Association Between Health Insurance and Outcomes After Traumatic Brain Injury: A National ACS-TQP-PUF Database Study.

INTRODUCTION: According to the US Census Bureau, roughly 8.6% of the population lacks health care coverage. Increasing evidence suggests that insurance status plays a role in outcomes after trauma. However, its role in the setting of traumatic brain injury (TBI) remains poorly understood. METHODS: The Trauma Quality Programs Participant Use Files were queried from 2017 to 2019. All patients with isolated TBI were identified. Isolated TBI was defined as: 1) Head Abbreviated Injury Scale (AIS) > 3 and 2) AIS <3 in all other anatomical regions. Patients dead on arrival, with Head AIS = 6, or missing key data were excluded. Demographic and clinical information was compared between those with and without insurance. Multivariate regressions were used to assess associations between insurance status and TBI outcomes (inhospital mortality, discharge to facility, total ventilator days, Intensive Care Unit length of stay (ICU LOS), and hospital LOS). RESULTS: In total, 199,556 patients met inclusion criteria; 18,957 (9.5%) were uninsured. Compared to the insured, uninsured TBI patients were younger with a greater proportion of males. Uninsured patients were less severely injured and less comorbid. Uninsured patients had shorter unadjusted LOS in the ICU and hospital. Yet, uninsured patients experienced greater unadjusted inhospital mortality (12.7% versus 8.4%, P < 0.001). When controlling for covariates, lack of insurance was significantly associated with increased likelihood of mortality (OR 1.62; P < 0.001). This effect was most noticeable in patients with Head AIS = 4 (OR 1.55; P < 0.001) and Head AIS = 5 (OR 1.80; P < 0.001). Lack of insurance was also significantly associated with decreased likelihood of discharge to facility (OR 0.38), decreased ICU LOS (Coeff. -0.61), and decreased hospital LOS (Coeff. -0.82; all P < 0.001). CONCLUSIONS: This study demonstrates that insurance status is independently associated with outcome disparities after isolated TBI. Despite the Affordable Care Act (ACA) reform, lack of insurance appears significantly associated with inhospital mortality, decreased likelihood of discharge to facility, and decreased time spent in the ICU and hospital.

Preliminary Exploration of Long-Term Patient Outcomes After Tracheostomy in Burns: A Burn Model System Study.

INTRODUCTION: Upper airway management is crucial to burn care. Endotracheal intubation is often performed in the setting of inhalation injury, burns of the face and neck, or large burns requiring significant resuscitation. Tracheostomy may be necessary in patients requiring prolonged ventilatory support. This study compares long-term, patient-reported outcomes in burn patients with and without tracheostomy. MATERIALS AND METHODS: Data from the Burn Model System Database, collected from 2013 to 2020, were analyzed. Demographic and clinical data were compared between those with and without tracheostomy. The following patient-reported outcomes, collected at 6-, 12-, and 24-mo follow-up, were analyzed: Veterans RAND 12-Item Health Survey (VR-12), Satisfaction with Life, Community Integration Questionnaire, Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure, employment status, and days to return to work. Regression models and propensity-matched analyses were used to assess the associations between tracheostomy and each outcome. RESULTS: Of 714 patients included in this study, 5.5% received a tracheostomy. Mixed model regression analyses demonstrated that only VR-12 Physical Component Summary scores at 24-mo follow-up were significantly worse among those requiring tracheostomy. Tracheostomy was not associated with VR-12 Mental Component Summary, Satisfaction with Life, Community Integration Questionnaire, or Patient-Reported Outcomes Measurement Information System 29-Item Profile Measure scores. Likewise, tracheostomy was not found to be independently associated with employment status or days to return to work. CONCLUSIONS: This preliminary exploration suggests that physical and psychosocial recovery, as well as the ability to regain employment, are no worse in burn patients requiring tracheostomy. Future investigations of larger scale are still needed to assess center- and provider-level influences, as well as the influences of various hallmarks of injury severity. Nonetheless, this work should better inform goals of care discussions with patients and families regarding the use of tracheostomy in burn injury.

MenQuadfi (MenACWY-TT): A New Vaccine for Meningococcal Serogroups ACWY.

