Subsequent Injury Research Articles

A-29 To report or not to report: A review of adolescent decision-making theories following sports-related concussion

Abstract Purpose Sports-related concussion (SRC) is a prevalent concern among adolescent athletes. If SRC is suspected, athletes are usually removed from play for assessment and symptom monitoring. Return-to-play decisions heavily rely on athlete self-report of SRC and associated symptoms. Social pressures and attitudes related to symptom reporting influence an athlete’s decision of whether to disclose symptoms; not reporting increases risk for subsequent injury and delayed recovery. Therefore, it is important to understand the adolescent decision-making process following SRC. In this review, prevailing theories that explain symptom reporting and decision-making following SRC will be evaluated from a clinical lens. Data Selection Literature was reviewed using Google Scholar, PubMed, and SCOPUS. Search terms included “concussion” AND “sport” AND “symptom reporting” OR “reporting” OR “self-report”. Other terms included “decision-making”, “disclosure”, “adolescent”, “high school”, and “college”. Articles from 2004-2023 were included. Data Synthesis Three prevailing theories have been proposed to explain symptom underreporting among adolescent athletes: the Theory of Reasoned Action and Planned Behavior, the Bandura Social Cognitive Theory, and the Disclosure Decision-Making Model. These theories will be critiqued and the lack of research on neurodevelopmental components of decision-making will be highlighted. Conclusions The decision-making process following SRC is complex, multi-factorial, and state-dependent. While these theories provide critical insights into symptom reporting following SRC, they do not consider important neurodevelopmental factors such as the imbalance between cognitive control and reward processing in adolescence. When educating parents and coaches about symptom reporting following SRC, it will be important for clinicians to consider socioemotional, cultural, environmental, and neurodevelopmental factors.

#4337 UPDATED INTERIM RESULTS OF A PHASE 1/2 STUDY OF BION-1301 IN PATIENTS WITH IGA NEPHROPATHY

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the leading cause of primary glomerulonephritis worldwide with limited treatment options, especially for high-risk patients. Approximately 30-45% of IgAN patients progress to end-stage kidney disease over a period of 20-25 years and proteinuria is the strongest predictor of disease progression [1]. BION-1301 is a novel humanized monoclonal antibody that blocks a proliferation-inducing ligand (APRIL), a cytokine that is elevated in patients with IgAN. APRIL promotes the production of pathogenic galactose-deficient IgA1 (Gd-IgA1), leading to immune complex deposition and subsequent kidney injury. Blocking APRIL with BION-1301 is a potential disease-modifying approach to directly target the pathogenesis of IgAN. In a Phase 1/2 study (NCT 03945318) in healthy volunteers and patients with IgAN, BION-1301 was well-tolerated with no serious adverse events (SAEs) and durably reduced free APRIL, IgA, Gd-IgA1, IgM and to a lesser extent, IgG [2]. Method For the ongoing phase 1/2 open-label, multicohort trial, eligibility criteria include adults with biopsy-proven IgAN, eGFR ≥30 mL/min per 1.73 m2, baseline urine protein excretion ≥0.5 g/24 hrs or UPCR ≥0.5 g/g, and on stable/optimized RASi (or intolerant). Cohort 1 received 450 mg of BION-1301 administered IV every 2 weeks, transitioning to SC at 600 mg every 2 weeks after at least 24 weeks. Cohort 2 receives 600 mg of BION-1301 SC every 2 weeks. Results In both Cohorts 1 and 2, BION-1301 was generally well-tolerated, with no SAEs or terminations due to AEs as of the last reported interim analysis (November 2022) [2]. Durable reductions in serum levels of free APRIL and immunoglobulins were observed in both cohorts. No anti-drug antibodies have been observed in patients with IgAN to date. In Cohort 1, clinically meaningful reductions in proteinuria were seen as early as 12 weeks (30.4% geometric mean UPCR reduction, n = 7), and were sustained through 24 weeks (48.8% geometric mean UPCR reduction, n = 8) and 52 weeks (66.9% geometric mean UPCR reduction, n = 8). Reductions in proteinuria were consistent in Cohort 2 (53.8% geometric mean UPCR reduction, n = 9) at 24 weeks. Significant and durable reductions in serum Gd-IgA1 concentrations were observed and were consistent across both cohorts. Updated data will be reported at the time of presentation. Conclusion BION-1301 offers disease-modifying potential by directly targeting the initiating pathogenesis of IgAN. Interim biomarker and clinical activity responses support advancement of BION-1301 into later-stage development for patients with IgAN.

