Presence of Microscopic Hematuria Does Not Predict Clinically Important Intra-Abdominal Injury in Children.

OBJECTIVE: Screening for blunt intra-abdominal injury in children often includes directed laboratory evaluation that guides need for computed tomography. We sought to evaluate the use of urinalysis in identifying patients with clinically important intraabdominal injury (ci-IAI). METHODS: A retrospective chart review was performed for all patients less than 18 years who presented with blunt mechanisms at a level I trauma center between 2016 and 2019. Exclusion criteria included transfer from an outside facility, physical abuse, and death within thirty minutes of arrival. Demographics, physical exam findings, serum chemistries, urinalysis, and imaging were reviewed. Clinically important intraabdominal injury was defined as injury requiring ≥2 nights admission, blood transfusion, angiography with embolization, or therapeutic surgery. RESULTS: Two hundred forty patients were identified. One hundred sixty-five had a completed urinalysis. For all patients an abnormal chemistry panel and abnormal physical exam had a sensitivity of 88.9% and a negative predictive value of 99.3%. Nine patients had a ci-IAI. Patients with a ci-IAI were more likely to have abdominal pain, tenderness on exam, and elevated hepatic enzymes. When patients were stratified by the presence of an abnormal chemistry or physical exam with or without microscopic hematuria, urinalysis did not improve the ability to identify patients with a ci-IAI. In fact, presence of microscopic hematuria increased the rate of false positives by 12%. CONCLUSIONS: Microscopic hematuria was not a useful marker for ci-IAI and may lead to falsely assuming a more serious injury.

Derivation and Validation of a Machine Learning Algorithm for Predicting Venous Thromboembolism in Injured Children.

BACKGROUND: Venous thromboembolism (VTE) causes significant morbidity in pediatric trauma patients. We applied machine learning algorithms to the Trauma Quality Improvement Program (TQIP) database to develop and validate a risk prediction model for VTE in injured children. METHODS: Patients ≤18 years were identified from TQIP (2017-2019, n = 383,814). Those administered VTE prophylaxis ≤24 h and missing the outcome (VTE) were removed (n = 347,576). Feature selection identified 15 predictors: intubation, need for supplemental oxygen, spinal injury, pelvic fractures, multiple long bone fractures, major surgery (neurosurgery, thoracic, orthopedic, vascular), age, transfusion requirement, intracranial pressure monitor or external ventricular drain placement, and low Glasgow Coma Scale score. Data was split into training (n = 251,409) and testing (n = 118,175) subsets. Machine learning algorithms were trained, tested, and compared. RESULTS: Low-risk prediction: For the testing subset, all models outperformed the baseline rate of VTE (0.15%) with a predicted rate of 0.01-0.02% (p < 2.2e-16). 88.4-89.4% of patients were classified as low risk by the models. HIGH-RISK PREDICTION: All models outperformed baseline with a predicted rate of VTE ranging from 1.13 to 1.32% (p < 2.2e-16). The performance of the 3 models was not significantly different. CONCLUSION: We developed a predictive model that differentiates injured children for development of VTE with high discrimination and can guide prophylaxis use. LEVEL OF EVIDENCE: Prognostic, Level II. TYPE OF STUDY: Retrospective, Cross-sectional.

Obesity is not associated with increased resource utilization or morbidity in patients undergoing appendectomy.

BACKGROUND: Obesity is a growing public health concern that places patients at risk of morbidity and mortality following surgery. We sought to determine whether obesity influences our resource utilization and postoperative outcomes for patients who present with appendicitis. METHODS: Charts were reviewed for patients age 1-18 years identified from a prospective registry who presented with a diagnosis of appendicitis from 2017 to 2020. Patients who underwent appendectomy were eligible. Charts were reviewed for demographics, imaging studies, laboratory studies, length of stay, operative times and thirty-day postoperative adverse events defined as return to the emergency room, re-admission, postoperative abscess or return to the operating room. A multivariate logistic regression analysis was performed to identify differences in resource utilization and outcome. RESULTS: A total of 451 patients were identified. There were 126 obese patients (27.9%). Obese patients were not more likely to present with perforated appendicitis and were not more likely to undergo computed tomography scans. All patients underwent laparoscopic appendectomy. Although intraoperative times were significantly longer for Black patients and older patients, BMI did not influence length of surgery. Length of stay was significantly higher for younger patients (p = 0.019). Adverse events were seen in 38 patients (8.4%). There was no association between BMI and adverse events. CONCLUSIONS: Within our standardized management pathway, obesity does not influence management or patient outcomes for the treatment of appendicitis. Furthermore, obese patients did not require additional resource utilization. LEVEL OF EVIDENCE: III.

