Factors Affecting Peripheral Intravenous Catheter Placement During Pediatric Trauma Resuscitation.

INTRODUCTION: Intravenous access is required for resuscitation of injured patients but may be delayed in children because of challenges associated with peripheral intravenous (PIV) catheter placement. Early identification of factors predisposing patients to difficult PIV placement can assist in deciding strategies for timely intravenous access. METHODS: We conducted a retrospective, video-based review of injured children and adolescents treated between April 2018 and May 2019. Patient demographic, physiological, injury, and resuscitation characteristics were obtained from the patient record, including age, race, weight, injury type, Injury Severity Score, initial systolic blood pressure, initial Glasgow Coma Score, intubation status, activation level, and presence of prearrival notification. Video review was used to determine the time to PIV placement, the number of attempts required, the purpose for additional access, and the reason for abandonment of PIV placement. Multivariable regressions were used to determine factors associated with successful placement. RESULTS: During the study period, 154 consented patients underwent attempts at PIV placement in the trauma bay. Placement was successful in 139 (90.3%) patients. Older patients (OR [odds ratio]: 0.9, 95% confidence interval [CI]: 0.9, 0.9) and patients who required the highest level activation response (OR: 0.0, 95% CI: 0.0, 0.3) were less likely to have an attempt at PIV placement abandoned. Children with nonblunt injuries (OR: 11.6, 95% CI: 1.3, 119.2) and pre-existing access (OR: 39.6, 95% CI: 7.0, 350.6) were more likely to have an attempt at PIV placement abandoned. Among patients with successful PIV placement, the time required for establishing PIV access was faster as age increased (-0.5 s, 95% CI: -1.1, -0.0). CONCLUSIONS: Younger age was associated with abandonment of PIV attempts and, when successful, increased time to placement. Strategies to improve successful PIV placement and alternate routes of access should be considered early to prevent treatment delays in younger children.

EasyTBSA as a method for calculating total body surface area burned: a validation study.

BACKGROUND: Current methods of burn estimation can lead to incorrect estimates of the total body surface area (TBSA) burned, especially among injured children. Inaccurate estimation of burn size can impact initial management, including unnecessary transfer to burn centres and fluid overload during resuscitation. To address these challenges, we developed a smartphone application (EasyTBSA) that calculates the TBSA of a burn using a body-part by body-part approach. The aims of this study were to assess the accuracy of the EasyTBSA application and compare its performance to three established methods of burn size estimation (Lund-Browder Chart, Rule of Nines and Rule of Palms). METHODS: Twenty-four healthcare providers used each method to estimate burn sizes on moulaged manikins. The manikins represented different ages (infant, child and adult) with different TBSA burns (small <20%, medium 20%-49% and large >49%). We calculated the accuracy of each method as the difference between the user-estimated and actual TBSA. The true value of the complete body surface area of the manikins was obtained by three-dimensional scans. We used multivariable modelling to control for manikin size and method. RESULTS: Among all age groups and burn sizes, the EasyTBSA application had the greatest accuracy for burn size estimation (-0.01%, SD 3.59%) followed by the Rule of Palms (3.92%, SD 10.71%), the Lund-Browder Chart (4.42%, SD 5.52%) and the Rule of Nines (5.05%, SD 6.87%). CONCLUSIONS: The EasyTBSA application may improve the estimation of TBSA compared with existing methods.

The impact of parental bariatric surgery and patient age on laparoscopic sleeve gastrectomy outcomes in adolescents.