OBJECTIVE: This article reviews data encompassing the pharmacology, efficacy, and safety of MenACWY-TT (MenQuadfi), a conjugate vaccine to prevent meningococcal disease from serogroups A, C, W, Y. DATA SOURCES: A literature review was conducted in PubMed, MEDLINE, and ClinicalTrials.gov from inception up to July 2021, using the search terms MenQuadfi, meningococcal ACWY vaccine, MCV4, and menacwy. Articles from reference lists were included to identify potential relevant literature. STUDY SELECTION AND DATA EXTRACTION: Data were limited to randomized phase II and III clinical studies published in the English language, evaluating the efficacy and safety of MenACWY-TT. Animal studies and studies not utilizing MenACWY-TT were excluded. DATA SYNTHESIS: One phase II and 4 phase III randomized clinical studies, enrolling approximately 7700 participants, aged 2 years to 97 years old found that MenACWY-TT was noninferior when compared to established MenACWY vaccines, as measured by surrogate immunogenicity end points. In studies evaluating primary dose vaccination, conducted in those aged 2 to 97 years of age, the difference in seroresponse rates, reported by the lower bound of the 95% CI, was (A) 1.1% to 14.8%, (C) 21% to 42.2%, (Y) 7.7% to 24.6%, and (W) 8.9% to 22.5%. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Despite the low incidence of meningococcal disease in the United States, meningococcal disease causes significant morbidity and mortality if not prevented. CONCLUSION: MenACWY-TT is noninferior to currently approved quadrivalent meningococcal vaccines and shows similar immunogenicity and safety as both an initial vaccine for prevention as well as a booster dose.

Burn Injury Results in Myeloid Priming during Emergency Hematopoiesis.

INTRODUCTION: Hematopoiesis proceeds in a tiered pattern of differentiation, beginning with hematopoietic stem cells (HSC) and culminating in erythroid, myeloid, and lymphoid lineages. Pathologically altered lineage commitment can result in inadequate leukocyte production or dysfunctional cell lines. Drivers of emergency hematopoiesis after burn injury are inadequately defined. Burn injury induces a myeloid predominance associated with infection that worsens outcomes. This study aims to further profile bone marrow HSCs following burn injury in a murine model. METHODS: C57BL/6 mice received burn or sham injury with ~12% total body surface area (TBSA) scald burn on the dorsal surface with subsequent sacrifice at 1, 2, 3, 7 and 10 days post-injury. Bone marrow (BM) from hindlimbs were analyzed for HSC populations via flow cytometry and analyzed using FlowJo Software (version 10.6). Event counts and frequencies were analyzed with multiple unpaired t-tests and linear mixed-effect regression. RT-PCR performed on isolated lineage negative BM cell RNA targeted PU.1, GATA-1, and GATA-3 with subsequent analysis conducted with QuantStudio 3 software. Statistical analysis and representation were performed on GraphPad software (Prism). RESULTS: Flow cytometry revealed significantly elevated proportions of Long-Term HSCs at 3 days post-injury (p < .05) and Short-Term HSCs at days 2, 3, and 10 (all p < .05) in burn-injured mice. There was a sustained, but not significant, increase in proportions in the multi-potent progenitor (MPP) 2 and 3 subpopulations in the burn cohort compared to sham controls. The common myeloid progenitor (CMP) proportion was significantly higher on days 3 and 10 (both p < .01), while the granulocyte-macrophage progenitor (GMP) proportion increased on days 1, 2, and 10 (p < .05, p < .01, p < .01). Although the megakaryocyte-erythrocyte progenitor (MEP) proportion appeared consistently lower in the burn cohort, this did not reach significance. mRNA analysis resulted in a downregulation of PU.1 on day 1 (p = 0.0002) with an upregulation by day 7 (p < 0.01). GATA-1 downregulation occurred by day 7 (p < 0.05), and GATA3 showed downregulation on days 3 and 7 (p < 0.05). DISCUSSION: Full-thickness burn results in an emergency hematopoiesis via proportional increase of Long Term-HSC and Short Term-HSC/MPP1 subpopulations beginning in the early post-injury period. Subsequent lineage commitment displays a myeloid predominance with a shift toward myeloid progenitors with mRNA analysis corroborating this finding with associated upregulation of PU.1 and downregulation of GATA-1 and GATA-3. Further studies are needed to understand how burn-induced emergency hematopoiesis may predispose to infection by pathologic lineage selection.