Human CD19-specific switchable CAR T-cells are efficacious as constitutively active CAR T-cells but cause less morbidity in a mouse model of human CD19+ malignancy.

Current Food and Drug Administration (FDA)-approved CD19-specific chimeric antigen receptor (CAR) T-cell therapies for B-cell malignancies are constitutively active and while efficacious, can cause morbidity and mortality. Their toxicities might be reduced if CAR T-cell activity was regulatable rather than constitutive. To test this, we compared the efficacies and morbidities of constitutively active (conventional) and regulatable (switchable) CAR (sCAR) T-cells specific for human CD19 (huCD19) in an immune-competent huCD19+ transgenic mouse model.Conventional CAR (CAR19) and sCAR T-cells were generated by retrovirally transducing C57BL/6 (B6) congenic T-cells with constructs encoding antibody-derived single chain Fv (sFv) fragments specific for huCD19 or a peptide neoepitope (PNE), respectively. Transduced T-cells were adoptively transferred into huCD19 transgenic hemizygous (huCD19Tg/0 ) B6 mice; healthy B-cells in these mice expressed huCD19Tg Prior to transfer, recipients were treated with a lymphodepleting dose of cyclophosphamide to enhance T-cell engraftment. In tumor therapy experiments, CAR19 or sCAR T-cells were adoptively transferred into huCD19Tg/0 mice bearing a syngeneic B-cell lymphoma engineered to express huCD19. To regulate sCAR T cell function, a switch protein was generated that contained the sCAR-specific PNE genetically fused to an anti-huCD19 Fab fragment. Recipients of sCAR T-cells were injected with the switch to link sCAR effector with huCD19+ target cells. Mice were monitored for survival, tumor burden (where appropriate), morbidity (as measured by weight loss and clinical scores), and peripheral blood lymphocyte frequency.CAR19 and sCAR T-cells functioned comparably regarding in vivo expansion and B-cell depletion. However, sCAR T-cells were better tolerated as evidenced by the recipients' enhanced survival, reduced weight loss, and improved clinical scores. Discontinuing switch administration allowed healthy B-cell frequencies to return to pretreatment levels.In our mouse model, sCAR T-cells killed huCD19+ healthy and malignant B-cells and were better tolerated than CAR19 cells. Our data suggest sCAR might be clinically superior to the current FDA-approved therapies for B-cell lymphomas due to the reduced acute and chronic morbidities and mortality, lower incidence and severity of side effects, and B-cell reconstitution on cessation of switch administration.

Murine CAR19 Tregs suppress acute graft-versus-host disease and maintain graft-versus-tumor responses.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) efficacy is complicated by graft-versus-host disease (GVHD), a leading cause of morbidity and mortality. Regulatory T cells (Tregs) have shown efficacy in preventing GVHD. However, high Treg doses are often required, necessitating substantial ex vivo or in vivo expansion that may diminish suppressor function. To enhance in vivo suppressor function, murine Tregs were transduced to express an anti-human CD19 chimeric antigen receptor (hCAR19) and infused into lethally irradiated, hCD19-transgenic recipients for allo-HSCT. Compared with recipients receiving control transduced Tregs, those receiving hCAR19 Tregs had a marked decrease in acute GVHD lethality. Recipient hCD19 B cells and murine hCD19 TBL12-luciferase (TBL12luc) lymphoma cells were both cleared by allogeneic hCAR19 Tregs, which was indicative of graft-versus-tumor (GVT) maintenance and potentiation. Mechanistically, hCAR19 Tregs killed syngeneic hCD19+ but not hCD19- murine TBL12luc cells in vitro in a perforin-dependent, granzyme B-independent manner. Importantly, cyclophosphamide-treated, hCD19-transgenic mice given hCAR19 cytotoxic T lymphocytes without allo-HSCT experienced rapid lethality due to systemic toxicity that has been associated with proinflammatory cytokine release; in contrast, hCAR19 Treg suppressor function enabled avoidance of this severe complication. In conclusion, hCAR19 Tregs are a potentially novel and effective strategy to suppress GVHD without loss of GVT responses.