BACKGROUND: Adolescent obesity is multifactorial, but parental history is the most significant risk factor. Laparoscopic sleeve gastrectomy (LSG) is part of the multidisciplinary approach to adolescent weight loss. OBJECTIVE: We aimed to evaluate the effects of parental history of bariatric surgery, as well as age at time of operation, on adolescents who underwent LSG at our institution. METHODS: We performed a retrospective review of patients, aged 10 to 19 years, who underwent LSG from January 2010 to December 2019. The adolescent bariatric surgical dataset maintained by our group was used to obtain patient demographics, weight, body mass index (BMI), and parental history of bariatric surgery. RESULTS: Among 328 patients, 76 (23.2%) had parents who had previously undergone bariatric surgery. These patients were significantly heavier by weight (p = 0.012) at the time of operation but had no difference in postoperative weight loss. When all patients were compared by age at operation (< 16 years, n = 102, ≥ 16 years, n = 226), there were few differences in outcomes. CONCLUSIONS: LSG is an effective approach to surgical weight loss in adolescents. Patient age should not be a barrier to weight loss surgery, especially among patients with a parental history of obesity. By intervening at a younger age, the metabolic sequelae of obesity may be reduced.

Assessment of Nonroutine Events During Intubation After Pediatric Trauma.

BACKGROUND: Intubation in the early postinjury phase can be a high-risk procedure associated with an increased risk of mortality when delayed. Nonroutine events (NREs) are workflow disruptions that can be latent safety threats in high-risk settings and may contribute to adverse outcomes. MATERIALS AND METHODS: We reviewed videos of intubations of injured children (age<17 y old) in the emergency department occurring between 2014 and 2018 to identify NREs occurring between the decision to intubate and successful intubation ("critical window"). RESULTS: Among 34 children requiring intubation, the indications included GCS≤8 (n = 20, 58.8%), cardiac arrest (n = 6, 17.6%), airway protection (n = 5, 14.7%), and respiratory failure (n = 3, 8.8%). The median duration of the "critical window" was 7.5 min (range 1.4-27.5 min), with a median of six NREs per case in this period (range 2-30). Most NREs (n = 159, 61.9%) delayed workflow, with 31 (12.1%) of these delays each lasting more than one minute. Eighty-seven NREs (33.9%) had a potential for harm but did not lead to direct patient harm. The most common NREs directly related to the intubation process were poor positioning for intubation (n = 23, 8.9%) and difficulty passing the endotracheal tube (n = 5, 1.9%), with most being attributed to the anesthesiologist performing the intubation (n = 51, range 0-7). CONCLUSIONS: Workflow disruptions related to nonroutine events were frequent during pediatric trauma intubation and were often associated with delays and potential for patient harm. Interventions for improving the efficiency and timeliness of the critical window should focus on adherence to intubation protocol and improving communication and teamwork related to tasks in this phase.

Personal Protective Equipment Adherence of Pediatric Resuscitation Team Members During the COVID-19 Pandemic.

STUDY OBJECTIVE: During the COVID-19 pandemic, health care workers have had the highest risk of infection among essential workers. Although personal protective equipment (PPE) use is associated with lower infection rates, appropriate use of PPE has been variable among health care workers, even in settings with COVID-19 patients. We aimed to evaluate the patterns of PPE adherence during emergency department resuscitations that included aerosol-generating procedures. METHODS: We conducted a retrospective, video-based review of pediatric resuscitations involving one or more aerosol-generating procedures during the first 3 months of the COVID-19 pandemic in the United States (March to June 2020). Recommended adherence (complete, inadequate, absent) with 5 PPE items (headwear, eyewear, masks, gowns, gloves) and the duration of potential exposure were evaluated for individuals in the room after aerosol-generating procedure initiation. RESULTS: Among the 345 health care workers observed during 19 resuscitations, 306 (88.7%) were nonadherent (inadequate or absent adherence) with the recommended use of at least 1 PPE type at some time during the resuscitation, 23 (6.7%) of whom had no PPE. One hundred and forty health care workers (40.6%) altered or removed at least 1 type of PPE during the event. The aggregate time in the resuscitation room for health care workers across all events was 118.7 hours. During this time, providers had either absent or inadequate eyewear for 46.4 hours (39.1%) and absent or inadequate masks for 35.2 hours (29.7%). CONCLUSION: Full adherence with recommended PPE use was limited in a setting at increased risk for SARS-CoV-2 virus aerosolization. In addition to ensuring appropriate donning, approaches are needed for ensuring ongoing adherence with PPE recommendations during exposure.

