Neuroendocrine Disruptions Following Head Injury.

PURPOSE OF REVIEW: This article reviews hypopituitarism after TBI, the importance of pituitary hormones, and related controversies, concluding with a suggested patient approach. RECENT FINDINGS: While earlier studies focused on increased pituitary deficiencies after moderate-severe TBI, recent studies have focused on deficiencies after mild TBI. There has been increasing focus on the role of growth hormone after injury; growth hormone is the most frequent reported deficiency at 1 year post-TBI, and an area with unresolved questions. While more research is needed to quantify the risk of deficiencies in special populations, and establish the natural history, increasing data indicate an increase in hypopituitarism after other acquired brain injuries; the potential role of pituitary hormone deficiencies after stroke and after COVID-19 infection is an area of active inquiry. Given the negative health effects of untreated hypopituitarism and the opportunity to intervene via hormone replacement, it is important to recognize the role of pituitary hormone deficiencies after TBI.

Stakeholder Perspectives on the School Experiences of Students With Traumatic Brain Injury: The Effects of COVID-19 Pandemic on Service Delivery.

BACKGROUND: For students with traumatic brain injury (TBI), the COVID-19 pandemic exacerbated challenges they were already experiencing at school. METHODS: This qualitative study employed focus groups and interviews with students, parents, school, and medical personnel to explore the school experiences of students with TBI. Thematic qualitative analyses were used. RESULTS: Key themes from the analysis include (a) incidence of brain injuries decreased; (b) screen time for students with TBI exacerbated symptoms; (c) COVID protocols at school made it difficult for educators to identify and provide accommodations for students with TBI; (d) COVID protocols at school could inadvertently exacerbate mental health difficulties after a TBI; and (e) COVID-related logistics increased the time between an injury and return to school or return to play. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: The results from this study suggest that professional development for teachers supporting students with TBI is needed, especially for online learning environments. Additionally, because mental/behavioral health concerns may arise for students with TBI in online learning environments, school health care providers can work with families to assess a student's mental health, making referrals to appropriate supports. CONCLUSIONS: There is a significant need for professional development and school-wide infrastructure supportive of students with TBI.

Pediatric all-terrain vehicle (ATV) related head injury rates and patterns: A 10-year nationwide analysis.

INTRODUCTION: The use of all-terrain vehicles (ATVs) carries significant risk of permanent injury and death, disproportionately affecting children. These injuries commonly affect the head and are especially severe among children as they are often unhelmeted and more likely than adults to experience rollover injuries. Many studies examining patients with ATV-related injuries are single-center cohort studies, with few focusing specifically on head injuries. In the present study, we aimed to characterize the annual incidence of ATV-related head injuries between 2012 and 2021, classify and compare head injury types, and identify descriptive characteristics of ATV-related head injury victims. METHODS: Using the US Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) database, we queried all head injuries associated with operating or riding an ATV in children under 18 years-old from over 100 emergency departments (EDs). Patient information regarding age, race, sex, location of incident, diagnoses, and sequelae were analyzed. We also collected the estimated number of ATV-related head injuries from all US EDs using the NEISS algorithm provided by the database. RESULTS: Using the NEISS algorithm we identified 67,957 (95% CI: 43,608 - 92,305) total pediatric ATV-related head injuries between 2012 and 2021. The annual incidence of ATV-related head injury was similar throughout this study period except for a 20% increase during the COVID-19 pandemic period of 2019-2021 (2019: 6382 injuries, 2020: 6757 injuries, 2021: 7600 injuries). A subset of 1890 cases from approximately 100 EDs were then analyzed. Unspecified closed head injuries were the prevailing type of injury (38%, 900/1890), followed by concussions (27%, 510/1890). More severe injuries included intracranial hemorrhages in 91 children (3.8%, 91/1890). Injuries of all types were predominantly seen in 14-17 year-old's (780/1890, 41%) and in males (64.1%, 1211/1890). In addition, ATV-associated injuries were significantly more common in those coded as white (58.0%, 1096/1890) than any other racial group. ATV-associated accidents among children younger than 9 more commonly occurred at the home compared to accidents involving children older than 9 (57% vs. 32%, p < 0.0001). CONCLUSION: ATV-related head injuries cause a significant annual burden among children, with growing incidence in recent years. Further research may wish to explore potential benefits of helmet use and supervision of younger children in possible prevention of these accidents and their associated economic and non-economic costs.