Pediatric Train Injuries: A 10-Year Review From the Pennsylvania Trauma Outcomes Study Database.

OBJECTIVES: Trains can cause severe injuries in pediatric patients requiring significant resource utilization. We sought to review train injuries in Pennsylvania to determine the burden of these injuries on the pediatric trauma system. METHODS: We queried the Pennsylvania Trauma Outcomes Study Database to identify patients younger than 18 years injured by trains between 2007 and 2016. Demographics, hospital course, outcomes, and resource utilization were reviewed. RESULTS: Thirty-five children from 17 Pennsylvania counties were included. Three counties accounted for 48.6% of injured children. The median age was 15.0 years, and most patients were White (60.0%) and male (77.1%). The median length of stay was 8.0 days and overall mortality 8.6%. Intensive care unit admission was required for 65.7%. The median Injury Severity and Functional Status at Discharge scores were 14.0 and 18.0, respectively. Major orthopedic injuries (fracture or amputation) were the most common (57.1%) followed by traumatic brain injury (45.7%), pneumothorax (14.3%), and solid organ injury (14.3%). Operative management was common with 65.7% undergoing surgery. CONCLUSIONS: Injuries caused by trains can be severe and are most commonly orthopedic or traumatic brain injuries. Targeted safety interventions may be possible given the common mechanisms and geographic clustering of these injuries.

Pediatric Covid-19 mesenteric lymphoid hyperplasia associated intussusception: A case report and literature review.

A 2 month old, full term, previously healthy male, with known COVID-19 infection 3 weeks prior to arrival presented to the Emergency Department (ED) with complaints of 5-6 episodes of non-bilious and non-bloody emesis. According to the child's parents, the emesis was mostly associated with feeding. His parents endorsed that the patient had one episode of diarrhea that was maroon in color and appeared different than typical stools. Abdominal exam at that time was non distended with no tenderness and no other significant findings. The patient was observed while feeding in the ED and was noted to have some minimal spit up with arching of his back. A presumptive diagnosis of reflux was made, and the patient was discharged home with education on feeding. The infant was brought back to the ED the following day due to worsening emesis. Additionally, his parents noted more episodes of bloody stools. His abdomen appeared mildly distended with moderate tenderness on abdominal examination. During evaluation, a large "currant jelly" stool was observed (Fig. 1). An abdominal ultrasound was obtained, which demonstrated an ileocolic intussusception with a possible enlarged lymph node as lead point. The patient received an air contrast enema with successful reduction. Repeat ultrasound was obtained which confirmed resolution, and the patient was admitted for overnight observation. The patient tested positive for SARS-CoV-2 using polymerase chain reaction testing. He was discharged the following day after successful advancing of diet, normal serial abdominal exams, and observed normal bowel movements.

Actinomycosis: Case report of an unusual cause of diaphragmatic herniation.

INTRODUCTION: We present a case of actinomycosis which resulted in a symptomatic diaphragmatic hernia requiring operative repair, an unusual complication not found in the literature. Actinomycosis is a chronic, slowly progressive infection caused by the bacterial genus Actinomyces which characteristically causes necrosis and abscess formation in a myriad of organ systems. CASE PRESENTATION: A 5 year old male presented with nonspecific symptoms which were, after a short delay, identified as actinomycosis and treated with appropriate antibiosis. His infection was complicated by development of a diaphragmatic hernia, which subsequently became symptomatic and required surgical repair. CLINICAL DISCUSSION: While this diaphragmatic hernia is an unusual complication of actinomycosis not previously found in the literature, the patient's delayed diagnosis of the infection is typical. Surgical intervention was warranted for symptoms of the sequelae of the disease, not control of the disease itself. CONCLUSION: Laparoscopic repair of the multiple diaphragmatic defects was successful with a intraperitoneal on-lay biologic mesh, with resolution of symptoms. It is possible the need for surgical intervention in future cases of actinomycosis could be avoided with higher index of suspicion leading to earlier diagnosis.

Utility of skull radiographs in infants undergoing 3D head CT during evaluation for physical abuse.

