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The Zio® (Zio) XT Patch is a 14-day continuous ambulatory ECG monitor. During the Covid-19 pandemic, Zios were mailed directly to patients for self-application. The purpose of this study was to compare the percent artifact, a marker for quality, of in-clinic (IC) to mail-home (MH) applications in a pediatric population. A single-center, IRB-approved study of patients 0- < 21 years of age with Zios was studied for wear and artifact time filtered out based on iRhythm's proprietary algorithm. In total, 284 Zios were randomly selected and analyzed for total wear time and artifact. Of these, 149 were IC prior to 12/31/2019 and 135 MH patches prescribed after 1/1/2020. No significant difference was found for percent artifact between the IC (7.8%) and MH (8.3%) group. Average IC wear-time was 127 h compared to MH at 99 h (p = 0.02). In conclusion, application of Zio patches outside of the pediatric cardiology clinic offers equivalent artifact, a marker of quality, as those applied in clinic and should be consideration as a viable alternative., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The expansion of tumor-infiltrating lymphocytes (TIL) for adoptive cellular therapy is under investigation in many solid tumors of adulthood. Marrow-infiltrating lymphocytes (MIL) have demonstrated antitumor reactivity preclinically. Successful expansion of TIL/MIL has not been reported across pediatric solid tumor histologies. The objective of this study was to demonstrate successful expansion of TIL from pediatric solid tumors for translation in an adoptive cell therapy (ACT) treatment strategy., Methods: A prospective study of TIL/MIL expansion was performed on solid tumors of pediatric patients undergoing standard-of-care procedures. TIL/MIL expansions were performed in the presence of high-dose interleukin 2. To demonstrate a full-scale expansion to clinically-relevant cell doses for TIL therapy, initial TIL culture was followed by a rapid expansion protocol for select patients. Expanded specimens were analyzed for phenotype by flow cytometry and for anti-tumor reactivity by the interferon-gamma release assay., Results: Eighteen tumor samples were obtained. Initial TIL cultures were successfully generated from 14/18 samples (77.7%). A median of 5.52 × 107 (range: 2.5 × 106-3.23 × 108) cells were produced from initial cultures, with 46.9% expressing a CD3 phenotype (46.9%). Eight samples underwent rapid expansion, demonstrating a median 458-fold expansion and a CD3 phenotype of 98%. Initial MIL cultures were successfully generated from five samples, with a predominantly CD3 phenotype (45.2%). Sufficient tumor tissue was only available for seven TIL samples to be tested for reactivity; none demonstrated responsiveness to autologous tumor., Conclusions: TIL and MIL expansion from pediatric solid tumors was successful, including the full-scale expansion process. This data supports translation to an ACT-TIL treatment strategy in the pediatric population and thus a Phase I trial of ACT-TIL in pediatric high-risk solid tumors is planned., Competing Interests: Declaration of competing interest John Mullinax (JEM): Moffitt Cancer Center has licensed Intellectual Property (IP) related to the proliferation and expansion of tumor-infiltrating lymphocytes (TILs) to Iovance Biotherapeutics. JEM is an inventor on such Intellectual Property. JEM participates in sponsored research agreements with Iovance Biotherapeutics, Intellia Therapeutics, and SQZ Biotech that are not related to this research. JEM has received research support that is not related to this research from the following entities: NIH-NCI (K08CA252642). Dr Mullinax has received ad hoc consulting fees from Merit Medical and Iovance Biotherapeutics. Shari Pilon-Thomas (SPT): Moffitt Cancer Center has licensed Intellectual Property (IP) related to the proliferation and expansion of tumor-infiltrating lymphocytes (TILs) to Iovance Biotherapeutics. Moffitt has also licensed IP to Tuhura Biopharma. SPT is an inventor on such Intellectual Property. SPT is listed as a co-inventor on a patent application with Provectus Biopharmaceuticals. SPT participates in sponsored research agreements with Provectus Biopharmaceuticals, Iovance Biotherapeutics, Intellia Therapeutics, Dyve Biosciences, Turnstone Biologics, and Celgene that are not related to this research. SPT has received research support that is not related to this research from the following entities: NIH-NCI (U01 CA244100-01, R01 CA259387, R43 CA257552-01A1, and R01 CA239219-01A1), DOD, and The Mark Foundation for Cancer Research. Dr Pilon-Thomas has received consulting fees from Seagen Inc. and KSQ Therapeutics. The remaining authors report no conflicts of interest for this study., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: Assess temporal utilization trends, identify predictors, and compare early postoperative outcomes of parathyroid autotransplantation (PTAT) in pediatric total thyroidectomy (TT) patients., Methods: Patients <18 y undergoing TT between 2015 and 2021 were obtained from the National Surgical Quality Improvement Program-Pediatric database. Characteristics and outcomes were described and stratified by extent of node dissection. Temporal trends and predictors of PTAT were evaluated by multivariable logistic regression. Propensity score matching was used to compare PTAT clinical outcomes., Results: Among 2444 children (median age 14.9 y), 78% had thyroidectomy alone, 17% had thyroidectomy with central lymph node dissection, and 5% had thyroidectomy with modified radical neck dissection. Of the 150 patients who underwent PTAT, 62% were transplanted in the neck and 38% in the forearm. Overall, 0.6% had nerve injury/repair, 14% had prolonged postoperative hospitalization, and 0.9% was readmitted for hypocalcemia. Utilization of PTAT decreased over time. Predictors included adult general surgery/otolaryngology subspecialty (odds ratio 2.0, 95% confidence interval 1.3-3.2, P = 0.005) and extent of node dissection (odds ratio 3.2, 95% confidence interval 1.9-5.5, P < 0.0001). No significant differences in prolonged hospitalization (18% versus 13%, P = 0.10) or readmission for hypocalcemia (2.7% versus 1.1%, P = 0.23) were observed on propensity score matching., Conclusions: PTAT in pediatric TT is more commonly performed by adult subspecialty surgeons and in the setting of more extensive node dissections. PTAT utilization decreased over time. No significant differences in early postoperative outcomes were observed between cohorts. Further studies are needed to guide optimal parathyroid preservation strategies in children., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Human cytomegalovirus (CMV) causes a common congenital infection leading to long-term neurological impairments including brain, cochlear, and ocular pathology. Infection of newborn mice with murine (M)CMV is an established model of neuropathology caused by congenital CMV infection, with recent work suggesting that brain pathology may be driven by immune responses. In the eye, however, CMV retinitis is thought to result from virus-driven necrosis in the absence of T cell responses. We found that MCMV infection of newborn mice recapitulates human eye disease after congenital CMV infection, including focal chorioretinitis, inflamed vasculature, and disrupted blood-retinal barriers. Moreover, infection drove extensive T cell infiltration of the retina and marked gliosis. Blocking immune responses generally, or via targeting the chemokine receptor CXCR3, did not exacerbate retinal disease but instead prevented pathology despite retinal MCMV infection. Thus, our data establish this model for studies of congenital retinal disease and show that the immune system drives pathology in the neonatal eye after MCMV infection.