Patterns of paediatric massive blood transfusion protocol use in trauma and non-trauma patients.

BACKGROUND: Massive blood transfusion is infrequently required by children but can be a lifesaving intervention for haemorrhage or coagulopathy. Product volumes and ratios administered during the initiation of paediatric massive blood transfusion protocol (MBTP) are highly variable and the optimal component ratio is unknown. METHODS/MATERIALS: We performed a single-centre retrospective chart review of patients (<20 years) who received MBTP activation from August 2012 through January 2018. Logistic regression was used to determine the association between MBTP use characteristics (including blood product type and volume transfused, extracorporeal membrane oxygenation [ECMO] support, and cardiac arrest occurrence) and 24-h mortality. "Low" product ratio was defined as a ratio of plasma or platelets to red blood cells (RBCs) of <1:2 and "high" as ≥1:2. RESULTS: Ninety-eight MBTPs were activated for 89 patients (range 1-4 per patient). The most common underlying diagnoses were congenital heart disease (CHD, n = 28, 31.5%), followed by cardiopulmonary disease, and trauma. CHD patients required the greatest volume of RBCs (226.3 ml/kg, 95%CI [160.0, 292.7], p = 0.002) and platelets (46.7 ml/kg, 95%CI [33.2, 60.2], p < 0.001). A "low" product ratio was more common for the MBTP, with its incidence similar among the underlying diagnoses. CONCLUSION: An MBTP developed for trauma patients can be applied to non-trauma patients but standard MBTP components may not be optimal for all children. These findings show that underlying patient diagnoses may be a factor when designing an MBTP for a heterogeneous paediatric population.

Variations in the management of adolescent adnexal torsion at a single institution and the creation of a unified care pathway.

PURPOSE: Adnexal torsion is a gynecologic emergency, requiring intervention for tissue preservation. At our institution, torsion is managed by pediatric surgeons or gynecologists. We evaluated differences between specialties to streamline evaluation for children with gynecological emergencies, develop a clinical pathway, and prevent care delays. METHODS: A retrospective review of adolescents undergoing intervention for adnexal torsion from 2004-2018 was performed. Differences in time to intervention, operation duration, the procedure performed, and length of stay (LOS) between the specialties were analyzed. RESULTS: Eighty-six patients underwent 94 operations for presumed adnexal torsion with 87 positive cases. Pediatric surgeons performed 60 operations and 34 cases were performed by gynecologists. Preservation of fertility was the goal in both cohorts and the rate of oophoropexy, cystectomy, and oophorectomy were similar between the cohorts (p = 0.14, p = 1.0, p = 0.39, respectively). There was no difference in intra-operative time (p = 0.69). LOS was shorter in the gynecology cohort (median 1 day [1-2] vs. 2 days [2-3], p > 0.001). CONCLUSIONS: Adnexal torsion is a time-sensitive diagnosis requiring prompt intervention for ovarian or fallopian tube preservation. A multidisciplinary institutional care pathway should be developed and implemented.

Assessment of the Need for Immediate Trauma Team Presence for Infants Presenting in Cardiac Arrest.

OBJECTIVES: Out-of-hospital cardiac arrest (OHCA) is rare in infants, with the cause of arrest often unknown upon presentation. Nonaccidental trauma is a potential etiology of OHCA among infants, but its occult presentation makes this etiology challenging to diagnose. In the absence of apparent injuries, identifying the need for trauma team activation is difficult during the initial resuscitation of infants with OHCA. METHODS: We performed a retrospective chart review of infants younger than 1 year old who presented to Children's National Health System from 2012 to 2016 with cardiopulmonary resuscitation in progress. Medical records and the trauma registry were reviewed for relevant resuscitation information. Autopsy records provided the cause and manner of death, contributing factors to death, and evidence of injury. RESULTS: Among 592 infants undergoing resuscitation during the study period, 34 infants (5.7%) presented in cardiac arrest. The average age on presentation was 101.2 days (standard deviation 78.7). Most of the patients (n = 32, 94.1%) died in the emergency department, with none surviving to discharge. Among the 32 infants for whom autopsy records were available, the cause of death was nonaccidental trauma in one patient (3.1%). CONCLUSIONS: Infant OHCA had poor outcomes, with trauma as a rare etiology. In the absence of external signs of injury or known injury mechanism, immediate trauma team presence was not beneficial for these infants during the initial resuscitation phase.