Dynamic postural control in injured collegiate cross-country runners is not associated with running-related injury

BackgroundBiomechanical factors have been associated with running-related injury, but associations are unclear. Dynamic postural stability may be a factor related to injury that has not been studied extensively. Research questionDoes dynamic postural control differ in those with a history of running-related injury or those who go on to sustain a running-related injury? MethodsSixty-five (45 injured; 20 uninjured) and fifty-eight (13 injured; 45 uninjured) collegiate cross-country runners were available for our retrospective and prospective analyses. Time to stabilization and dynamic postural stability index were collected during two separate jump landing tasks (forward and lateral direction) for each leg. Retrospective injury was tabulated by a running history survey. Prospective injuries were recorded by a licensed athletic trainer during the competitive season. Differences in postural stability were compared between injured and uninjured groups and between limbs using two-way ANOVA’s. An overall group by leg comparison was completed for each task. ResultsThe non-dominant limb demonstrated better postural stability indices regardless of injury history. An interaction was observed between limbs and history of injury for the anterior-posterior time to stabilization for the lateral task. The non-dominant limb demonstrated better medio-lateral postural stability indices and time to stabilization during the lateral task, regardless of prospective injury. SignificanceDynamic postural stability was reduced in the dominant limb, but no clear differences were seen between injured and uninjured runners. This suggests dynamic postural stability may be altered in individuals with a history of a running-related injury, but no relationship to subsequent injury was substantiated. Further work is needed to understand how dynamic postural stability may be related to running-related injury.

Arteriovenous fistula in a renal allograft with gross hematuria and subsequent acute kidney injury due to urinary tract obstruction: a case report

BackgroundArteriovenous fistula (AVF) due to renal allograft biopsy is mechanical trauma resulting from the penetration of small arteries and veins by a core needle. Most AVFs are reported to resolve asymptomatically and spontaneously. This report presents a patient with acute kidney injury (AKI) due to urinary tract obstruction caused by a bleeding AVF in a renal allograft.Case presentationA 22-year-old Japanese woman who underwent living-donor kidney transplantation (KT) at 3 years due to end-stage renal disease caused by focal segmental glomerulosclerosis (FSGS) presented with a renal transplant AVF (gourd-shaped; 42 × 19 × 20 mm). The AVF was unexpectedly discovered by ultrasound before a surveillance biopsy at 10 years after KT. The patient had a history of recurrent FSGS, had undergone several renal allograft biopsies after KT, and did not experience symptoms or growth of the AVF for years. Nineteen years after KT, the patient developed AKI with sudden, asymptomatic, gross hematuria and anuria. Plain computed tomography revealed a hematoma in the pelvis of the renal allograft and bladder tamponade. The AVF was successfully treated by coil embolization. Hemodialysis was performed for AKI, and graft function was gradually recovered.ConclusionsUnexpected bleeding from a renal transplant AVF may lead to transplant dysfunction. Angiographic embolization against the ruptured renal transplant AVF may prevent rebleeding and rescue the renal allograft.

Preeclampsia up to date-What's going on?

Preeclampsia is a hypertensive disorder in pregnancy characterized by placental malperfusion and subsequent multi-organ injury. It accounts for approximately 14% of maternal deaths and 10-25% of perinatal deaths globally. In addition, preeclampsia has been attracting attentions for its association with risks for developing chronic diseases in later life for both mother and child. This mini-review discusses on latest knowledge on prediction, prevention, management, and long-term outcomes of preeclampsia and also touches on association between COVID-19 and preeclampsia. HTN hypertension, HDP hypertensive disorders of pregnancy, PE preeclampsia, BP blood pressure, cfDNA cell-free DNA, ST2 human suppression of tumorigenesis 2, sFlt-1 soluble fms-like tyrosine kinase-1, PIGF placental growth factor, VEGF vascular endothelial growth factor, VEGFR VEGF receptor, TGFβ transforming growth factor β, ENG endoglin, sENG soluble ENG, PRES posterior reversible encephalopathy syndrome, AKI acute kidney injury, CVD cardiovascular disease, ESKD end-stage kidney disease, ACE angiotensinogen converting enzyme, Ang angiotensin.

Prediction of In-Hospital Falls Using NRS, PACD Score and FallRS: A Retrospective Cohort Study.