Changes in patterns of traumatic brain injury in the Michigan Trauma Quality Improvement Program database early in the COVID-19 pandemic.

OBJECTIVE: The authors' objective was to investigate the impact of the global COVID-19 pandemic on hospital presentation and process of care for the treatment of traumatic brain injuries (TBIs). Improved understanding of these effects will inform sociopolitical and hospital policies in response to future pandemics. METHODS: The Michigan Trauma Quality Improvement Program (MTQIP) database, which contains data from 36 level I and II trauma centers in Michigan and Minnesota, was queried to identify patients who sustained TBI on the basis of head/neck Abbreviated Injury Scale (AIS) codes during the periods of March 13 through July 2 of 2017-2019 (pre-COVID-19 period) and March 13, 2020, through July 2, 2020 (COVID-19 period). Analyses were performed to detect differences in incidence, patient characteristics, injury severity, and outcomes. RESULTS: There was an 18% decrease in the rate of encounters with TBI in the first 8 weeks (March 13 through May 7), followed by a 16% increase during the last 8 weeks (May 8 through July 2), of our COVID-19 period compared with the pre-COVID-19 period. Cumulatively, there was no difference in the rates of encounters with TBI between the COVID-19 and pre-COVID-19 periods. Severity of TBI, as measured with maximum AIS score for the head/neck region and Glasgow Coma Scale score, was also similar between periods. During the COVID-19 period, a greater proportion of patients with TBI presented more than a day after sustaining their injuries (p = 0.046). COVID-19 was also associated with a doubling in the decubitus ulcer rate from 1.0% to 2.1% (p = 0.002) and change in the distribution of discharge status (p = 0.01). Multivariable analysis showed no differences in odds of death/hospice discharge, intensive care unit stay of at least a day, or need for a ventilator for at least a day between the COVID-19 and pre-COVID-19 periods. CONCLUSIONS: During the early months of the COVID-19 pandemic, the number of patients who presented with TBI was initially lower than in the years 2017-2019 prior to the pandemic. However, there was a subsequent increase in the rate of encounters with TBI, resulting in overall similar rates of TBI between March 13 through July 2 during the COVID-19 period and during the pre-COVID-19 period. The COVID-19 cohort was also associated with negative impacts on time to presentation, rate of decubitus ulcers, and discharge with supervision. Policies in response to future pandemics must consider the resources necessary to care for patients with TBI.

The Pediatric Guideline Adherence and Outcomes (PEGASUS Argentina) program in severe traumatic brain injury: study protocol adaptations during the COVID-19 pandemic for a multisite implementation-effectiveness cluster randomized controlled trial.

BACKGROUND: The aim of this protocol is to describe the study protocol changes made and subsequently implemented to the Pediatric Guideline Adherence and Outcomes (PEGASUS) Argentina randomized controlled trial (RCT) for care of children with severe traumatic brain injuries (TBI) imposed by the COVID-19 pandemic. The PEGASUS study group met in spring 2020 to evaluate available literature review guidance and the study design change or pausing options due to the potential interruption of research. METHODS: As a parallel cluster RCT, pediatric patients with severe TBIs are admitted to 8 control (usual care) and 8 intervention (PEGASUS program) hospitals in Argentina, Chile, and Paraguay. PEGASUS is an intervention that aims to increase guideline adherence and best practice care for improving patient outcomes using multi-level implementation science-based approaches. Strengths and weaknesses of proposed options were assessed and resulted in a decision to revert from a stepped wedge to a parallel cluster RCT but to not delay planned implementation. DISCUSSION: The parallel cluster design was considered more robust and flexible to secular interruptions and acceptable and feasible to the local study sites in this situation. Due to the early stage of the study, the team had flexibility to redesign and implement a design more compatible with the conditions of the research landscape in 2020 while balancing analytical methods and power, logistical and implementation feasibility, and acceptability. As of fall 2022, the PEGASUS RCT has been active for nearly 2 years of implementation and data collection, scheduled to be completed in in fall 2023. The experience of navigating research during this period will influence decisions about future research design, strategies, and contingencies. TRIAL REGISTRATION: Pediatric Guideline Adherence and Outcomes-Argentina. Registered with ClinicalTrials.gov Identifier NCT03896789 on April 1, 2019.