Purpose: Intercostal nerve cryoablation during minimally invasive repair of pectus excavatum (MIRPE) is an effective pain control technique. Some insurers may not reimburse for cryoablation in this context, contending that it's an experimental procedure. This study aimed to describe national trends in cryoablation use and evaluate outcomes and predictors of its use., Methods: The Pediatric Health Information System database was queried for pectus excavatum patients aged 9-21 who underwent MIRPE between 2016 and 2023. Concurrent cryoablation use was identified using billing/supply codes. Temporal trends in cryoablation utilization were described and quantified using linear regression. Demographics, resource utilization, and outcomes were compared for patients based on cryoablation utilization using chi-square and Kruskal-Wallis tests. Predictors of cryoablation use were evaluated with logistic regression., Results: This analysis included 2068 patients (mean age 15 ± 1.8 years; 86 % male). Cryoablation utilization increased from 33 % to 61 % from 2016 to 2023, with a strong positive trend (R 2  = 0.73). Cryoablation patients had fewer surgical complications (8 % vs 12 %, p = 0.004), shorter LOS (2.0 ± 1.3 vs. 2.8 ± 1.6 days, p < 0.001), fewer total mean opiate days billed (1.4 ± 1.1 vs. 1.6 ± 1.4 days, p < 0.0001) and higher total costs ($24,045 ± $9696 vs. $20,751 ± $9,237, p < 0.001). High-volume centers (odds ratio (OR) 1.9, 95 % confidence interval (CI) 1.2-3.0) and commercial HMO insurance (OR 2.7, 95 % CI 1.9-3.8) were predictors of cryoablation use., Conclusion: Cryoablation during MIRPE has increased nationally since 2016; now being performed in nearly two-thirds of all cases. Cryoablation should be considered a standard adjunct to MIRPE rather than an experimental technique., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Masticatory myositis (MM) is an inflammatory myopathy reported in dogs and is characterized by inflammation of the masticatory muscles (temporalis, masseter, and pterygoid muscles). Immunosuppressive therapy is the current recommended treatment for MM and may involve glucocorticoids, cyclosporine, azathioprine, mycophenolate mofetil, leflunomide, or a combination of these treatments that are slowly tapered to the lowest effective dose. However, side effects from multimodal medical therapy and complications associated with MM relapses have been reported. The purpose of this case series was to report oclacitinib as a treatment alternative to traditional medical management of MM. The intent of this alternative is to manage side effects from glucocorticoid use. Oclacitinib (1mg/kg per os q12h) was used solely for treatment of MM in three dogs. The dogs were followed up to >6 months after oclacitinib administration. An increase in oral range of motion, as determined by gape angle, was noted in all three dogs. However, a corresponding drop in antibody titers (2M fiber) did not occur. All dogs showed improvement in overall clinical management of MM, side effects from glucocorticoids, and clinical signs related to chronic prednisone use. Larger controlled trials with consistent measurements (interincisal distance, gape angle) and 2M fiber antibody titers are indicated to further assess validation of oclacitinib treatment of MM. The clinical outcome of all dogs was considered successful., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Energetic plasticizers are being sought for their use in energetic formulations when combined with explosives. An energetic plasticizer based on the insensitive highly explosive 3-amino-5-nitro-l,2,4-triazole (ANTA) was synthesized and characterized by spectroscopy, X-ray crystallography, thermal analyses, and safety testing. Lastly, density functional theory calculations were employed to examine the observed selectivity among the three nucleophilic ring nitrogen atoms of ANTA toward electrophiles such as ANTA acrylate; this selectivity was found to be a combination of steric, electronic, and hydrogen bonding effects.