Harmful in-hospital falls with subsequent injuries often cause longer stays and subsequently higher costs. Early identification of fall risk may help in establishing preventive strategies. To assess the predictive ability of different clinical scores including the Post-acute care discharge (PACD) score and nutritional risk screening score (NRS), and to develop a new fall risk score (FallRS). A retrospective cohort study of medical in-patients of a Swiss tertiary care hospital from January 2016 to March 2022. We tested the ability of the PACD score, NRS and FallRS to predict a fall by using the area under curve (AUC). Adult patients with a length of stay of ≥ 2 days were eligible. We included 19,270 admissions (43% females; median age, 71) of which 528 admissions (2.74%) had at least one fall during the hospital stay. The AUC varied between 0.61 (95% confidence interval (CI), 0.55-0.66) for the NRS and 0.69 (95% CI, 0.64-0.75) for the PACD score. The combined FallRS score had a slightly better AUC of 0.70 (95% CI, 0.65-0.75) but was more laborious to compute than the two other scores. At a cutoff of 13 points, the FallRS had a specificity of 77% and a sensitivity of 49% in predicting falls. We found that the scores focusing on different aspects of clinical care predicted the risk of falls with fair accuracy. A reliable score with which to predict falls could help in establishing preventive strategies for reducing in-hospital falls. Whether or not the scores presented have better predictive ability than more specific fall scores do will need to be validated in a prospective study.

Injectable hydrogels in central nervous system: Unique and novel platforms for promoting extracellular matrix remodeling and tissue engineering.

Repairing central nervous system (CNS) is difficult due to the inability of neurons to recover after damage. A clinically acceptable treatment to promote CNS functional recovery and regeneration is currently unavailable. According to recent studies, injectable hydrogels as biodegradable scaffolds for CNS tissue engineering and regeneration have exceptionally desirable attributes. Hydrogel has a biomimetic structure similar to extracellular matrix, hence has been considered a 3D scaffold for CNS regeneration. An interesting new type of hydrogel, injectable hydrogels, can be injected into target areas with little invasiveness and imitate several aspects of CNS. Injectable hydrogels are being researched as therapeutic agents because they may imitate numerous properties of CNS tissues and hence reduce subsequent injury and regenerate neural tissue. Because of their less adverse effects and cost, easier use and implantation with less pain, and faster regeneration capacity, injectable hydrogels, are more desirable than non-injectable hydrogels. This article discusses the pathophysiology of CNS and the use of several kinds of injectable hydrogels for brain and spinal cord tissue engineering, paying particular emphasis to recent experimental studies.

Gymnastics and concussions: A retrospective chart review

ABSTRACT Objective The purpose of this study was to investigate the clinical presentation (using PCSS), mechanism of injury, and recovery time of concussions sustained by gymnasts. Methods A retrospective chart review was performed at Boston Children’s Hospital: Sports Medicine Clinic. Patients were identified with the words ‘gymnastics’ and ‘concussion.’ Male and female gymnasts were included if they sustained a concussion during gymnastics training or competition and were between the ages of 6–22 years old. Sex, age, injury site, diagnosis, mechanism of injury, and time to presentation are described. Patients were compared during different types of gymnastics events for overall symptom burden, and individual symptom severities. Results A total of 201 charts were assessed over a 6-year period and 62 patients met inclusion criteria. Floor exercise was the most common event at the time of injury. Loss of consciousness occurred in 20% of injuries. There was no significant association between the type of event and PCSS upon initial clinical visit (p = 0.82). A total of 13 gymnasts returned to the clinic for a subsequent injury after their concussion (Table 3). Conclusions Gymnasts are at risk for sport-related concussions. Most gymnasts reporting to a tertiary care center with the diagnosis of concussion sustain their injuries during floor exercise.

The use of whole-body trauma CT should be based on mechanism of injury: A risk analysis of 3920 patients at a tertiary trauma centre

BackgroundMechanism of injury (MOI) plays a significant role in a decision to perform whole-body computed tomography (CT) imaging for trauma patients. Various mechanisms have unique patterns of injury and therefore form an important variable in decision making. MethodsRetrospective cohort study including all patients >18 years old who received a whole-body CT scan between 1 January 2019 and 19 February 2020. The outcomes were divided into CT ‘positive’ if any internal injuries were detected and CT ‘negative’ if no internal injuries were detected. The MOI, vital sign parameters, and other relevant clinical examination findings at presentation were recorded. Results3920 patients met the inclusion criteria, of which 1591 (40.6%) had a positive CT. The most common MOI was fall from standing height (FFSH), accounting for 23.0%, followed by motor vehicle accident (MVA), accounting for 22.4%. Covariates significantly associated with a positive CT included age, MVA >60 km/h, motor bike, bicycle, or pedestrian accident >30 km/h, prolonged extrication >30 min, fall from height above standing, penetrating chest or abdominal injury, as well as hypotension, neurological deficit, or hypoxia on arrival. FFSH was shown to reduce the risk of a positive CT overall, however, sub-analysis of FFSH in patients >65 years showed a significant association with a positive CT (OR 2.34, p < 0.001) compared to <65 years. ConclusionsPre-arrival information including MOI and vital signs have significant impact on identifying subsequent injuries with CT imaging. In high energy trauma, we should consider the need for whole-body CT based on MOI alone regardless of the clinical examination findings. However, for low-energy trauma, including FFSH, in the absence of clinical examination findings which support an internal injury, a screening whole-body CT is unlikely to yield a positive result, particularly in the age group <65yo.