The Development and Implementation of a Transfer Follow-up Program at a Level I Pediatric Trauma Center.

BACKGROUND: Inconsistent trauma patient referral feedback limits trauma system growth and may perpetuate suboptimal care. Trauma and burn patients are transferred to our Level I pediatric trauma center from hospitals in the surrounding metropolitan area. In the past, we had no consistent method to address performance improvement opportunities or provide information on patient outcomes to the referring facilities. The purpose of this study is to describe the implementation and evaluation of a formal electronic transfer follow-up program. METHODS: This was a before-and-after quality improvement study of pediatric trauma patients comparing prefeedback program implementation (2018) to postfeedback program implementation (2019). A new transfer patient feedback program was designed to address low rates of feedback provided to referring hospitals. Our center worked with a software developer to create a program that stored outside hospital contacts, automated follow-up letters, and tracked the number of letters sent, and opened, to enhance communication between trauma center and referring facilities. RESULTS: A total of 383 preprogram (2018) patients and 369 postprogram (2019) patients were evaluated. Since program implementation, an average of 70% follow-up per referral and an average return rate of 45% have been maintained. CONCLUSION: As we continue to use the system and make changes, we fully expect to exceed our goal in providing essential feedback on the care of pediatric trauma and burn patients to our referring facilities.

Prevalence and Outcomes of High versus Low Ratio Plasma to Red Blood Cell Resuscitation in a Multi-Institutional Cohort of Severely Injured Children.

BACKGROUND: The benefit of targeting high ratio fresh frozen plasma (FFP):red blood cell (RBC) transfusion in pediatric trauma resuscitation is unclear as existing studies are limited to patients who retrospectively met criteria for massive transfusion. The purpose of this study is to evaluate the use of high ratio FFP:RBC transfusion and the association with outcomes in children presenting in shock. METHODS: A post-hoc analysis of a 24-institution prospective observational study (4/2018-9/2019) of injured children <18 years with elevated age-adjusted shock index was performed. Patients transfused within 24 hours were stratified into cohorts of low (<1:2) or high (>1:2) ratio FFP:RBC. Nonparametric Kruskal-Wallis and chi-square were used to compare characteristics and mortality. Competing risks analysis was used to compare extended (≥75th percentile) ventilator, intensive care, and hospital days while accounting for early deaths. RESULTS: Of 135 children with median (IQR) age 10 (5,14) years and weight 40 (20,64) kg, 85 (63%) received low ratio transfusion and 50 (37%) high ratio despite similar activation of institutional massive transfusion protocols (MTP; low-38%, high-46%, p = .34). Most patients sustained blunt injuries (70%). Median injury severity score was greater in high ratio patients (low-25, high-33, p = .01); however, hospital mortality was similar (low-24%, high-20%, p = .65) as was the risk of extended ventilator, ICU, and hospital days (all p > .05). CONCLUSION: Despite increased injury severity, patients who received a high ratio of FFP:RBC had comparable rates of mortality. These data suggest high ratio FFP:RBC resuscitation is not associated with worst outcomes in children who present in shock. MTP activation was not associated with receipt of high ratio transfusion, suggesting variability in MTP between centers. LEVEL OF EVIDENCE: Prospective cohort study, Level II.

Analysis of Task Attributes Associated with Crisis Checklist Compliance in Pediatric Trauma Resuscitation.