BACKGROUND: Clinical practice guidelines recommend performing head CT and skull radiographs (SR) when evaluating infants for physical abuse. We compared the accuracy of 3-dimensional CT (3DCT) and SR for detecting skull fractures. METHODS: We reviewed children <12 months evaluated for physical abuse undergoing 3DCT and SR between January 2017 and December 2018. 3DCT and SR images were blindly read by 2 radiologists. Interrater reliability (IRR) was calculated. Diagnostic accuracy was compared using McNemar's test. RESULTS: 158 infants with a mean age of 5.0 months underwent 3DCT and SR. Consensus reading identified 46 fractures (29.1%) on 3DCT and 40 fractures (25.3%) on SR. IRR was higher for 3DCT (κ = 0.95) than for SR (=0.65). 11 fractures were identified on 3DCT but not SR. 5 fractures were identified on SR but not 3DCT. There was no difference in the diagnostic accuracy of 3DCT and SR (χ2 = 1.56, p = 0.211). CONCLUSIONS: We found no difference in the accuracy of 3DCT and SR for detecting skull fractures in infants. Because 3DCT has better IRR and evaluates for both bony and intracranial injuries it is superior to SR. Omitting SRs may be acceptable if a 3DCT is performed, and would reduce radiation exposure without compromising diagnostic accuracy.

Preoperative Embolization Facilitates Segmental Resection of Pulmonary Sequestration in an Infant.

The most common congenital lung malformations are congenital pulmonary airway malformations and pulmonary sequestrations. Many surgeons advocate resection to prevent complications of infection, malignancy, and pneumothorax. The standard of care is lobectomy, but segmentectomy and embolization alone have been reported. These methods avoid the complications of lobectomy but are not widely practiced due to concerns about incomplete resection or involution of the lesion. We present a novel approach to the treatment of a pulmonary sequestration in a 7-month-old male using preoperative embolization followed by a sublobar pulmonary resection. The embolization clearly demarcated the affected lung intraoperatively, thereby facilitating complete removal of the lesion with a segmental lung resection rather than complete lobectomy.

Effect of Feeding Strategies on the Development of Fulminant Necrotizing Enterocolitis.

INTRODUCTION: Necrotizing enterocolitis (NEC) causes significant neonatal morbidity. A subset of infants experience precipitous decline and death from fulminant-NEC (F-NEC). We sought to determine the effect of feeding practices on the development of this more virulent form of NEC. MATERIALS AND METHODS: Premature neonates developing Bell's stage II or III NEC between May 2011 and June 2017 were reviewed. Infants were stratified as having NEC or F-NEC, defined as NEC-totalis or NEC causing rapid decline and death within 72 hours. Risk factors extracted included demographics, gestational age, and weight at NEC diagnosis. Feeding data extracted included age at first feed, caloric density, type of feed (breast milk or formula), and whether full volume feeds were reached. Univariate analysis and multivariate analysis were performed. RESULTS: A total of 98 patients were identified, of which 80 were included. In total, 57 patients had NEC and 23 had F-NEC. Reaching full volume feeds was associated with F-NEC on both univariate and multivariate analysis (37.9 vs. 4.5%; odds ratio: 67, 95% confidence interval: 6.606-2041, p = 0.003). Infants developing F-NEC achieved full feeds earlier (22.5 vs. 19.8 days, p = 0.025) on univariate but not multivariate analysis. There was no difference in the rates of NEC and F-NEC among infants receiving breast milk (standard or fortified) or formula (standard or increased caloric density; p = 0.235). CONCLUSION: Among premature neonates with NEC, reaching full volume feedings was associated with a nearly 70-fold increased risk of F-NEC. Assuming it was possible to predict an infant's development of NEC, alternative feeding regimens might reduce the risk of F-NEC in this population.

A Standardized Protocol for Nonoperative Management of Complicated Appendicitis in Children Reduces Resource Utilization.