Introduction: Patients with pectus excavatum (PE) often undergo cross-sectional imaging (CSI) to quantify severity for insurance authorization before surgical repair. The modified percent depth (MPD), an external caliper-based metric, was previously validated to be similar to the pectus index and correction index. This study explored family perceptions of CSI and MPD with respect to value and costs., Methods: This is a cross-sectional survey study including families of patients enrolled in an ongoing prospective multicenter study evaluating the use of MPD as an alternative to CSI for quantifying PE severity. Families of PE patients who underwent both MPD and CSI completed a survey to determine their perceptions of MPD and costs of CSI. Responses were described and associations were evaluated using chi squared, Wilcoxon rank-sum test and logistic regression as appropriate. Statistical significance was set to 0.05., Results: There were 136 surveys completed for a response rate of 88%. Respondents were confident in MPD (86%) and confident in its similarity to CSI (76%). Families of females were less confident in the measurements than males (55% versus 80%, P = 0.02; odds ratio 0.30 (0.11, 0.83). Obtaining CSI required time off work/school in 90% and a copay in 60%. Nearly half (49%) of respondents reported CSI was a time/financial hardship. Increasing copay led to decreased reassurance in CSI (55%: copay > $100 versus 77%: lower copay/75%: no copay; P = 0.04)., Conclusions: From the family perspective, MPD is valuable in assessing the severity of PE. Obtaining CSI was financially burdensome, particularly for those with higher copays. MPD measurements provide high value at low cost in assessing the severity of PE., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pediatric open tibial fractures represent a challenging subset of injuries with limited literature to guide management. For children, the epidemiology, management, and outcomes of tibial-shaft fractures have not been fully described., Methods: A retrospective analysis of the Trauma Quality Improvement Program Data Bank from 2017-2020 was used to query demographics, injury patterns, and management strategies in pediatric open tibial fractures. Fractures were compared by age group (0-5, 6-12, 13-17 years) and type (I/II vs type III). A subgroup analysis was performed on patients with type III open fractures., Results: A total of 3480 open tibial fractures were identified, 3049 were type I/II, and 431 were type III. Motor vehicle accidents (48%) were the most common mechanism of injury (P < 0.001). Subanalysis of 128 type IIIb/c tibial fractures revealed local flap reconstruction (25%) skin graft (25%), and free tissue transfer were the most common management strategies and soft-tissue coverage was achieved after 162 hours (interquartile range = 109-231). Negative pressure wound therapy was utilized in 63% of cases but used in isolation in only 23% of cases. Immediate fixation with intramedullary nailing was more frequently used in the 13-17 age group while plate fixation was more commonly used in younger age groups., Conclusions: Soft-tissue management patterns following open tibial shaft fractures mirror those seen in adult cohorts. The median time to achieve soft-tissue coverage exceeds the traditional 72-hour target advocated by Godina. Age-based variation is seen in orthopedic management of these fractures based on growth maintenance concerns., Competing Interests: Conflicts of interest and sources of funding: No financial discloses or conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Pediatric firearm injury prevention research in younger age groups is limited. This study evaluated a large multicenter cohort of younger children with firearm injuries, focusing on injury patterns and surgical resource utilization., Methods: Children ≤15 y old sustaining firearm injuries between 2016 and 2021 and treated at 10 pediatric trauma centers in Florida were included. Individual cases were reviewed for demographics, shooting details, injury patterns, resource utilization, and outcomes. Patients were grouped by age into preschool (0-5 y), elementary school (6-10 y), middle school (11-13 y), and early high school (14-15 y). Multivariable logistic regression was used to identify predictors of death and critical resource utilization., Results: A total of 489 children (80 preschool, 76 elementary school, 92 middle school, and 241 early high school) met inclusion criteria. Demographics, injury patterns, and resource utilization were similar across age groups. Assault and self-harm increased with age. Self-harm was implicated in 5% of cases but accounted for 18% of deaths. Hand surgery (i.e., below-elbow) procedures were common at 8%. Overall mortality was 10%, but markedly higher for self-harm injuries (47%). On multivariable regression, age and demographics were not predictive of death or critical resource utilization, but self-harm intent was a strong independent risk factor for both., Conclusions: This study suggests that given the age distribution and disproportionately high impact of self-harm injuries, behavioral health resources should be available to children at the middle school level or earlier. Hand surgery may represent an overlooked but frequently utilized resource to mitigate injury impact and optimize long-term function., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Child physical abuse (CPA) carries high risk of morbidity and mortality. Screening for CPA may be limited by subjective risk criteria and racial and socioeconomic biases. This study derived, validated, and compared age-stratified International Classification of Diseases, 10th revision (ICD-10) diagnosis codes indicating high risk of CPA., Methods: Injured children younger than 6 years from the Trauma Quality Improvement Program (TQIP) database were included; years 2017 to 2018 were used for derivation and 2019 for validation. Confirmed CPA was defined as a report of abuse plus discharge with alternate caregiver. Patients were classified as high vs. low CPA risk by three methods: (1) abuse-specific ICD-10 codes, (2) previously validated high-risk ICD-9 codes crosswalked to equivalent ICD-10 codes, and (3) empirically-derived ICD-10 codes from TQIP. These methods were compared with respect to sensitivity, specificity, area under the receiver-operator curve (AUROC), and uniformity across race and insurance strata., Results: A total of 122,867 children were included (81,347 derivation cohort, 41,520 validation cohort). Age-stratified high-risk diagnoses derived from TQIP consisted of 40 unique codes for ages 0 year to 2 years, 30 codes for ages 3 years to 4 years, and 20 codes for ages 5 years to 6 years. In the validation cohort, 890 children (2.1%) had confirmed CPA. On comparison with abuse-specific and crosswalked ICD-9 codes, TQIP-derived codes had the highest sensitivity (70% vs. 19% vs. 54%) and the highest AUROC (0.74 vs. 0.59 vs. 0.68, p < 0.0001) for confirmed abuse across all age groups. Age-based risk stratification using TQIP-derived codes demonstrated low variability by race (25% White vs. 25% Hispanic vs. 28% Black patients considered high-risk) and insurance status (23% privately insured vs. 26% uninsured)., Conclusion: High-risk CPA injury codes empirically derived from TQIP produced the best diagnostic characteristics and minimized some disparities. This approach, while requiring further validation, has the potential to improve CPA injury surveillance and decrease