A nationwide analysis of geriatric proximal humerus fractures: trends, outcomes, and cost.

Background: In the USA, proximal humerus fractures (PHF) are the third most common fracture among the elderly. Although most geriatric PHF are treated conservatively, surgical management remains an option. This retrospective study compares annual trends, patient outcomes, and hospital costs between operatively and non-operatively managed geriatric PHF. Methods: The Healthcare Cost and Utilization Project Nationwide Inpatient Sample was queried from 2012 to 2015. Geriatric patients with PHF were identified and those who underwent operative or non-operative management were compared in trends, outcomes and costs. Results: In total, 137 810 patients met inclusion criteria, of which 51 795 (37.6%) underwent operative management. The operative cohort was younger (76.6 vs 80.9, p<0.001) with a greater proportion of females (81.8% vs 77.6%, p<0.001). The operative cohort demonstrated less frailty and lower Elixhauser Comorbidity Scores (both p<0.001). The operative cohort was also more likely to be discharged home (30.4% vs 13.9%, p<0.001). There was no significant linear trend in age-adjusted and sex-adjusted proportions of operative versus non-operative geriatric PHF (p=0.071), but a positive linear trend was statistically significant for total cost of operative geriatric PHF (p<0.001). Multivariable analyses demonstrated similar overall complication rates between cohorts (OR 0.95, 95% CI 0.89 to 1.00; p=0.06), although surgical intervention increased length of stay (LOS) by 0.15 days (95% CI 0.03 to 0.27; p<0.001) and median cost of hospitalization by US$10 684 (95% CI US$10 384 to US$10 984; p<0.001). Conclusions: This study identifies a positive linear trend in total cost of operatively managed geriatric PHF from 2012 to 2015. Operative management of geriatric PHF is associated with a similar overall complication rate and greater likelihood of being discharged home. Although non-operative management is associated with decreased LOS and hospital expenses, providers should consider surgical PHF treatment options when available and appropriate in the context of patient-focused outcomes, particularly long-term disposition after intervention. Level of Evidence: This level IV retrospective study identifies.

TRAUMATIC BRAIN INJURY-INDUCED INFLAMMATION AND GASTROINTESTINAL MOTILITY DYSFUNCTION.

ABSTRACT: Background: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States, with an annual cost of 60 billion dollars. There is evidence suggesting that in the post-TBI period, the gastrointestinal tract plays a central role in driving organ and immune dysfunction and may be the source of increased circulating proinflammatory mediators. In this study, we examined systemic inflammation and bacterial dysbiosis in patients who sustained a TBI with or without polytrauma. Using a mouse model of TBI, we further show how neuroinflammation after TBI is potentially linked to disruptions in gut homeostasis such as intestinal transit and inflammation. Methods: During a study of trauma patients performed from September 1, 2018, to September 1, 2019, at a single, level 1 trauma center, TBI patients aged 21 to 95 years were enrolled. Patients were categorized as TBI based on evidence of acute abnormal findings on head computed tomographic scan, which was a combination of isolated TBI and TBI with polytrauma. Blood and stool samples were collected between 24 h and 3 days after admission. Twelve plasma samples and 10 fecal samples were used for this study. Healthy control samples were obtained from a healthy control biobank. We examined systemic inflammation and bacterial changes in patients who sustained a TBI. In addition, TBI was induced in 9- to 10-week-old male mice; we assessed neuroinflammation, and intestine transit (motility) and bacterial changes 24 h after TBI. Results: When compared with healthy controls, TBI patients had increased systemic inflammation as evidenced by increased levels of IFN-γ and MCP-1 and a trend toward an increase of IL-6 and IL-8 ( P = 0.0551 and P = 0.0549), respectively. The anti-inflammatory cytokine, IL-4, was also decreased in TBI patients. Although there was a trend of an increase in copy number of Enterobacteriaceae and a decrease in copy number of Lactobacillus in both patients and mice after TBI, these trends were not found to be significantly different. However, TBI significantly increased the copy number of another potential pathogenic bacteria Bilophila wadsworthia in TBI patients compared with healthy controls. After a moderate TBI, mice had increased expression of TNF-α, IL-6 and IL-1ß, CXCL1, s100a9, and Ly6G and decreased IL-10 in the brain lesion after TBI. This accompanied decreased transit and increased TNF-α in the small intestine of mice after TBI. Conclusions: Our findings suggest that TBI increases systemic inflammation, intestinal dysfunction, and neuroinflammation. More studies are needed to confirm whether changes in intestinal motility play a role in post-TBI neuroinflammation and cognitive deficit.