INTRODUCTION: To standardize care and reduce resource utilization, we implemented a standardized protocol (SP) for the nonoperative treatment of complicated appendicitis. MATERIALS AND METHODS: We conducted a prospective, historically controlled, study of patients <21 years with complicated appendicitis managed nonoperatively using an SP from January 2017 to November 2018. The primary outcomes included length of stay (LOS), antibiotic days, peripheral inserted central catheter (PICC) utilization, discharge on intravenous antibiotics, and predischarge imaging. Secondary outcomes were protocol adherence and the rates of adverse events (AE) including return to emergency department (ED), readmission, failure of nonoperative treatment, and interval appendectomy complications. RESULTS: Protocol adherence was 67.9%. In total, 741 children were treated for appendicitis of which 58 (30 pre-SP and 28 post-SP) were treated nonoperatively for complicated appendicitis at presentation. Patients were well matched for age, admission white blood cell, sex, body mass index, race, and the proportion requiring percutaneous drainage. After implementing the SP, fewer children had PICCs (100.0 vs. 57.1%, p ≤ 0.001), fewer were discharged on intravenous antibiotics (90.0 vs. 42.9%, p < 0.001), and total antibiotic days were reduced (14.0 vs. 10.0, p = 0.006). There was no difference in LOS (5.5 vs. 6.0 days, p = 0.790) or the proportion undergoing ultrasound (36.7 vs. 39.3%, p = 0.837) or computed tomography scan (16.7 vs. 3.6%, p = 0.195) prior to discharge. There were nonsignificant trends toward reduced AEs (46.7 vs. 35.7%, p = 0.397), returns to ED (40.0 vs. 28.6%, p = 0.360), and readmissions (26.7 vs. 17.9%, p = 0.421). The proportion failing nonoperative treatment (10.0 vs. 3.6%, p = 0.612) and experiencing complications of interval appendectomy (3.3 vs. 3.6%, p = 0.918) were not significantly different. CONCLUSION: Implementing an SP for treating complicated appendicitis nonoperatively reduced resource utilization without negatively affecting clinical outcomes.

A Standardized Protocol for the Management of Appendicitis in Children Reduces Resource Utilization.

Appendicitis is the most common condition requiring emergency surgery in children. We implemented a standardized protocol (SP) for treating children with appendicitis to provide more uniform care and reduce resource utilization. METHODS: All patients younger than 21 years were managed with the SP beginning in January 2017. We compared data from 22 months before and after implementation. The primary outcomes included the length of stay (LOS), antibiotic days, discharge on intravenous antibiotics, utilization of peripherally inserted central catheters lines, and postoperative imaging. Secondary outcomes were protocol adherence and the rates adverse events, including postoperative abscess, return to emergency department or operating room, surgical site infection, and readmission. RESULTS: Protocol adherence was 92.3%. For uncomplicated cases (n = 412), LOS (P = 0.010) and postoperative antibiotic days (P < 0.001) were significantly reduced. There was no difference in the rates of any adverse event (6.7% versus 2.7%; P = 0.058), postoperative abscess (0.4% versus 0.0%; P = 0.544), return to emergency department (6.3% versus 2.7%; P = 0.084), readmission (1.8% versus 0.5%; P = 0.245), or postoperative ultrasound (0.4% versus 0.5%; P = 0.705) and computed tomography (0.0% versus 0.5%; P = 0.456). For complicated cases (n = 229), the post-SP cohort had a shorter LOS (P = 0.015), fewer peripherally inserted central catheters lines (26.9% versus 2.7%; P < 0.001), fewer postoperative ultrasounds (8.4% versus 1.8%; P = 0.027), and fewer discharges on intravenous antibiotics (17.6% versus 0.9%; P < 0.001). There were no differences in adverse events before and after the SP (16.0% versus 18.3%; P = 0.633). CONCLUSION: Implementing an SP for appendicitis in children reduced resource utilization, and by inference healthcare costs, for both uncomplicated and complicated cases without adversely affecting clinical outcomes.

A Standardized Protocol for Cervical Spine Evaluation in Children Reduces Imaging Utilization: A Pilot Study of the Pediatric Cervical Spine Clearance Working Group Protocol.