Dietary (Poly)phenols in Traumatic Brain Injury.

Traumatic brain injury (TBI) remains one of the leading causes of death and disability in young adults worldwide. Despite growing evidence and advances in our knowledge regarding the multifaceted pathophysiology of TBI, the underlying mechanisms, though, are still to be fully elucidated. Whereas initial brain insult involves acute and irreversible primary damage to the brain, the processes of subsequent secondary brain injury progress gradually over months to years, providing a window of opportunity for therapeutic interventions. To date, extensive research has been focused on the identification of druggable targets involved in these processes. Despite several decades of successful pre-clinical studies and very promising results, when transferred to clinics, these drugs showed, at best, modest beneficial effects, but more often, an absence of effects or even very harsh side effects in TBI patients. This reality has highlighted the need for novel approaches that will be able to respond to the complexity of the TBI and tackle TBI pathological processes on multiple levels. Recent evidence strongly indicates that nutritional interventions may provide a unique opportunity to enhance the repair processes after TBI. Dietary (poly)phenols, a big class of compounds abundantly found in fruits and vegetables, have emerged in the past few years as promising agents to be used in TBI settings due to their proven pleiotropic effects. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by a state-of-the-art summary of the studies that have evaluated the efficacy of (poly)phenols administration to decrease TBI-associated damage in various animal TBI models and in a limited number of clinical trials. The current limitations on our knowledge concerning (poly)phenol effects in TBI in the pre-clinical studies are also discussed.

Opportunities for preventing subsequent injuries: a qualitative study exploring perspectives of people who have experienced injuries.

This study aims to examine opportunities for subsequent injury prevention from the perspectives of people who have recently experienced subsequent injury events. This qualitative study involved individual semi-structured interviews with people who had >2 injury events in the previous 12 months. Interviews were audio-recorded, transcribed verbatim and thematic analysis undertaken. Sixteen interviews were completed with participants who had experienced a range of index and subsequent injury types. Potential opportunities raised were wide-ranging. Some related to individuals, e.g., motivation to carry out prevention strategies. Other opportunities were related to healthcare providers and the health system. For instance, increasing consultation times to allow a focus on subsequent injury prevention, building rapport and tailoring their approach to the individual, proactively referring people to a range of healthcare providers, and ensuring people are aware of resources and supports available following injury. Broader environmental and societal opportunities were also suggested, such as ensuring adequate social support following injury, ensuring accessibility to rehabilitation and community facilities and the modification of built environments. A broad range of potential opportunities to prevent subsequent injuries were raised. These opportunities are promising and future research to trial interventions raised in this study is warranted to determine their feasibility and effectiveness.

Inhibition of lysophosphatidic acid receptor 1 relieves PMN recruitment in CNS via LPA1/TSP1/CXCR2 pathway and alleviates disruption on blood-brain barrier following intracerebral haemorrhage in mice

BackgroudThe frequencies of morbidity and impairment associated with spontaneous intracerebral haemorrhage (ICH) are comparatively high. Blood-brain barrier (BBB) integrity was compromised due to subsequent brain injury induced by ICH, which is crucial for a poor prognosis. Polymorphonuclear leukocyte (PMN) strongly modulate the disruption of BBB in the central nervous system (CNS). The lysophosphatidic acid receptor 1 (LPA1) mediated thrombospondin-1 (TSP1) regulation in astrocytes, which induce macrophage inflammatory protein 2(MIP2) secretion. MIP2 enhance PMN recruitment through CXC chemokine type 2 (CXCR2) activation. The purpose of this study was to investigate whether the LPA1-mediated inhibition of PMN recruitment and BBB protection after ICH is regulated by TSP1 and CXCR2 networks.MethodsICH induction was performed in CD1 mice using collagenase administration. AM966, a targeted LPA1 antagonist, was orally administered 1 and 12 h following ICH. further identify possible LPA1-mediated BBB protection mechanisms, we intracerebroventricularly (ICV) administered a CXCR2 ligand MIP2, as well as TSP1 CRISPR activation (ACT) with AM966. Consequently, we performed neurobehavioral, brain water content (BWC), Evans blue staining (EBS), immunofluorescence (IF), and western blot (WB) analyses.ResultsAfter ICH, astrocytes showed signs of LPA1, which peaked after 24 h, while PMN\\ displayed evidence of CXCR2. The AM966-mediated LPA1 suppression relieved PMN recruitment, diminished brain oedema, demonstrated extravasation (as evidenced by EBS), protected BBB integrity, and enhanced neurologic activity following ICH. AM966 treatment strongly reduced TSP1, CXCR2, Occludin, and Claudin-5 expressions and PMN recruitment following ICH, and their expressions were restored by MIP2 and TSP1 CRISPR (ACT).ConclusionsThis study shows that LAP1 suppression reduced PMN recruitment after ICH in mice via TSP1/CXCR2 signalling, which minimized BBB disruption and improved the CNS’s neurobehavioral functioning. Hence, LPA1 is a strong candidate for therapy to reduce PMN recruitment and offer protection of BBB integrity after ICH.