Post-9/11 veterans perceptions of the pandemic: Areas of greatest impact on health and well-being.

Objective: Assess potential impacts of the COVID-19 pandemic on a subset of Post-9/11 U.S. Veterans included in a study of post-traumatic epilepsy (PTE). Methods: Two measures were added to a structured health interview for Veterans during temporary pandemic research shutdown: a validated health questionnaire [1] previously completed by survey, and a semi-structured instrument developed to assess whether pandemic conditions affected responses to the health questionnaire and identify unique impacts. Interviews were conducted between August 2020 - February 2021. Scaled items were calculated and t-tests used to compare results. Open-ended items were coded using thematic analyses. Results: Veterans identified eight major areas of impact with negative and positive impacts: mental health, family, social, work/employment, access to resources, physical health, finances, and education. Innovation: The temporary shut-down of a large health study for Post-9/11 Veterans provided an opportunity to devise an instrument to assess COVID-19's impact on health and well-being. The instrument was accepted as of the first Veteran instrument in a pandemic SDOH research repository [2], and is being used in other studies. Conclusion: This study highlights the need to assess and understand interrelated relationships of factors impacting health and well-being, especially as COVID-19 moves from pandemic to endemic with reverberating effects across multiple social determinants of health (SDOH).

Therapeutic Potential of Human Immature Dental Pulp Stem Cells Observed in Mouse Model for Acquired Aplastic Anemia.

Aplastic anemia (AA) is a rare and serious disorder of hematopoietic stem cells (HSCs) that results in the loss of blood cells due to the failure of the bone marrow (BM). Although BM transplantation is used to treat AA, its use is limited by donor availability. In this sense, mesenchymal stem cells (MSCs) can offer a novel therapeutic approach for AA. This is because the MSCs contribute to the hematopoietic niche organization through their repopulating. In our study, we used the human immature dental pulp stem cell (hIDPSC), an MSC-like cell, to explore an alternative therapeutic approach for AA. For this, isogenic C57BL/6 mice were exposed to total body irradiation (TBI) to induce the AA. After 48 h of TBI, the mice were intraperitoneally treated with hIDPSC. The immunohistochemistry analyses confirmed that the hIDPSCs migrated and grafted in the mouse bone marrow (BM) and spleen, providing rapid support to hematopoiesis recovery compared to the group exposed to radiation, but not to those treated with the cells as well as the hematological parameters. Six months after the last hIDPSC transplantation, the BM showed long-term stable hematopoiesis. Our data highlight the therapeutic plasticity and hematoprotective role of hIDPSC for AA and potentially for other hematopoietic failures.

Intraparenchymal fiberoptic intracranial pressure monitoring and decompressive craniectomy in meningioma case with critical intracranial pressure: A case report during COVID-19 pandemic.

Introduction: Meningioma is a slow-growing tumor that can cause neurological emergency due to intracranial hypertension. The definitive therapy is indeed emergency resection, but it is not always possible in several countries due to limited capacity and/or capability of the emergency operating room. The use of intraparenchymal fiberoptic intracranial pressure (ICP) monitoring and decompressive craniectomy (DC) in cases of brain tumors might be possible, but it is uncommon. We report a meningioma patient in whom immediate meningioma resection was considered too risky due to intensive care unit (ICU) shortage during COVID-19 pandemic and, therefore, underwent these procedures as life-saving measures. Case presentation: A 24-year-old man was brought to the emergency room with a chief complaint of seizure. Physical examination was notable for decreased consciousness (Glasgow Coma Scale (GCS) 11) and a dilated left pupil with intact light reflex. A contrasted Brain CT Scan revealed extra-axial mass on the left sphenoid with extensive tentacle edema, which pushed the midline structures 2 cm toward the contralateral side. Discussion: The patient was diagnosed with Left Sphenoid Meningioma. We decided to perform intraparenchymal fiberoptic ICP monitor insertion and DC considering the situation, device availability, safety, and efficacy. The patient slowly regained consciousness in the recovery room after the procedure. The best-observed GCS was 12. Two weeks afterward, the patient came back to our outpatient clinic neurologically intact. The patient was then planned for elective tumor resection. Conclusion: ICP monitoring and DC are not commonly performed on brain tumor cases. However, in suboptimal situations, these procedures might save lives. The present case showed that ICP monitor and DC were helpful in times of ICU shortage.