bias in screening protocols., Level of Evidence: Diagnostic Test/Criteria; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study evaluated observer variations in the interpretation of radiographic evidence for periodontal disease, tooth resorption, and endodontic disease in dogs. Forty dental radiographs were evaluated for 12 different parameters (periapical destruction of bone, wider than expected root canal, narrower than expected root canal, apical root resorption, loss of alveolar bone, external surface resorption, external replacement resorption, external inflammatory resorption, external cervical root resorption, internal surface resorption, internal replacement resorption, internal inflammatory resorption). Interpretations by 20 veterinary dentists, 10 veterinary dental residents, and 10 veterinary students were analyzed for consistency within groups and between groups by intraclass correlation coefficients (ICCs [95% CI]). Additionally, the agreement rate between groups compared to histopathological diagnosis, when available, and to a consensus group were evaluated. The results showed fair to good interobserver agreement for all participants when looking at all questions simultaneously (0.578 [0.515-0.635]) and with the consensus group (0.483 [0.451-0.517]). However, questions pertaining to various types of tooth resorption scored the lowest ICCs ranging from 0.005 (-0.311 to 0.321) to 0.189 (-0.105 to 0.402) across individual groups. Students had the lowest agreement compared to the consensus group for all questions (0.383 [0.347-0.421]) with fair to good agreement involving groups of residents (0.501 [0.465-0.538]), recently boarded diplomates (0.541 [0.506-0.578]), and more experienced diplomates (0.545 [0.510-0.582]). While dental radiographs are essential for clinical decision making, this study shows that interpretation of radiographs is highly subjective., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Bronchopulmonary dysplasia (BPD) is a common respiratory morbidity among premature infants. Nissen fundoplication may be performed on infants with BPD to protect the lungs from gastroesophageal reflux-related aspiration, but the indications and benefits associated with fundoplication are not well-defined. This study evaluated associations of Nissen with clinical outcomes in infants with severe BPD (sBPD), using propensity score matching to minimize bias and confounding., Methods: Infants ≤31 wk gestational age with sBPD (grade 2-3) admitted to a single neonatal intensive care unit (NICU) between January 2016 and October 2021 were included. Patients with sBPD who underwent Nissen fundoplication during initial NICU admission were propensity score-matched at a 1:2 ratio with control patients who did not undergo Nissen (no-Nissen). Outcomes were compared, including time to freedom from respiratory support (defined as ≤2 L nasal cannula), time to initial NICU discharge, and incidence of hospital readmission or death within 1 y postdischarge., Results: After propensity score matching, 18 Nissen infants were compared with 30 no-Nissen infants. The Nissen group trended toward longer time to freedom from respiratory support (median 105 versus 70 d, P = 0.09), and had longer initial hospital stays (188 versus 111 d, P = 0.002), more 1-y hospital readmissions (83% versus 50%, P = 0.04), and more tracheostomies (28% versus 0%, P = 0.005). Mortality during first-year postdischarge was similar (6% versus 10%, P = 1.0)., Conclusions: Despite adjustment for confounding variables, Nissen fundoplication was associated with prolonged support and greater resource utilization among infants with sBPD. Prospective studies are needed to clarify indications for fundoplication in this population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Golf carts (GCs) and all-terrain vehicles (ATVs) are popular forms of personal transport. Although ATVs are considered adventurous and dangerous, GCs are perceived to be safer. Anecdotal experience suggests increasing numbers of both GC and ATV injuries, as well as high severity of GC injuries in children. This multicenter study examined GC and ATV injuries and compared their injury patterns, resource utilization, and outcomes., Methods: Pediatric trauma centers in Florida submitted trauma registry patients age <16 years from January 2016 to June 2021. Patients with GC or ATV mechanisms were identified. Temporal trends were evaluated. Injury patterns, resource utilization, and outcomes for GCs and ATVs were compared. Intensive care unit admission and immediate surgery needs were compared using multivariable logistic regression., Results: We identified 179 GC and 496 ATV injuries from 10 trauma centers. GC and ATV injuries both increased during the study period (R 2 0.4286, 0.5946, respectively). GC patients were younger (median 11 vs 12 years, p=0.003) and had more intracranial injuries (34% vs 19%, p<0.0001). Overall Injury Severity Score (5 vs 5, p=0.27), intensive care unit (ICU) admission (20% vs 16%, p=0.24), immediate surgery (11% vs 11%, p=0.96), and mortality (1.7% vs 1.4%, p=0.72) were similar for GCs and ATVs, respectively. The risk of ICU admission (OR 1.19, 95% CI 0.74 to 1.93, p=0.47) and immediate surgery (OR 1.04, 95% CI 0.58 to 1.84, p=0.90) remained similar on multivariable logistic regression., Conclusions: During the study period, GC and ATV injuries increased. Despite their innocuous perception, GCs had a similar injury burden to ATVs. Heightened safety measures for GCs should be considered., Level of Evidence: III, prognostic/epidemiological., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Balanced blood product resuscitation with red blood cells, plasma, and platelets can be achieved using whole blood (WB) or component therapy (CT). However, balanced resuscitation of younger children with severe traumatic hemorrhage may be complicated by delays in delivering all blood components and concerns regarding multiple product exposures. We hypothesized that WB achieves balanced resuscitation faster than CT, with fewer product exposures and improved clinical outcomes., Methods: Children younger than 12 years receiving balanced resuscitation within 4 hours of arrival were identified from the 2017 to 2019 Trauma Quality Improvement Program database. Time to balanced resuscitation was defined as the time of initiation of WB or all three components. Patient characteristics, resuscitation details, and outcomes were compared between WB and CT groups. Time to balanced resuscitation was compared using Kaplan-Meier analysis and Cox regression modeling to adjust for covariates. Additional multivariable regression models compared number of transfusion exposures, intensive care unit (ICU) length of stay, and mortality., Results: There were 390 patients (109 WB, 281 CT) with median age 7 years, 12% penetrating mechanism, 42% severe traumatic brain injury, and 49% in-hospital mortality. Time to balanced resuscitation was shorter for WB versus CT (median, 28 vs. 87 minutes; hazard ratio [HR], 2.93; 95% confidence interval [CI], 2.31-3.72; p < 0.0001). Whole blood patients received fewer transfusion exposures (mean, 3.2 vs. 3.9; adjusted incidence rate ratio, 0.82; 95% CI, 0.72-0.92; p = 0.001) and lower total product volumes (50 vs. 85 mL/kg; p = 0.01). Intensive care unit stays trended shorter for WB versus CT (median, 10 vs. 12 days; adjusted HR, 1.32; 95% CI, 0.93-1.86), while in-hospital mortality was similar (50% vs. 45%; adjusted odds ratio, 1.11; 95% CI, 