Association of first anti-seizure medication choice with injuries in older adults with newly diagnosed epilepsy

BackgroundEpilepsy incidence increases exponentially in older adults, who are also at higher risk of adverse drug effects. Anti-seizure medications (ASM) may be associated with sedation and injuries, but discontinuation can result in seizures. We sought to determine whether there was an association between prescribing non-guideline concordant ASM and subsequent injury as this could inform care models. MethodsRetrospective cohort study of adults 50 years or older with newly-diagnosed epilepsy in 2015–16, sampled from the MarketScan Databases. The outcome of interest was injury within 1-year of ASM prescription (e.g., burns, falls) and the exposure of interest was ASM category (recommended vs. not recommended by clinical guidelines). Descriptive statistics characterized covariates and a multivariable Cox-regression model was built to examine the association between ASM category and subsequent injury. Results5,931 people with newly diagnosed epilepsy were prescribed an ASM within 1-year. The three most common ASMs were: levetiracetam (62.86%), gabapentin (11.73%), and phenytoin (4.45%). Multivariable Cox-regression found that medication category was not associated with injury; however, older age (adjusted hazard ratio (AHR) 1.01/year), history of prior injury (AHR 1.77), traumatic brain injury (AHR 1.55) and ASM polypharmacy (AHR 1.32) were associated with increased hazard of injury. ConclusionsMost older adults appear to be getting appropriate first prescriptions for epilepsy. However, a substantial proportion still receives medication that guidelines suggest avoiding. In addition, we show that ASM polypharmacy is associated with an increased hazard of injury within 1- year. Efforts to improve prescribing in older adults with epilepsy should consider how to reduce. both polypharmacy and exposure to medications that guidelines recommend avoiding.

Fall incidence and associated factors in spinal cord injury patients who walk with or without an ambulatory assistive device

Background: The majority of ambulatory individuals with spinal cord injury (SCI) require an ambulatory assistive device (AAD). However, the association between falls and gait aid use is still inconsistent. Subgroup analysis may provide the opportunity to differentiate these factors more clearly. Objectives: This study aimed to explore fall incidence and associated factors in SCI patients who walk with or without an AAD. Materials and methods: Ninety-seven participants were interviewed for their baseline demographic data, physical activity, history of falling and fear of falling. They were divided into 2 groups, AAD and non AAD group. They were assessed with three functional tests, including the Timed Up and Go Test, Five Time Sit to Stand Test and 10 Meter Walk Test. Then fall data was followed for six months. Results: More than one-third of all participants experienced at least one fall (40%). The results also showed that the proportion of falls in the AAD group was slightly greater than that of the non-AAD group (AAD=46% and non-AAD=32%). In the AAD group, a multiple variable analysis indicated a significantly higher fall rate among those who were younger than 50 years, used a cane or crutches and had moderate to high physical activity. For the non-AAD group, it was found that poor balance and a history of falls were strong factors associated with more falls. Conclusion: Falls were a serious issue for the participants who walk with or without an ADD. However, the factors affecting falls in these two groups were different. Thus, therapists should consider the factors associated with falls for each group of SCI patients separately to provide proper rehabilitation that prevents falls and subsequent injury.

PO-03-042 A COOL DRINK OF WATER: CONVECTIVE ESOPHAGEAL COOLING PREVENTS THERMAL INJURY FROM RADIOFREQUENCY HEATING IN AN EX VIVO SWINE ESOPHAGUS MODEL