The endothelial glycocalyx in critical illness: A pediatric perspective.

The vascular endothelium is the interface between circulating blood and end organs and thus has a critical role in preserving organ function. The endothelium is lined by a glycan-rich glycocalyx that uniquely contributes to endothelial function through its regulation of leukocyte and platelet interactions with the vessel wall, vascular permeability, coagulation, and vasoreactivity. Degradation of the endothelial glycocalyx can thus promote vascular dysfunction, inflammation propagation, and organ injury. The endothelial glycocalyx and its role in vascular pathophysiology has gained increasing attention over the last decade. While studies characterizing vascular glycocalyx injury and its downstream consequences in a host of adult human diseases and in animal models has burgeoned, studies evaluating glycocalyx damage in pediatric diseases are relatively few. As children have unique physiology that differs from adults, significant knowledge gaps remain in our understanding of the causes and effects of endothelial glycocalyx disintegrity in pediatric critical illness. In this narrative literature overview, we offer a unique perspective on the role of the endothelial glycocalyx in pediatric critical illness, drawing from adult and preclinical data in addition to pediatric clinical experience to elucidate how marked derangement of the endothelial surface layer may contribute to aberrant vascular biology in children. By calling attention to this nascent field, we hope to increase research efforts to address important knowledge gaps in pediatric vascular biology that may inform the development of novel therapeutic strategies.

Role of Technology Business Incubator (TBI) in Sustaining Start-Ups: The Case of Startup Incubation and Business Innovation Lab (SIBIL)

This case study is about Startup Incubation and Business Innovation Lab (SIBIL), an incubation center working toward the implementation of startup policy in India. SIBIL provides support and guidance for the growth and business development of the new innovative start-ups located across India. It provides support for mobilizing seed funds, angel investors and firm spin-off apart from providing marketing expertise for commercialization of products and marketing research. This case has been written in the times when COVID-19 has brought various opportunities and threats to the start-ups and hence it is challenging for incubators to draw future action plans. The biggest challenge has been seen in terms of maintaining sustenance of start-ups. This case highlights two companies facing similar problems and draws future scenarios for them. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature.

BACKGROUND: The initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain controversial. Some studies suggest that moderate to severe TBI is sufficient to promote tau pathology; however, others suggest that it is simply a consequence of aging. We therefore conducted a systematic narrative review of the literature addressing whether a single moderate to severe head injury leads to long-term development of tauopathy in both humans and animal models. METHODS: Studies considered for inclusion in this review assessed a single moderate to severe TBI, assessed tau pathology at long-term timepoints post-injury, comprised experimental or observational studies, and were peer-reviewed and published in English. Databases searched included: PUBMED, NCBI-PMC, EMBASE, Web of Science, Academic Search Premiere, and APA Psychnet. Search results were uploaded to Covidence®, duplicates were removed, and articles underwent an abstract and full-text screening process. Data were then extracted and articles assessed for risk of bias. FINDINGS: Of 4,150 studies screened, 26 were eligible for inclusion, of which 17 were human studies, 8 were preclinical animal studies, and 1 included both human and preclinical animal studies. Most studies had low to moderate risk of bias. Most human and animal studies (n = 12 and 9, respectively) suggested that a single moderate to severe TBI resulted in greater development of long-term tauopathy compared to no history of head injury. This conclusion should be interpreted with caution, however, due to several limitations: small sample sizes; inconsistencies in controlling for confounding factors that may have affected tau pathology (e.g., family history of dementia or neurological illnesses, apolipoprotein E genotype, etc.), inclusion of mostly males, and variation in reporting injury parameters. INTERPRETATION: Results indicate that a single moderate to severe TBI leads to greater chronic development of tauopathy compared to no history of head injury. This implies that tau pathology induced may not be transient, but can progressively develop over time in both humans and animal models. Targeting these tau changes for therapeutic intervention should be further explored to elucidate if disease progression can be reversed or mitigated.