0.65-1.88)., Conclusion: In critically injured preadolescent children receiving emergent transfusion, WB was associated with faster time to balanced resuscitation, fewer transfusion exposures, lower blood product volumes, and a trend toward shorter ICU stays than CT., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pediatric trauma triage and transfer decisions should incorporate the likelihood that an injured child will require pediatric trauma center (PTC) resources. Resource utilization may be a better basis than mortality risk when evaluating pediatric injury severity. However, there is currently no consensus definition of PTC resource utilization that encompasses the full scope of PTC services., Methods: Consensus criteria were developed in collaboration with the Pediatric Trauma Society (PTS) Research Committee using a modified Delphi approach. An expert panel was recruited representing the following pediatric disciplines: prehospital care, emergency medicine, nursing, general surgery, neurosurgery, orthopedics, anesthesia, radiology, critical care, child abuse, and rehabilitation medicine. Resource utilization criteria were drafted from a comprehensive literature review, seeking to complete the following sentence: "Pediatric patients with traumatic injuries have used PTC resources if they..." Criteria were then refined and underwent three rounds of voting to achieve consensus. Consensus was defined as agreement of 75% or more panelists. Between the second and third voting rounds, broad feedback from attendees of the PTS annual meeting was obtained., Results: The Delphi panel consisted of 18 members from 15 institutions. Twenty initial draft criteria were developed based on literature review. These criteria dealt with airway interventions, vascular access, initial stabilization procedures, fluid resuscitation, blood product transfusion, abdominal trauma/solid organ injury management, intensive care monitoring, anesthesia/sedation, advanced imaging, radiologic interpretation, child abuse evaluation, and rehabilitative services. After refinement and panel voting, 14 criteria achieved the >75% consensus threshold. The final consensus criteria were reviewed and endorsed by the PTS Guidelines Committee., Conclusion: This study defines multidisciplinary consensus-based criteria for PTC resource utilization. These criteria are an important step toward developing a criterion standard, resource-based, pediatric injury severity metric. Such metrics can help optimize system-level pediatric trauma triage based on likelihood of requiring PTC resources., Level of Evidence: Diagnostic Test/Criteria; Level II., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To explore how university students' dietary intakes changed during COVID-19, and whether these changes differed by food security status., Participants: Six hundred students attending a New Jersey public university., Methods: A cross-sectional online survey asked about student intake. Food security status was measured using the 18-item US Household Food Security Survey. Open-ended questions were content analyzed and themes were compared between food secure (FS) and food insecure (FI) students., Results: The most frequently reported dietary changes for FI students were food source/sourcing (22.7%), food variety (19.7%), and food/meal properties (19.7%). For FS students, themes differed: no change (31.5%), food source/sourcing (31.3%), and health/nutrition (13.7%)., Conclusions: Students indicated dietary changes during the pandemic regardless of food security status, although FI students more frequently reported smaller, less healthy, and less varied meals. Colleges and universities can provide support through enhanced outreach and assistance during emergencies or extended periods of disruption.

The purpose of this study was to determine and compare the gape angles (temporomandibular joint range of motion with mouth opening) of conscious and anesthetized domestic felines and to compare gape angles with and without evidence of oral pain. This prospective study evaluated the gape angle of 58 domestic felines. The cats were grouped into painful ( n  = 33) and nonpainful cohorts ( n  = 25) and gape angles were compared during conscious and anesthetized conditions. Gape angles were determined based on measurements of the maximal interincisal distance and lengths of the mandible and maxilla followed by calculation of the law of cosines. The mean feline gape angle (standard deviation) was determined to be 45.3° (8.6 ° ) and 50.8 ° (6.2 ° ) for conscious and anesthetized felines respectively. There was no significant difference between painful and non-painful feline gape angles during conscious ( P  = .613) or anesthetized ( P  = .605) evaluations. There was a significant difference between anesthetized and conscious gape angles ( P  < .001) for both painful and non-painful cohorts. This study determined the standardized, normal feline temporomandibular joint (TMJ) gape angle in both conscious and anesthetized states. This study suggests that the feline gape angle is not a useful indicator of oral pain. By determining the feline gape angle, which was previously unknown, further evaluation of its utility as a non-invasive clinical parameter for evaluation of restrictive TMJ motions as well as its use for serial evaluations may be pursued., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Children experiencing physical abuse may initially present to hospitals with underappreciated minor injuries, only to experience more severe injuries in the future. The objectives of this study were to 1) describe young children presenting with high-risk diagnoses for physical abuse, 2) characterize the hospitals to which they initially presented, and 3) evaluate associations of initial presenting-hospital type with subsequent admission for injury., Methods: Patients aged younger than 6 years from the 2009-2014 Florida Agency for Healthcare Administration database with high-risk diagnoses (codes previously associated with >70% risk of child physical abuse) were included. Patients were categorized by the hospital type to which they initially presented: community hospital, adult/combined trauma center, or pediatric trauma center. Primary outcome was subsequent injury-related hospital admission within 1 year. Association of initial presenting-hospital type with outcome was evaluated with multivariable logistic regression, adjusting for demographics, socioeconomic status, preexisting comorbidities, and injury severity., Results: A total of 8626 high-risk children met inclusion criteria. Sixty-eight percent of high-risk children initially presented to community hospitals. At 1 year, 3% of high-risk children had experienced subsequent injury-related admission. On multivariable analysis, initial presentation to a community hospital was associated with higher risk of subsequent injury-related admission (odds ratio, 4.03 vs level 1/pediatric trauma center; 95% confidence interval, 1.83-8.86). Initial presentation to a level 2 adult or combined adult/pediatric trauma center was also associated with higher risk for subsequent injury-related admission (odds ratio, 3.19; 95% confidence interval, 1.40-7.27)., Conclusions: Most children at high risk for physical abuse initially present to community hospitals, not dedicated trauma centers. Children initially evaluated in high-level pediatric trauma centers had lower risk of subsequent injury-related admission. This unexplained variability suggests stronger