Esophageal heating and subsequent thermal injury are concerning adverse effects of radiofrequency (RF) energy ablation on the posterior wall of the left atrium. Active intraluminal esophageal cooling may provide thermal protection, allowing for effective delivery of RF energy to overlying myocardium without collateral damage to the underlying esophagus. To evaluate the impact of esophageal luminal cooling with a closed loop continuous flow irrigation on esophageal heating and thermal injury using an ex vivo model. A flexible tube was placed through the lumen of a swine esophagus and connected to a closed loop circuit consisting of a pump and water bath (Figure 1, panel A). The esophagus was submerged in a saline bath with a temperature of 36 °C and an impedance of 140 ohms. Ten non-contiguous RF lesions were delivered at 50 watts for 8 seconds directly on the outer esophageal wall with 4 mm irrigated RF ablation catheter. This was performed without irrigation (control), irrigation at 1.5 L/min with room temperature water (20 °C), and irrigation at 1.5 L/min with ice water (0 °C). Esophageal tissue samples were obtained from immunohistochemistry and the esophagus was cross sectioned and lesions were measured with digital calipers. Closed loop continuous flow esophageal irrigation with ice water yielded esophageal lesions with the smallest surface area (Figure 1, panel A), depth, and volume (Figure 1, panel B). Continuous esophageal irrigation with room temperature water resulted in the second smallest lesions. RF lesions without esophageal irrigation resulted in the largest and deepest lesion, as well as evidence of luminal esophageal injury (Figure 1, panel C & D). Histology showed preserved smooth muscle, glands, basement membrane and epithelium with cooled esophagus and transmural lesions with non-irrigated esophagus (Figure 1, panel C & D). Continuous endoluminal esophageal cooling reduced lesion size with RF energy delivery. There was no luminal injury with room temperature and ice water esophageal irrigation. Thus, both may be useful in prevention of endoluminal esophageal injury during poster wall RF ablation.

The effects of elongation strain on choroid plexus endothelial cells as a model of mild traumatic brain injury

Traumatic Brain Injuries (TBIs) account for a significant portion of morbidity and mortality accounting for approximately 2.5 million reported cases per year. However, there has been little research regarding the blood-cerebrospinal fluid barrier (BCSFB), the choroid plexus, in TBI pathophysiology. Choroid plexus endothelial cells (CPECs) play a critical role in maintaining CSF homeostasis and regulating neuroinflammation. These endothelial cells, once exposed to the shearing force associated with TBI, release proinflammatory cytokines and become leaky via the breakdown of gap junctions leading to an influx of immune cells. Identifying key cytokines involved in this process and critical timepoints post-injury will allow researchers to better understand key TBI pathophysiology. The aim of this study was to elucidate the cytokine response of CPECs post-mild shearing strain to mimic mild TBI (mTBI). We hypothesized that pro-inflammatory cytokines like IL-6 &amp; TNFα would be elevated post mTBI. Using primary human choroid plexus endothelial cells (HCPECs) purchased from ScienCell (Cat# 1300) and the FlexCell Tension system, HCPECs were subjected to a 12% mild mechanical strain (“one hit”), supernatant was collected, and 36 different cytokines and chemokines were measured at multiple time points post-injury using a membrane-based array (R&amp;D Systems, Cat# ARY005B). This was repeated in a “two hit” model where the cells were subjected to a second 12% strain, 24 hours after the first to examine two subsequent mild head injuries. The multiple time points of supernatant collection allowed for longitudinal measurement of cell behavior and cytokine profiles. Experimental controls included HCPECs plated on the FlexCell flexible membrane 6-well plates without being subjected to mechanical strain. Consistent with the literature and clinical TBI presentation, cytokines were elevated 48-hours post-injury. There were changes in cytokine production between 24- to 48- hours post-injury, most notably CCL2, MIP1α/MIP1β, G-CSF, IL-10 and CCL5 (RANTES), to name a few. Interestingly, while some cytokines increased after injury, such as the 2-fold and 4-fold increase in CCL2 between 24- and 48-hours post one and two hit, respectively, others decreased. There was a 3-fold decrease in RANTES between 24- and 48- hours post one hit, and a 2-fold decrease in G-CSF. Contrary to our hypothesis, cytokine responses post-injury were related to regulatory and anti-inflammatory responses as opposed to pro-inflammatory responses. As both RANTES and G-CSF are implicated in chronic inflammation, the results indicate that there was a decrease in pro-inflammatory responses in favor of more regulatory and anti-inflammatory responses post mTBI. Overall, this pilot project helped identify key cytokines involved in HCPEC signaling after mild mechanical strain and demonstrated a critical window between 24- and 48- hours post-injury for the treatment of mTBI. Indiana Academy of Sciences; Marian University This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Demographic Factors and Instantaneous Lower Extremity Injury Occurrence in a National Collegiate Athletic Association Division I Population.