The Effect of Distance to Treatment Center on Long-Term Outcomes of Burn Patients.

Geospatial proximity to American Burn Association (ABA)-verified burn centers or self-designated burn care facilities varies across the country. This study evaluates the effect of distance to treatment center on long-term, patient-reported outcomes. Data from the Burn Model System (BMS) National Longitudinal Database were analyzed. Demographic and clinical data were compared between three cohorts stratified by distance to BMS center (<20, 20-49.9, ≥50 miles). Distance to BMS center was calculated as driving distance between discharge and BMS center ZIP code centroids. The following patient-reported outcomes, collected at 12-months follow-up, were examined: Veterans RAND 12-Item Health Survey (VR-12), Satisfaction with Life (SWL) scale, employment status, and days to return to work. Mixed model regression analyses were used to examine the associations between distance to BMS center and each outcome, controlling for demographic and clinical variables. Of 726 patients included in this study, 26.3% and 28.1% were <20 and between 20 and 49.9 miles to a BMS center, respectively; 46.6% were ≥50 miles to a BMS center. Greater distance was associated with white/non-Hispanic race/ethnicity, preinjury employment, flame injury, and larger burn size (P < .001). Regression analyses did not identify significant associations between distance to BMS center and any patient-reported outcomes. This study suggests that patients treated at BMS centers have similar long-term, patient-reported outcomes of physical and psychosocial function, as well as employment, despite centralization of burn care and rehabilitation services. Given a steady decline in the incidence of burn injury, continued concentration of key resources is logical and safe.

American Burn Association (ABA) Burn Care Quality Platform (BCQP) and Large Data Set Analysis Considerations: A Practical Guide to Investigating Clinical Questions in Burns via Large Data Sets.

The Burn Care Quality Platform (BCQP) consolidates data previously collected from the National Burn Repository and the Burn Quality Improvement Program into a single registry. Its data elements and their associated definitions are tailored to create consistency across other national trauma registries, namely the National Trauma Data Bank implemented by the American College of Surgeons Trauma Quality Improvement Program (ACS TQIP). The BCQP now includes 103 participating burn centers and has captured data from 375,000 total patients as of 2021. With 12,000 patients entered under the current data dictionary, the BCQP represents the largest registry of its kind. On behalf of the American Burn Association Research Committee, the aim of this whitepaper is to provide a succinct overview of the BCQP, showcasing its unique features, strengths, limitations, and relevant statistical considerations. This whitepaper will highlight the resources available to the burn research community and offer insight on proper study design when preparing to conduct a large data set investigation for burn care. All recommendations herein were formulated through the consensus of a multidisciplinary committee and based on the available scientific evidence.

A multicenter validation of the modified brain injury guidelines: Are they safe and effective?

