and risk stratify appropriately at the outset of injury.