collaboration is needed between community hospitals and regional pediatric trauma centers at the time of initial presentation to recognize and protect vulnerable children., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Relationships between social determinants of health and pediatric trauma mechanisms and outcomes are unclear in context of COVID-19., Methods: Children <16 years old injured between 2016 and 2021 from ten pediatric trauma centers in Florida were included. Patients were stratified by high vs. low Social Vulnerability Index (SVI). Injury mechanisms studied were child abuse, ATV/golf carts, and firearms. Mechanism incidence trends and mortality were evaluated by interrupted time series and multivariable logistic regression., Results: Of 19,319 children, 68% and 32% had high and low SVI, respectively. Child abuse increased across SVI strata and did not change with COVID. ATV/golf cart injuries increased after COVID among children with low SVI. Firearm injuries increased after COVID among children with high SVI. Mortality was predicted by injury mechanism, but was not independently associated with SVI, race, or COVID., Conclusion: Social vulnerability influences pediatric trauma mechanisms and COVID effects. Child abuse and firearm injuries should be targeted for prevention., Competing Interests: Declaration of competing interest There are no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To investigate and describe an extraoral approach to perform a maxillary nerve block in guinea pigs., Study Design: Prospective, randomized, blinded, descriptive, cadaveric study., Animals: A total of 14 adult guinea pig cadavers., Methods: Two cadavers were used for anatomic dissection and determination of maxillary nerve block approach. A maxillary nerve block via infraorbital approach was then performed in 12 cadavers. A low volume (0.1 mL) or high volume (0.2 mL) of diluted methylene blue injectate was randomly assigned to the right or left side, with the other volume used for the contralateral side. The maxillary nerve was dissected after each injection by an investigator blinded to injectate volume. The region of dye distribution was identified, and the degree of staining assigned an accuracy score (0-2). Nerve coverage was considered adequate if ≥6 mm of circumferential staining was present., Results: Accuracy evaluation indicated successful dye deposition in 10/12 [2 (0-2), median (range)] injections in the low volume group and 8/12 [2 (1-2)] injections in the high volume group. The majority (79.2%) of injections resulted in adequate nerve staining. There were no statistically significant differences between injectate volumes for accuracy (p = 0.64) or adequacy (p > 0.99) of staining., Conclusions: The infraorbital approach is a simple and practical method for maxillary nerve blockade in guinea pigs. An injectate volume of 0.1 mL results in adequate maxillary nerve coverage; however, additional studies are needed to assess the efficacy in clinical use., (Copyright © 2023 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aims to evaluate if there is any significant linguistic difference in LoR based on applicant's race/ethnicity., Design: Retrospective review of applications to pediatric surgery fellowship at a single institution (2016-2020). Race was self-reported by applicants. LoR were analyzed via the Linguistic Inquiry and Word Count (LIWC) software program., Setting: Johns Hopkins All Children's Hospital, St. Petersburg, Florida USA. A free-standing tertiary pediatric hospital., Participants: Pediatric surgery fellowship applicants from 2016 to 2020., Results: A total of 1086 LoR from 280 applicants (52% female) were analyzed. Racial distribution was Caucasians 62.1%, Asian 12.1%, Hispanics 7.1%, multiracial 6.4% African Americans 5%, and other/unknown 7.1%. Letter writers were largely male (84%), pediatric surgeons (63%) and professors (57%). There was no difference in LoR word count across races. LoR for female multiracial candidates contained higher use of affiliation and negative emotion terms compared to Hispanic females (p = 0.002 and 0.048, respectively), and past focus terms when compared to Caucasian and Asian female applicants (p < 0.001 and p = 0.003, respectively). Religion terms were more common in LoR for Asian females when compared to Caucasian females (p < 0.001)., Conclusion: This study demonstrates linguistic differences in LoR for pediatric surgery training programs based on applicant race/ethnicity. While differences are present, these do not suggest overt bias based on applicants race or ethnicity., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Insertable cardiac monitors are minimally invasive devices designed for implantation in the chest wall of patients to record heart rhythms and relate them to symptoms over prolonged periods. The Jot Dx™ (Abbott Laboratories, Abbott Park, IL, USA) is the latest Food and Drug Administration-cleared insertable cardiac monitor that is Bluetooth™ enabled allowing for near-immediate transmission of data from patients to physicians. We report on the first paediatric patient, in a patient weighing 11.7 kg, to undergo a modified, vertical, parasternal implantation of a Jot Dx™.

In religious philosophy, the concept of karma represents the effect of one's past and present actions on one's future. Macrophages are highly plastic cells with myriad roles in health and disease. In the setting of cancer, macrophages are among the most plentiful members of the immune microenvironment where they generally support tumor growth and restrain antitumor immunity. However, macrophages are not necessarily born bad. Macrophages or their immediate progenitors, monocytes, are induced to traffic to the tumor microenvironment (TME) and during this process they are polarized toward a tumor-promoting phenotype. Efforts to deplete or repolarize tumor-associated macrophages (TAM) for therapeutic benefit in cancer have to date disappointed. By contrast, genetic engineering of macrophages followed by their transit into the TME may allow these impressionable cells to mend their ways. In this review, we summarize and discuss recent advances in the genetic engineering of macrophages for the treatment of cancer., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

High nitrogen compounds find wide use in the development of new propellants and explosives as well as pharmaceutical chemistry as bioisosteres, bacterial stains, and antifungal agents. A class of underexplored high-nitrogen materials includes azidoximes and their 1-hydroxytetrazole isomers. Azidoximes possess an energetic azide group and are quite sensitive to impact, spark, and friction. Therefore, these materials are generated in situ and cyclized under mild acidic conditions to their 1-hydroxytetrazole isomers. Recently, we synthesized a novel 1,2,4-triazine-derived azidoxime; however, upon subjecting this material to established cyclization conditions, no reaction was observed, even after prolonged reaction times with heating. Additional 1,2,4-triazine-derived azidoximes also displayed a similar lack of reactivities. This observation led us to probe the reactivity of these materials with both a DFT investigation and crystallographically based electrostatic potential mapping. In all, the lack of reactivity toward cyclization was found to be due to an inability of 1,2,4-triazine-based azidoximes to isomerize into the reactive (E)-conformation, requiring an activation energy of 26.4 kcal mol -1 .