BACKGROUND: Cervical spine injuries (CSI) have the potential to cause severe morbidity in children. Multiple imaging studies are used during evaluation of CSIs but come at a cost, both financially and in radiation exposure. To reduce resource utilization and radiation exposure, we implemented the Pediatric Cervical Spine Clearance Working Group (PCSCWG) standardized protocol (SP) for evaluating CSIs in children. METHODS: Children below 18 years old presenting with concern for CSI at a level 1 pediatric trauma center were reviewed before (July 2015 to May 2016) and after (November 2017 to June 2018) protocol implementation. Demographics, injuries, and imaging utilization were extracted. The primary outcomes were the proportion of patients cleared with clinical exam, and the proportion undergoing x-ray, computed tomography, or magnetic resonance image. The secondary outcome was the estimated difference in imaging charges based on the annual reduction in radiographic studies. RESULTS: During the study 359 children were evaluated for CSIs (248 pre-SP, 111 post-SP). Patients were similar with respect to age, injury severity score, and mechanism of injury. Protocol adherence was 87.4%. The prevalence of CSI was similar in the preprotocol and postprotocol cohorts (2.8% vs. 1.8%, P=0.567). Children treated after protocol implementation were significantly more likely to be cleared by clinical exam (15.3% vs. 43.2%, P<0.001). Significantly fewer children had x-rays (70.2% vs. 55.0%, P=0.005) and computed tomography scans (14.5% vs. 5.4%, P=0.013) in the postprotocol period. There was no difference in the utilization of magnetic resonance image (6.9% vs. 7.2%, P=0.904) or the proportion of children discharged with a cervical collar (10.1% vs. 12.6%, P=0.476). No patients in either group were found to have a previously undiagnosed injury at follow-up. The reduction in radiographic studies translates to an estimated annual reduction in imaging charges of $396,476. CONCLUSIONS: The PCSCWG protocol for evaluating CSIs reduced the number of radiographic studies performed and estimated imaging charges while reliably identifying CSIs.

Risk assessment for intra-abdominal injury following blunt trauma in children: Derivation and validation of a machine learning model.

BACKGROUND: Computed tomography is the criterion standard for diagnosing intra-abdominal injury (IAI) but is expensive and risks radiation exposure. The Pediatric Emergency Care Applied Research Network (PECARN) model identifies children at low risk of IAI requiring intervention (IAI-I) in whom computed tomography may be omitted but does not provide an individualized risk assessment to positively predict IAI-I. We sought to apply machine learning algorithms to the PECARN blunt abdominal trauma (BAT) data set experimentally to create models for predicting both the presence and absence of IAI-I for pediatric BAT victims. METHODS: Using the PECARN data set, we derived and validated predictive models for IAI-I. The data set was divided into derivation (n = 7,940) and validation (n = 4,089) subsets. Six algorithms were tested to create 2 models using 19 clinical variables including emesis, dyspnea, Glasgow Coma Scale score of <15, visible thoracic or abdominal trauma, seatbelt sign, abdominal distension, tenderness or rectal bleeding, peritoneal signs, absent bowel sounds, flank pain, pelvic pain or instability, sex, age, heart rate, and respiratory rate (RR). Five algorithms were fitted to predict the absence (low-risk model) or presence (high-risk model) of IAI-I. Models were validated using the test subset. RESULTS: For the low-risk model, four algorithms were significantly better than the baseline rate (2.28%) when validated using the test set. The random forest model identified 73% of children as low risk, having a predicted IAI-I rate of 0.54%. For the high-risk model, all six algorithms had added predictive power compared with the baseline rate with the highest reportable risk being 39.0%. By incorporating both models into a web application, child-specific risks of IAI-I can be estimated ranging from 0.28% to 39.0% CONCLUSION: We developed a tool that provides a child-specific risk estimate for IAI-I after BAT. This publically available model provides a powerful tool for clinicians triaging pediatric victims of blunt abdominal trauma. LEVEL OF EVIDENCE: Prognostic, Level II.

Adherence to PECARN criteria in children transferred to a pediatric trauma center: An opportunity for improvement?

BACKGROUND: The Pediatric Emergency Care Applied Research Network (PECARN) criteria identify children at low risk of clinically important traumatic brain injury (ciTBI) in whom CT head (CTH) is unnecessary. We assessed compliance with PECARN at outside hospitals (OSH) among children transferred to our pediatric trauma center. METHODS: Patients <18 years transferred between May 2016 and December 2018 undergoing CTH at an OSH were reviewed. A ciTBI was defined as one requiring hospitalization ≥2 midnights, intubation >24 h, neurosurgical intervention, or causing death. RESULTS: 202 children were transferred after CTH. 53 were excluded for incomplete records (16), suspected abuse (33), or penetrating injury (4). Of the 149 included children, PECARN recommended CTH in 39 (26.2%), shared decision making in 79 (53.0%), and no imaging in 31 (20.8%). 26 children (17.4%) had a radiographic traumatic brain injury (rTBI) while only 6 (4.0%) had ciTBIs. Of those with ciTBIs, PECARN recommended CTH in 4 and shared decision making in 2. No child in whom CTH was not recommended had a ciTBI. 45 (30.2%) children had isolated extracranial injuries requiring transfer and 83 (55.7%) were transferred despite normal CTHs and no associated injuries. 2 (1.3%) children underwent non-emergent surgery for ciTBI. CONCLUSIONS: Compliance with PECARN was low among referring facilities with nearly 75% of CTHs being potentially avoidable with proper adherence and parental counseling. Deferring imaging until after transfer appears safe as no child underwent emergent intervention upon arrival. Early transfer and improved compliance with PECARN may reduce the number of CTHs performed.