Although checklists can improve overall team performance during medical crises, non-compliant checklist use poses risks to patient safety. We examined how task attributes affected checklist compliance by studying the use of a digital checklist during trauma resuscitation. We first determined task attributes and checklist compliance behaviors for 3,131 resuscitation tasks. Using statistical analyses and qualitative video review, we then identified barriers to accurately tracking task status, finding that certain task attributes were associated with non-compliant checklist behaviors. For example, tasks with multiple steps were more likely to be incorrectly recorded as completed when the task was not performed to completion. We discuss challenges in capturing and tracking the status of tasks with attributes that contribute to non-compliant checklist use. We also contribute a framework for understanding how tasks with certain attributes can be designed on checklists to improve compliance.

Inflammation of the retinal pigment epithelium drives early-onset photoreceptor degeneration in Mertk-associated retinitis pigmentosa.

Severe, early-onset photoreceptor (PR) degeneration associated with MERTK mutations is thought to result from failed phagocytosis by retinal pigment epithelium (RPE). Notwithstanding, the severity and onset of PR degeneration in mouse models of Mertk ablation are determined by the hypomorphic expression or the loss of the Mertk paralog Tyro3. Here, we find that loss of Mertk and reduced expression/loss of Tyro3 led to RPE inflammation even before eye-opening. Incipient RPE inflammation cascaded to involve microglia activation and PR degeneration with monocyte infiltration. Inhibition of RPE inflammation with the JAK1/2 inhibitor ruxolitinib mitigated PR degeneration in Mertk-/- mice. Neither inflammation nor severe, early-onset PR degeneration was observed in mice with defective phagocytosis alone. Thus, inflammation drives severe, early-onset PR degeneration-associated with Mertk loss of function.

Crystalloid volume is associated with short-term morbidity in children with severe traumatic brain injury: An Eastern Association for the Surgery of Trauma multicenter trial post hoc analysis.

OBJECTIVE: This study examined differences in clinical and resuscitation characteristics between injured children with and without severe traumatic brain injury (sTBI) and aimed to identify resuscitation characteristics associated with improved outcomes following sTBI. METHODS: This is a post hoc analysis of a prospective observational study of injured children younger than 18 years (2018-2019) transported from the scene, with elevated shock index pediatric-adjusted on arrival and head Abbreviated Injury Scale score of ≥3. Timing and volume of resuscitation products were assessed using χ 2t test, Fisher's exact t test, Kruskal-Wallis, and multivariable logistic regression analyses. RESULTS: There were 142 patients with sTBI and 547 with non-sTBI injuries. Severe traumatic brain injury patients had lower initial hemoglobin (11.3 vs. 12.4, p < 0.001), greater initial international normalized ratio (1.4 vs. 1.1, p < 0.001), greater Injury Severity Score (25 vs. 5, p < 0.001), greater rates of ventilator (59% vs. 11%, p < 0.001) and intensive care unit (ICU) requirement (79% vs. 27%, p < 0.001), and more inpatient complications (18% vs. 3.3%, p < 0.001). Severe traumatic brain injury patients received more prehospital crystalloid (25% vs. 15%, p = 0.008), ≥1 crystalloid boluses (52% vs. 24%, p < 0.001), and blood transfusion (44% vs. 12%, p < 0.001) than non-sTBI patients. Among sTBI patients, receipt of ≥1 crystalloid bolus (n = 75) was associated with greater ICU need (92% vs. 64%, p < 0.001), longer median ICU (6 vs. 4 days, p = 0.027) and hospital stay (9 vs. 4 days, p < 0.001), and more in-hospital complications (31% vs. 7.5%, p = 0.003) than those who received <1 bolus (n = 67). These findings persisted after adjustment for Injury Severity Score (odds ratio, 3.4-4.4; all p < 0.010). CONCLUSION: Pediatric trauma patients with sTBI received more crystalloid than those without sTBI despite having a greater international normalized ratio at presentation and more frequently requiring blood products. Excessive crystalloid may be associated with worsened outcomes, including in-hospital mortality, seen among pediatric sTBI patients who received ≥1 crystalloid bolus. Further attention to a crystalloid sparing, early transfusion approach to resuscitation of children with sTBI is needed. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Necrotizing soft tissue infection of the forearms in a patient using intravenous heroin: case report of advanced wound management improving dressing tolerance and expediting skin graft.