An energetic nitrate ester acrylate monomer ( 4 ) was synthesized in a total yield of 68% and polymerized to form the energetic nitrate ester acrylate polymer ( NEAP ). Compound 4 is a liquid at room temperature with a melting point of -8.6 °C and NEAP is a solid with a glass-transition temperature of -8.8 °C. Intermediates leading to 4 and NEAP were characterized by high-resolution mass spectrometry, elemental analysis, Fourier transform infrared spectroscopy, and proton and carbon nuclear magnetic resonance spectroscopies ( 1 H and 13 C{ 1 H} NMR). Both 4 and NEAP have electrostatic discharge, friction, and impact sensitivities comparable to those of trinitrotoluene, making NEAP a potential candidate for advanced energetic formulations., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

We derive the optimal funding mechanism to incentivize development and production of vaccines against diseases with epidemic potential. In the model, suppliers' costs are private information and investments are noncontractible, precluding cost-reimbursement contracts, requiring fixed-price contracts conditioned on delivery of a successful product. The high failure risk for individual vaccines calls for incentivizing multiple entrants, accomplished by the optimal mechanism, a (w+1)-price reverse Vickrey auction with reserve, where w is the number of selected entrants. Our analysis determines the optimal number of entrants and required funding level. Based on a distribution of supplier costs estimated from survey data, we simulate the optimal mechanism's performance in scenarios ranging from a small outbreak, causing harm in the millions of dollars, to the Covid-19 pandemic, causing harm in the trillions. We assess which mechanism features contribute most to its optimality., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Injured children with severe hemorrhage often receive blood product transfusions with ratios of plasma and platelets to packed red blood cells (PRBCs) approaching 1:1:1. Whether blood product ratios vary during pediatric resuscitation is unknown. This study (1) described precise timing of pediatric blood product administration, (2) characterized changes in blood product ratios over time, and (3) evaluated the association of blood products with early mortality while incorporating time-varying factors., Methods: Pediatric (younger than 18 years) trauma patients receiving high-volume transfusion (>40 mL/kg total products or >2 U PRBC or whole blood, during first 4 hours) were obtained from the 2017 to 2019 Trauma Quality Improvement Program database. The time of each individual product transfusion was recorded, along with demographics, injury details, and times of death. Patients were assigned to blood product groups at 15-minute intervals: high plasma/PRBC ratio (>1:1) with platelets, high plasma/PRBC ratio (>1:1) without platelets, low plasma/PRBC ratio (<1:1), PRBC only, and whole blood. Cox proportional hazards modeling for 24-hour mortality was performed, including blood product group as a time-varying variable and adjusting for relevant covariates., Results: Of 1,152 included patients (median age, 15 years; 32% penetrating, 28% severe traumatic brain injury [sTBI]), 18% died within 24 hours. During the resuscitation period, the number of patients in high-ratio groups increased over time, and patients switched blood product groups up to six times. There was no significant difference in mortality by blood product group. Among patients with sTBI, there was a strong trend toward lower mortality among high plasma/PRBC without platelets versus high plasma/PRBC with platelets (hazard ratio, 0.55; p = 0.07)., Conclusion: No significant association of high ratios or whole blood with mortality was seen when time-varying factors were incorporated. The impact of balanced resuscitation strategies, particularly platelet transfusion, may be greatest among patients with sTBI. Optimizing balanced resuscitation for children requires appropriately designed prospective studies., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Within a Hospital Medicine division at a large academic institution, an innovative program has been developed to offer third year medical learners enrolled in their Internal Medicine Clerkship the opportunity to deepen their diagnostic reasoning skills with a weekly case-based learning activity entitled "Hospital Medicine's Mystery Case of the Week". The mystery case curriculum has four primary learning objectives (1): To understand the value of employing a multisystem approach to a common presenting problem (2); To apply a diagnostic schema to a clinical problem (3); To apply knowledge of cost appropriate workups to a clinical case and (4) To identify cognitive biases that can influence decision making in the context of treating a clinical problem., Methods: A process evaluation of the mystery case curriculum was conducted over a 6-month implementation period. The process evaluation was guided by eight domains of focus: program acceptability, demand, implementation, practicality, adaptation, integration, expansion and limited-efficacy testing. Measures included a pre/post mixed-methods survey, attendance log and timesheet. Pre/post survey data was analyzed via paired samples t-tests and open-ended responses were analyzed via a deductive content analysis., Results: Process evaluation findings demonstrated the program had high levels of acceptability and demand. Survey findings suggest the curriculum may increase feelings of preparedness for Internal Medicine exams as well as student interest, comfort and confidence related to diagnostic processes., Conclusions: Future evaluations should work to understand the influence this curriculum has on diagnostic accuracy within a clinical setting., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

We sought to examine current practices and changes in practice regarding initial counseling for families of patients with hypoplastic left heart syndrome (HLHS) given the evolution of options and outcomes over time. Counseling (Norwood with Blalock-Taussig-Thomas shunt (NW-BTT), NW with right ventricle to pulmonary artery conduit (NW-RVPA), hybrid palliation, heart transplantation, or non-intervention/hospice (NI)) for patients with HLHS were queried via questionnaire of pediatric care professionals in 2021 and compared to identical questionnaire from 2011. Of 322 respondents in 2021 (39% female), 299 respondents were cardiologists (92.9%), 17cardiothoracic surgeons (5.3%), and 6 were nurse practitioners (1.9%). Respondents were largely from North America (96.9%). In 2021, NW-RVPA procedure was the preferred palliation for standard risk HLHS patient (61%) and was preferred across all US regions (p < 0.001). NI was offered as an option by 71.4% of respondents for standard risk patients and was the predominant strategy for patients with end-organ dysfunction, chromosomal abnormality, and prematurity (52%, 44%, and 45%, respectively). The hybrid procedure was preferred for low birth-weight infants (51%). In comparison to the identical 2011 questionnaire (n = 200), the NW-RVPA was endorsed more in 2021 (61% vs 52%, p = 0.04). For low birth-weight infants, hybrid procedure was more recommended than in 2011 (51% vs 21%, p < 0.001). The NW-RVPA operation is the most recommended strategy throughout the US for infants with HLHS. The hybrid procedure for low birth-weight infants is increasingly recommended. NI continues to be offered even in standard risk patients with HLHS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

3,4- and 3,5-Dinitropyrazoles (DNPs) were substituted with acryl and allyl groups on the N1 nitrogen atom, resulting in three novel energetic materials. These compounds are all liquids at room temperature with melting points ranging from -60.2 to -38.6 °C and were fully characterized by high-resolution mass spectrometry, elemental analysis, proton and carbon nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. These materials were also tested for electrostatic discharge, friction, and impact sensitivities and then compared to DNP starting materials and to the explosive nitroglycerin (NG). These results indicate that the synthesized compounds are less sensitive to impact compared to NG and have higher thermal stabilities to decomposition., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Genetically modified (GM) mice are essential tools in biomedical research. Traditional methods for generating GM mice are expensive and require specialized personnel and equipment. The use of clustered regularly interspaced short palindromic repeats (CRISPR) coupled with improved-Genome editing via Oviductal Nucleic Acids Delivery (i-GONAD) has highly increased the feasibility of producing GM mice in research laboratories. However, genetic modification in inbred mouse strains of interest such as C57BL/6 (B6) is still challenging because of their low fertility and embryo fragility. We have successfully generated multiple novel GM mouse strains in the B6 background while attempting to optimize i-GONAD. We found that i-GONAD reduced the litter size in superovulated pregnant females but did not impact pregnancy rates. Natural mating or low-hormone dose did not increase the low fertility rate observed in superovulated B6 females. However, diet enrichment had a positive effect on pregnancy success. We also optimized breeding conditions to increase the survival of small litters by co-housing i-GONAD-treated pregnant B6 females with synchronized pregnant FVB/NJ companion mothers. Thus, GM mice generation was increased by an enriched diet and shared pup rearing with highly fertile females such as FVB/NJ. In the present study, we generated 16 GM mice using a CRISPR/Cas system to target individual and multiple loci simultaneously or consecutively. We also compared homology-directed repair efficiency using different methods for LoxP insertion for conditional knockout mouse production. We found that a two-step serial LoxP insertion, in which each LoxP sequence was inserted individually in different i-GONAD procedures, was a low-risk high-efficiency method for generating floxed mice.