The Effect of Direct Oral Anti-Coagulants on Delayed Traumatic Intracranial Hemorrhage After Mild Traumatic Brain Injury: A Systematic Review.

BACKGROUND: The use of anticoagulant medications leads to a higher risk of developing traumatic intracranial hemorrhage (tICH) after a mild traumatic brain injury (mTBI). The management of anticoagulated patients can be difficult to determine when the initial head computed tomography is negative for tICH. There has been limited research on the risk of delayed tICH in patients taking direct oral anticoagulant (DOAC) medications. OBJECTIVE: Our aim was to determine the risk of delayed tICH for patients anticoagulated with DOACs after mTBI. METHODS: We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched several medical databases to examine the risk of delayed tICH in patients on DOACs. RESULTS: There were 1252 nonduplicate studies that were identified through an initial database search, 15 of which met our inclusion and exclusion criteria and were included in our analysis after full-text review. A total of 1375 subjects were combined among the 15 studies, with 20 instances of delayed tICH after mTBI. Nineteen of the 20 patients with a delayed tICH were discharged without any neurosurgical intervention, and 1 patient on apixaban died due to a delayed tICH. CONCLUSIONS: This systematic review confirms that delayed tICH after mTBI in patients on DOACs is uncommon. However, large, multicenter, prospective studies are needed to confirm the true incidence of clinically significant delayed tICH after DOAC use. Due to the limited data, we recommend using shared decision-making for patients who are candidates for discharge.

Performance validity testing via telehealth and failure rate in veterans with moderate-to-severe traumatic brain injury: A veterans affairs TBI model systems study.

BACKGROUND: The COVID-19 pandemic has led to increased utilization of teleneuropsychology (TeleNP) services. Unfortunately, investigations of performance validity tests (PVT) delivered via TeleNP are sparse. OBJECTIVE: The purpose of this study was to examine the specificity of the Reliable Digit Span (RDS) and 21-item test administered via telephone. METHOD: Participants were 51 veterans with moderate-to-severe traumatic brain injury (TBI). All participants completed the RDS and 21-item test in the context of a larger TeleNP battery. Specificity rates were examined across multiple cutoffs for both PVTs. RESULTS: Consistent with research employing traditional face-to-face neuropsychological evaluations, both PVTs maintained adequate specificity (i.e., > 90%) across previously established cutoffs. Specifically, defining performance invalidity as RDS < 7 or 21-item test forced choice total correct < 11 led to < 10%false positive classification errors. CONCLUSIONS: Findings add to the limited body of research examining and provide preliminary support for the use of the RDS and 21-item test in TeleNP via telephone. Both measures maintained adequate specificity in veterans with moderate-to-severe TBI. Future investigations including clinical or experimental "feigners" in a counter-balanced cross-over design (i.e., face-to-face vs. TeleNP) are recommended.

Examining the Emergency Medical Treatment and Active Labor Act: impact on telemedicine for neurotrauma.

The Emergency Medical Treatment and Active Labor Act (EMTALA) protects patient access to emergency medical treatment regardless of insurance or socioeconomic status. A significant result of the COVID-19 pandemic has been the rapid acceleration in the adoption of telemedicine services across many facets of healthcare. However, very little literature exists regarding the use of telemedicine in the context of EMTALA. This work aimed to evaluate the potential to expand the usage of telemedicine services for neurotrauma to reduce transfer rates, minimize movement of patients across borders, and alleviate the burden on tertiary care hospitals involved in the care of patients with COVID-19 during a global pandemic. In this paper, the authors outline EMTALA provisions, provide examples of EMTALA violations involving neurosurgical care, and propose guidelines for the creation of telemedicine protocols between referring and consulting institutions.