BACKGROUND: Necrotizing soft tissue infection (NSTI) is rare and characterized by rapid onset and spread of inflammation and necrosis. The infection starts within the fascia but can rapidly progress to include musculature, subcutaneous fat, and overlying skin. Its presentation is considered a surgical emergency. Persons who use intravenous or subcutaneous opioids are at higher risk of NSTIs. PURPOSE: The purpose of this case report is to describe the positive clinical outcome after consulting with wound specialists and using a dressing regimen to expedite more rapid wound healing, shortened time to skin graft, and improved pain tolerance in a patient with a history of intravenous and subcutaneous heroin use. CASE REPORT: The patient presented with an NSTI that required extensive debridement of the bilateral upper extremities. The acute surgical wound service was consulted. A dressing regimen consisting of hypochlorous acid-preserved wound cleansing, followed by carboxymethylcellulose fiber with 1.2% ionic silver covered by hydrocellular foam to promote a moist healing environment, was used to facilitate granulation. RESULTS: Healthy granulation tissue was noted 6 days after debridement. The improved rate of granulation and the patient's tolerance to dressing changes secondary to decreased pain from these dressings significantly expedited the time to graft and wound healing. The patient underwent split-thickness skin grafting 10 days after debridement. There was 100% uptake of the grafts on postgraft day 8. CONCLUSION: The favorable clinical outcome suggests that early consultation with wound specialists and implementation of the dressing regimen were effective in this patient regarding improved pain control and healing. However, because the patient left against medical advice on hospital day 20, the clinical course could not be followed beyond the first few postoperative weeks.

A Retrospective Health Economic Analysis of a Stable Hypochlorous Acid Preserved Wound Cleanser Versus 0.9% Saline Solution as Instillation for Negative-Pressure Wound Therapy in Severe and Infected Wounds.

Introduction Negative-pressure wound therapy (NPWT) with instillation and dwell time is an accepted adjunct therapy for infected wounds. A study was conducted to assess whether the use of hypochlorous acid preserved wound cleanser (HAPWOC) (Vashe, Urgo Medical North America, Fort Worth, TX, USA) as the irrigant would reduce the cost of care in comparison to 0.9% saline (NaCl). Method A comparative, observational, retrospective analysis assessed 27 serious and infected wounds in 24 patients. The lesions were of different and complex etiologies, including necrotizing fasciitis and stage IV diabetic foot ulcers. NPWT was used as part of the overall multimodal treatment regimen. The only variance in the treatment protocol was the use of saline (N=8) or HAPWOC (N=19) as the irrigant. Results When compared to NaCl, wounds treated with HAPWOC trended toward fewer operating room (OR) visits versus NaCl (3.3 versus 4.1) and a shorter length of hospital stay (LOS) (24.3 days versus 37.9 days). The Orlando Health Transparency guide shows the cost of OR debridement as $2,525. Thus, debridement for HAPWOC-treated wounds ($8,332) costs $2,020 (24%) less than for NaCl-treated wounds ($10,352). Using the 2016 Kaiser Health data (average daily hospital cost, excludingall interventions: $2,052), the cost of HAPWOC and NaCl instill translates to $49,864 and $77,771, respectively, a difference of $27,906 (56%) more for NaCl treatment. The Agency for Healthcare Research and Quality (AHRQ) 2012 data indicate an average daily cost of hospital stay, including all interventions, of $10,400. Thus, HAPWOC treatment cost translates to $252,720 versus NaCl-related costs of $394,160; in these calculations, using NaCl costs $141.440 (+56%) more per patient than HAPWOC. Conclusion The use of NPWT with HAPWOC versus NaCl as instillation in NPWT reduces the number of visits to the operating room and LOS. This has a significant impact on lowering the cost of care when HAPWOC is used.

A Pilot Study Using a Collagen/Oxidized Regenerative Cellulose Dressing for Split- Thickness Skin Graft Donor Sites to Reduce Pain and Bleeding Complications.