BACKGROUND: The modified Brain Injury Guidelines (mBIG) are an algorithm for treating patients with traumatic brain injury and intracranial hemorrhage by which selected patients do not require a repeat head computed tomography, a neurosurgery consult, or even an admission. The mBIG refined the original Brain Injury Guidelines (BIG) to improve safety and reproducibility. The purpose of this study is to assess safety and resource utilization with mBIG implementation. METHODS: The mBIG were implemented at three Level I trauma centers in August 2017. A multicenter retrospective review of prospectively collected data was performed on adult mBIG 1 and 2 patients. The post-mBIG implementation period (August 2017 to February 2021) was compared with a previous BIG retrospective evaluation (January 2014 to December 2016). RESULTS: There were 764 patients in the two study periods. No differences were identified in demographics, Injury Severity Score, or admission Glasgow Coma Scale score. Fewer computed tomography scans (2 [1,2] vs. 2 [2,3], p < 0.0001) and neurosurgery consults (61.9% vs. 95.9%, p < 0.0001) were obtained post-mBIG implementation. Hospital (2 [1,4] vs. 2 [2,4], p = 0.013) and intensive care unit (0 [0,1] vs. 1 [1,2], p < 0.0001) length of stay were shorter after mBIG implementation. No difference was seen in the rate of clinical or radiographic progression, neurosurgery operations, or mortality between the two groups.After mBIG implementation, eight patients (1.6%) worsened clinically. Six patients that clinically progressed were discharged with Glasgow Coma Scale score of 15 without needing neurosurgery intervention. One patient had clinical and radiographic decompensation and required craniotomy. Another patient worsened clinically and radiographically, but due to metastatic cancer, elected to pursue comfort measures and died. CONCLUSION: This prospective validation shows the mBIG are safe, pragmatic, and can dramatically improve resource utilization when implemented. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Matrix Metalloproteinases and Their Inhibitors and Proteoglycan 4 in Patients Undergoing Total Joint Arthroplasty.

Osteoarthritis, a degenerative disease of the joints, is the most common form of arthritis in the knee. Total joint arthoplasty is a commonly used treatment for joint degeneration and osteoarthritis, and due to these factors, TJA for hip and knee joints is projected to grow by 137% and 601% between 2005 and 2030. Matrix metalloproteases are enzymes found in the extracellular matrix that cleave matrix components. Normally MMPs are downregulated in tissues by Tissue Inhibitors of Metalloproteases, or TIMPs. The relative concentration of TIMPs also may denote some of the activity of the MMPs found in serum. Lubricin (proteoglycan 4) is a molecule found in the synovial fluid that protects joints by dissipating strain energy during locomotion. Lubricin synovial fluid concentration is also diminished in many patients with osteoarthritis, but not all. Given the importance of these three sets of molecules, our lab investigated the correlation between circulating lubricin, MMP levels and TIMPs levels. Blood plasma samples were obtained from de-identified subjects undergoing total joint arthroplasty at Loyola University Medical Center and the University of Utah. Normal blood plasma from pooled healthy individuals served as a control. We analyzed biomarker levels in plasma using ELISA. Our data show that MMP-1 and 9 were increased in TJA patients compared to normal controls, while MMP-2 and 13 were decreased. We also found decreased lubricin and tissue factor in surgical patients relative to controls. These data support the idea that lubricin is vital in protecting the synovial joint and that MMPs play a complex role in the destruction of the joint.

Inflammatory Biomarker Profiling in Total Joint Arthroplasty and Its Relevance to Circulating Levels of Lubricin, a Novel Proteoglycan.

Lubricin, also known as proteoglycan 4, acts as an antiadhesive and boundary lubricant to prevent cartilage damage in healthy joints. Following injury, a decrease in synovial fluid (SF) lubricin may lead to secondary osteoarthritis (OA). Inflammatory biomarkers, such as IL-1ß and TNF-α, are also implicated in the pathophysiology of OA. Interestingly, they have been shown to suppress the expression and secretion of lubricin in SF. This study aims to compare circulating levels of inflammatory biomarkers and lubricin between total joint arthroplasty (TJA) patients and healthy individuals. Doing so may better elucidate their roles in OA and extend the understanding of inflammation as a regulator of lubricin. Deidentified plasma samples were obtained 1 day preoperatively and 1 day postoperatively from patients undergoing TJA. Utilizing biochip array technology, they were profiled for IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-γ, IL-1α, IL-1ß, MCP-1, EGF, and TNF-α. Circulating lubricin levels were also measured using enzyme-linked immunosorbent assay. Compared to healthy controls, IL-6, IL-8, VEGF, IL-1ß, MCP-1, EGF, and TNF-α were significantly increased pre- and postoperatively. Lubricin was significantly decreased. This may indicate that elevations in inflammatory cytokines initiate a cascade of events, leading to decreased lubricin, which places the joint at increased risk of developing OA.