Temporal prediction of the lower extremity (LE) injury risk will benefit clinicians by allowing them to better leverage limited resources and target those athletes most at risk. To characterize the instantaneous risk of LE injury by demographic factors of sex, sport, body mass index (BMI), and injury history. Descriptive epidemiologic study. National Collegiate Athletic Association Division I athletic program. A total of 278 National Collegiate Athletic Association Division I varsity student-athletes (119 males, 159 females; age = 19.07 ± 1.21 years, height = 175.48 ± 11.06 cm, mass = 72.24 ± 12.87 kg). Injuries to the LE were tracked for 237 ± 235 consecutive days. Sex-stratified univariate Cox regression models were used to investigate the association between time to first LE injury and sport, BMI, and LE injury history. The instantaneous LE injury risk was defined as the injury risk at any given point in time after the baseline measurement. Relative risk ratios and Kaplan-Meier curves were generated. Variables identified in the univariate analysis were included in a multivariate Cox regression model. Female athletes displayed similar instantaneous LE injury risk to male athletes (hazard ratio [HR] = 1.29; 95% CI= 0.91, 1.83; P = .16). Overweight athletes (BMI >25 kg/m2) had similar instantaneous LE injury risk compared with athletes with a BMI of <25 kg/m2 (HR = 1.23; 95% CI = 0.84, 1.82; P = .29). Athletes with previous LE injuries were not more likely to sustain subsequent LE injury than athletes with no previous injury (HR = 1.09; 95% CI = 0.76, 1.54; P = .64). Basketball (HR = 3.12; 95% CI = 1.51, 6.44; P = .002) and soccer (HR = 2.78; 95% CI = 1.46, 5.31; P = .002) athletes had a higher risk of LE injury than cross-country athletes. In the multivariate model, instantaneous LE injury risk was greater in female than in male athletes (HR = 1.55; 95% CI = 1.00, 2.39; P = .05), and it was greater in male athletes with a BMI of >25 kg/m2 than that in all other athletes (HR = 0.44; 95% CI = 0.19, 1.00; P = .05), but these findings were not significantly different. In a collegiate athlete population, previous LE injury was not a contributor to the risk of future LE injury, whereas being female or being male with a BMI of >25 kg/m2 resulted in an increased risk of LE injury. Clinicians can use these data to extrapolate the LE injury risk occurrence to specific populations.

The fetal response to maternal inflammation is dependent upon maternal IL-6 in a murine model

BackgroundThe induction of maternal inflammation in mice leads to fetal injury that is believed to be IL-6 dependent. The fetal inflammatory response, defined by elevated fetal or amniotic fluid IL-6, has been described as a potential mechanism for subsequent fetal injury. The role of maternal IL-6 production and signaling in the fetal IL-6 response is currently unclear. MethodsGenetic and anti-IL-6 antibody strategies were used to systematically block the maternal IL-6 response during inflammation. Chorioamnionitis was induced using intraperitoneal injection of lipopolysaccharide (LPS) at mid gestation (E14.5) and late gestation (E18.5). This model was used in pregnant C57Bl/6 dams, IL6-/- dams, C57Bl/6 dams treated with anti-IL-6 (blocks both classical and trans-signaling) or anti-gp130 antibodies (blocks trans-signaling only) and IL6+/− dams. Six hours following LPS injection, maternal serum, placental tissue, amniotic fluid and fetal tissue or serum were collected. A bead-based multiplex assay was used to evaluate levels of IL-6, KC, IL-1β, TNF, IL-10, IL-22, IFN-γ, IL-13 and IL-17A. ResultsChorioamnionitis in C57Bl/6 dams was characterized by elevated maternal serum levels of IL-6, KC and IL-22 with litter loss during mid gestation. The fetal response to maternal inflammation in C57Bl/6 mice was primarily characterized by elevated levels of IL-6, KC and IL-22 in the placenta, amniotic fluid and fetus during both mid and late gestation. A global IL-6 knockout (IL6-/-) eradicated the maternal, placental, amniotic fluid and fetal IL-6 response to LPS during mid and late gestation and improved litter survival, while minimally influencing the KC or IL-22 responses. Blocking maternal classical IL-6 signaling in C57Bl/6 dams at the time of LPS exposure diminished the maternal, placental, amniotic fluid and fetal IL-6 response during mid and late gestation, while blocking maternal IL-6 trans-signaling only affected fetal IL-6 expression. To evaluate whether maternal IL-6 was crossing the placenta and reaching the fetus, IL-6+/− dams were utilized in the chorioamnionitis model. IL-6+/− dams mounted a systemic inflammatory response following injection with LPS, characterized by elevated IL-6, KC and IL-22. IL-6-/- pups born to IL6+/− dams had decreased amniotic fluid levels of IL-6 and undetectable levels of fetal IL-6 compared to IL-6+/+ littermate controls. ConclusionThe fetal response to systemic maternal inflammation is dependent upon maternal IL-6 signaling, but maternal IL-6 is not crossing the placenta and reaching the fetus at detectable levels.