BACKGROUND: Standardized treatment of split-thickness skin graft (STSG) donor sites is not established. Bleeding can necessitate premature dressing changes, interrupting the healing process and increasing pain. PURPOSE: A collagen/oxidized regenerated cellulose (C/ORC) dressing was used on the donor site. The authors hypothesized that the collagen matrix could decrease bleeding-related complications, reduce pain, and foster epithelialization. METHODS: The C/ORC matrix was applied to the donor site after hemostasis was achieved. Dressings were removed between postoperative days 4 and 7, and the patients' pain levels, bleeding complications, and percentage healed were recorded. RESULTS: Thirty-nine patients were treated with the C/ORC donor site dressing. Of these, 35 patients (89.7%) were receiving at least prophylactic anticoagulation, and no bleeding complications were recorded. The average area of donor sites was 123.8 cm2 (range, 20-528 cm2). Utilizing the Numerical Rating Scale, 25 patients (64.1%) reported no pain with dressing removal while 5 (12.8%) reported a decrease in pain. The percentage of epithelialization as assessed by treating clinician was at least equivalent to other modalities. CONCLUSIONS: The application of a C/ORC matrix to STSG donor wound sites resulted in no bleeding complications and excellent pain control while promoting epithelialization in the patients studied. Following this study, the C/ORC dressing has been incorporated into the authors' standard protocol.

Derivation and validation of an improved pediatric shock index for predicting need for early intervention and outcomes in pediatric trauma.

BACKGROUND: Shock index, pediatric age adjusted (SIPA), has been widely applied in pediatric trauma but has limited precision because of the reference ranges used in its derivation. We hypothesized that a pediatric shock index (PSI) equation based on age-based vital signs would outperform SIPA. METHODS: A retrospective cohort of trauma patients aged 1 to 18 years from Trauma Quality Programs - Participant Use File 2010 to 2018 was performed. A random 70% training subset was used to derive Youden index-optimizing shock index (SI) cutoffs by age for blood transfusion within 4 hours. We used linear regression to derive equations representing the PSI cutoff for children 12 years or younger and 13 years or older. For children 13 years or older, the well-established SI of 0.9 remained optimal, consistent with SIPA and other indices. For children 12 years or younger in the 30% validation subset, we compared our age-based PSI to SIPA as predictors of early transfusion, mortality, pediatric intensive care unit admission, and injury severity score of ≥25. For bedside use, a simplified "rapid" pediatric shock index (rPSI) equation was also derived and compared with SIPA. RESULTS: A total of 439,699 patients aged 1 to 12 years met the inclusion criteria with 2,718 (1.3% of those with available outcome data) requiring transfusion within 4 hours of presentation. In the validation set, positive predictive values for early transfusion were higher for PSI (8.3%; 95% confidence interval [CI], 7.5-9.1%) and rPSI (6.3%; 95% CI, 5.7-6.9%) than SIPA (4.3%; 95% CI, 3.9-4.7%). For early transfusion, negative predictive values for both PSI (99.3%; 95% CI, 99.2-99.3%) and rPSI (99.3%; 95% CI, 99.2-99.4%) were similar to SIPA (99.4%; 95% CI, 99.3-99.4%). CONCLUSION: We derived the PSI and rPSI for use in pediatric trauma using empiric, age-based SI cutoffs. The PSI and rPSI achieved higher positive predictive values and similar negative predictive values to SIPA in predicting the need for early blood transfusion and mortality. LEVEL OF EVIDENCE: Prognostic/Epidemiological; level III.

Reducing the Time to Blood Administration after Pediatric Injury: A Quality Improvement Initiative.