Demystifying Cancer Immunotherapy for Lay Audiences.

Immunotherapy is now mainstream. Advertisements are ubiquitous in print and visual media for immune based-therapies for various conditions and diseases. Smaller companies that develop novel immunotherapies are often quickly acquired by larger companies. More and more clinical trials are open for immune-based therapies, particularly for immune checkpoint blockades. As such, immunologists need to engage the public in conversations about the strengths and limitations of immunotherapy, and the necessity of research in propelling the field further. In this article, we discuss approaches we have taken to convey key concepts in immunology and cancer immunotherapy to non-scientists and health care professionals without expertise in immunology. Although the devil is always in the details, basic concepts in immunology and immunotherapy can be readily conveyed using stories and analogies, some of which we present here.

Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy.

The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural killer cells, and recruiting the adaptive immune system. Viral peptide treatment of ex vivo human tumors recapitulates immune activation gene expression profiles observed in mice. Lastly, peptide therapy renders resistant mouse tumors susceptible to PD-L1 blockade. Thus, re-stimulating known antiviral immunity may provide a unique therapeutic approach for cancer immunotherapy.

Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma.

Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the capacity of antigen-presenting cells to prime T-cells to mediate an anti-glioma response. We found that in canine spontaneous gliomas, local injection of a canine-specific, CD200-directed peptide before subcutaneous delivery of an autologous tumor lysate vaccine prolonged survival relative to a historical control treated with autologous tumor lysate alone (median survivals of 12.7 months and 6.36 months, respectively). Antigen-presenting cells and T-lymphocytes primed with this peptide suppressed their expression of the inhibitory CD200 receptor, thereby enhancing their ability to initiate immune reactions in a glioblastoma microenvironment replete with the immunosuppressive CD200 protein. These results support consideration of a CD200 ligand as a novel glioblastoma immunotherapeutic agent.

No Surgical Innovation Without Evaluation: Evolution and Further Development of the IDEAL Framework and Recommendations.

OBJECTIVE: To update, clarify, and extend IDEAL concepts and recommendations. BACKGROUND: New surgical procedures, devices, and other complex interventions need robust evaluation for safety, efficacy, and effectiveness. Unlike new medicines, there is no internationally agreed evaluation pathway for generating and analyzing data throughout the life cycle of surgical innovations. The IDEAL Framework and Recommendations were designed to provide this pathway and they have been used increasingly since their introduction in 2009. Based on a Delphi survey, expert workshop and major discussions during IDEAL conferences held in Oxford (2016) and New York (2017), this article updates and extends the IDEAL Recommendations, identifies areas for future research, and discusses the ethical problems faced by investigators at each IDEAL stage. METHODS: The IDEAL Framework describes 5 stages of evolution for new surgical therapeutic interventions-Idea, Development, Exploration, Assessment, and Long-term Study. This comprehensive update proposes several modifications. First, a "Pre-IDEAL" stage describing preclinical studies has been added. Second we discuss potential adaptations to expand the scope of IDEAL (originally designed for surgical procedures) to accommodate therapeutic devices, through an IDEAL-D variant. Third, we explicitly recognise the value of comprehensive data collection through registries at all stages in the Framework and fourth, we examine the ethical issues that arise at each stage of IDEAL and underpin the recommendations. The Recommendations for each stage are reviewed, clarified and additional detail added. CONCLUSIONS: The intention of this article is to widen the practical use of IDEAL by clarifying the rationale for and practical details of the Recommendations. Additional research based on the experience of implementing these Recommendations is needed to further improve them.