Change In Fall Risk-Increasing Drug Use Among Individuals with Parkinson Disease Before and After a Serious Injury (P2-5.032)

<h3>Objective:</h3> To describe fall risk-increasing drug (FRID) use before and after an unintentional traumatic injury or fall-related fracture and examine the extent to which hospital encounters affect medication prescribing in individuals with Parkinson disease (PD). <h3>Background:</h3> Individuals with PD are at increased risk of falls and fractures. FRIDs represent a major modifiable factor that can potentially reduce the risk of subsequent events. <h3>Design/Methods:</h3> We identified persons with PD hospitalized for injury or fracture and matched each person to up to 4 individuals with PD who were hospitalized for other reasons using 2013–2017 U.S. Medicare data. A difference-in-difference design was used to compare FRID dispensing before and after hospitalization between the two groups. We examined the changes in standardized daily doses of FRIDs in the two groups upon hospital admission and at 3-, 6-, and 12-months post-discharge, adjusting for covariates. Exploratory analyses were performed to evaluate potential medication discontinuation and tapering following discharge. <h3>Results:</h3> We identified 9,437 persons with PD who had a qualifying hospitalization for injury or fracture and 32,487 matched individuals. While both groups experienced reductions in standardized daily doses of FRIDs, the differences in dose reductions were minimal (−1.94, 95% CI [−2.05, −1.82] in the injury group vs. −1.91, 95% CI [−1.97, −1.84] in the non-injury group; p=0.66 at 12 months). Over 40% of subjects discontinued FRIDs at 3 months in both groups, and ~2/3 to 3/4 of these sustained discontinuations through one year. <h3>Conclusions:</h3> There were no clinically significant differences in FRID dose reductions pre- to post-hospitalization between PD individuals with injury or fracture versus those without. More efforts are needed to enhance deprescribing practices during transition of care, especially after a sentinel event, to prevent subsequent unintentional injuries or fractures. <b>Disclosure:</b> The institution of Dr. Pham Nguyen has received research support from National Institute of Health. The institution of Dr. Pham Nguyen has received research support from National Institute of Health. Dr. Gray has nothing to disclose. Mr. Newcomb has nothing to disclose. Miss Liu has nothing to disclose. The institution of Dr. Hamedani has received research support from Michael J. Fox Foundation. The institution of Dr. Hamedani has received research support from NIH. The institution of Dr. Hamedani has received research support from Biogen. The institution of Dr. Hamedani has received research support from Biohaven. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intercept Pharmaceuticals. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medullary Thyroid Cancer Consortium. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Provention Bio, Inc. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bluebird bio, Inc. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx Pharmaceuticals. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen Bioscence Inc.. The institution of Dr. Hennessy has received research support from US Food and Drug Administration. The institution of Dr. Hennessy has received research support from US National Institutes of Health. The institution of Dr. Hennessy has received research support from US Centers for Disease Control and Prevention. Dr. Wright Willis has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Pharmacoepidemiology and Drug Safety. The institution of Dr. Wright Willis has received research support from NIH. The institution of Dr. Wright Willis has received research support from NIA. The institution of Dr. Wright Willis has received research support from Biogen. The institution of Dr. Wright Willis has received research support from Parkinson Foundation. The institution of Dr. Wright Willis has received research support from Arcadia.

Chlorogenic acid induces endoplasmic reticulum stress in Botrytis cinerea and inhibits gray mold on strawberry

Chlorogenic acid (CGA) is a plant-derived compound with antifungal activity. However, the antifungal mechanism of CGA remains not fully revealed. The antifungal effect of CGA against Botrytis cinerea was assessed in the present study, and its mode of action was studied. Results demonstrated that CGA suppressed the growth of B. cinerea, as well as the development of gray mold (B. cinerea) on strawberry. Further analysis indicated that CGA induced endoplasmic reticulum (ER) stress in hyphae of B. cinerea resulting in an efflux of calcium (Ca2+) from the ER to the cytoplasm and then into mitochondria. The Ca2+ overload in mitochondria elicited the Ca2+-calmodulin-calcineurin cascade, resulting in a superoxide burst in the mitochondria. Finally, a decrease in ATP content and cell viability was observed in B. cinerea. This is the first report showing that the inhibitory effect of CGA towards B. cinerea involves an ER stress, followed by a Ca2+ release from the ER to the mitochondria, resulting in a superoxide burst and subsequent oxidative injury that reduces cell viability. Thus, CGA can be considered as an effectively substance to control gray mold on strawberry.