Introduction: Hemorrhage is the leading cause of preventable death in pediatric trauma patients. Timely blood administration is associated with improved outcomes in children and adults. This study aimed to identify delays to transfusion and improve the time to blood administration among injured children. Methods: A multidisciplinary team identified three activities associated with blood transfusion delays during the acute resuscitation of injured children. To address delays related to these activities, we relocated the storage of un-crossmatched blood to the emergency department (ED), created and disseminated an intravenous access algorithm, and established a nursing educator role for resuscitations. We performed comparative and regression analyses to identify the impact of these factors on the timeliness and likelihood of blood administration. Results: From January 2017 to June 2021, we treated 2159 injured children and adolescents in the resuscitation area, 54 (2.5%) of whom received blood products in the ED. After placing a blood storage refrigerator in the ED, we observed a centerline change that lowered the adjusted time-to-blood administration to 17 minutes (SD 11), reducing the time-to-blood administration by 11 minutes (ß = -11.0, 95% CI = -22.0 to -0.9). The likelihood of blood administration was not changed after placement of the blood refrigerator. We observed no reduction in time following the implementation of the intravenous access algorithm or a nursing educator. Conclusions: Relocation of un-crossmatched blood storage to the ED decreased the time to blood transfusion. This system-based intervention should be considered a strategy for reducing delays in transfusion in time-critical settings.

Tissue-specific modifier alleles determine Mertk loss-of-function traits.

Knockout (KO) mouse models play critical roles in elucidating biological processes behind disease-associated or disease-resistant traits. As a presumed consequence of gene KO, mice display certain phenotypes. Based on insight into the molecular role of said gene in a biological process, it is inferred that the particular biological process causally underlies the trait. This approach has been crucial towards understanding the basis of pathological and/or advantageous traits associated with Mertk KO mice. Mertk KO mice suffer from severe, early-onset retinal degeneration. MERTK, expressed in retinal pigment epithelia, is a receptor tyrosine kinase with a critical role in phagocytosis of apoptotic cells or cellular debris. Therefore, early-onset, severe retinal degeneration was described to be a direct consequence of failed MERTK-mediated phagocytosis of photoreceptor outer segments by retinal pigment epithelia. Here, we report that the loss of Mertk alone is not sufficient for retinal degeneration. The widely used Mertk KO mouse carries multiple coincidental changes in its genome that affect the expression of a number of genes, including the Mertk paralog Tyro3. Retinal degeneration manifests only when the function of Tyro3 is concomitantly lost. Furthermore, Mertk KO mice display improved anti-tumor immunity. MERTK is expressed in macrophages. Therefore, enhanced anti-tumor immunity was inferred to result from the failure of macrophages to dispose of cancer cell corpses, resulting in a pro-inflammatory tumor microenvironment. The resistance against two syngeneic mouse tumor models observed in Mertk KO mice is not, however, phenocopied by the loss of Mertk alone. Neither Tyro3 nor macrophage phagocytosis by alternate genetic redundancy accounts for the absence of anti-tumor immunity. Collectively, our results indicate that context-dependent epistasis of independent modifier alleles determines Mertk KO traits.

Regulation of bone homeostasis by MERTK and TYRO3.

The fine equilibrium of bone homeostasis is maintained by bone-forming osteoblasts and bone-resorbing osteoclasts. Here, we show that TAM receptors MERTK and TYRO3 exert reciprocal effects in osteoblast biology: Osteoblast-targeted deletion of MERTK promotes increased bone mass in healthy mice and mice with cancer-induced bone loss, whereas knockout of TYRO3 in osteoblasts shows the opposite phenotype. Functionally, the interaction of MERTK with its ligand PROS1 negatively regulates osteoblast differentiation via inducing the VAV2-RHOA-ROCK axis leading to increased cell contractility and motility while TYRO3 antagonizes this effect. Consequently, pharmacologic MERTK blockade by the small molecule inhibitor R992 increases osteoblast numbers and bone formation in mice. Furthermore, R992 counteracts cancer-induced bone loss, reduces bone metastasis and prolongs survival in preclinical models of multiple myeloma, breast- and lung cancer. In summary, MERTK and TYRO3 represent potent regulators of bone homeostasis with cell-type specific functions and MERTK blockade represents an osteoanabolic therapy with implications in cancer and beyond.