Objective: We analyzed the prevalence and type of bias in letters of recommendation (LOR) for pediatric surgical fellowship applications from 2016-2021 using natural language processing (NLP) at a quaternary care academic hospital., Design: Demographics were extracted from submitted applications. The Valence Aware Dictionary for sEntiment Reasoning (VADER) model was used to calculate polarity scores. The National Research Council dataset was used for emotion and intensity analysis.  The Kruskal-Wallis H-test was used to determine statistical significance.  SETTING: This study took place at a single, academic, free standing quaternary care children's hospital with an ACGME accredited pediatric surgery fellowship., Participants: Applicants to a single pediatric surgery fellowship were selected for this study from 2016 to 2021. A total of 182 individual applicants were included and 701 letters of recommendation were analyzed., Results: Black applicants had the highest mean polarity (most positive), while Hispanic applicants had the lowest.  Overall differences between polarity distributions were not statistically significant.   The intensity of emotions showed that differences in "anger" were statistically significant (p=0.03).  Mean polarity was higher for applicants that successfully matched in pediatric surgery., Discussion: This study identified differences in LORs based on racial and gender demographics submitted as part of pediatric surgical fellowship applications to a single training program. The presence of bias in letters of recommendation can lead to inequities in demographics to a given program. While difficult to detect for humans, natural language processing is able to detect bias as well as differences in polarity and emotional intensity. While the types of emotions identified in this study are highly similar among race and gender groups, the intensity of these emotions revealed differences, with "anger" being most significant., Conclusion: From this work, it can be concluded that bias in LORs, as reflected as differences in polarity, which is likely a result of the intensity of the emotions being used and not the types of emotions being expressed.   Natural language processing shows promise in identification of subtle areas of bias that may influence an individual's likelihood of successful matching., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Explosives exist in and are expected to withstand a variety of harsh environments up to and including ionizing radiation, though little is known about the chemical consequences of exposing explosives to an ionizing radiation field. This study focused on the radiation-induced chemical changes to a variety of common energetic functional groups by utilizing a consistent molecular backbone. Dodecane was substituted with azide, nitro, nitrate ester, and nitramine functional groups and γ-irradiated with 60 Co in order to study how the functional group degraded along with what the relative stability to ionizing radiation was. Chemical changes were assessed using a combination of analysis techniques including: nuclear magnetic resonance (NMR) spectroscopy, gas chromatography of both the condensed and gas phases, Raman spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. Results revealed that much of the damage to the molecules was on the energetic functional group and often concentrated on the trigger linkage, also known as the weakest bond in the molecule. The general trend from most to least susceptible to radiolytic damage was found to be D-ONO 2 → D-N 3 → D-NHNO 2 → D-NO 2 . These results also appear to be in line with the relative stability of these functional groups to things such as photolysis, thermolysis, and explosive insults., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Implantable cardiac monitors (ICM) allow for symptom-rhythm correlation. Current manufacturer recommendations call for implantation of ICMs diagonally in the left anterior chest. Complications such as skin tenting and device erosion have occurred using this technique in pediatric patients. The purpose of this study was to assess the safety and efficacy of implanting ICMs via new vertical-parasternal technique (VP) compared to manufacturer-recommended diagonal technique (D) in pediatric patients. Single-center, IRB-approved retrospective study of pediatric patients that underwent ICM implantation from 01/01/2017 to 12/01/2021. All implants were performed after informed consent, under sterile conditions in the electrophysiology laboratory. Data collected included demographics, implant orientation (VP or D), complications, device type, presence of P-wave, and measurement of R-wave amplitude at implantation and follow-up. ICMs were implanted in 34 patients without congenital heart disease. Initial R-wave amplitude average for VP 1.00, D 0.99 (p = NS). Follow-up R-wave amplitude was 0.97 VP and 0.93 for D (p = NS). Median follow-up period for VP was 11 and for D was 20 months (p = NS). D cohort had only post-procedural complication due to skin tenting of the ICM in child < 2.5 years of age. No skin tenting, erosions, or complications occurred in the vertical-parasternal implant technique. Vertical-Parasternal ICM implantation is as safe and effective as the manufacturer-recommended diagonal implant. Short- and long-term data demonstrate an equivalent R-wave detection and no significant signal deterioration, even in very young children. No skin tenting, erosions, or complications occurred in the vertical parasternal implant technique., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Total thyroidectomy (TT) in children is performed by pediatric general surgeons (P-GS), pediatric otolaryngologists (P-ENT), or adult GS/ENT. This study evaluated short-term pediatric TT outcomes, focusing on surgical subspecialties., Methods: Pediatric (<18 years) TT with/without central limited lymph node dissection (CLND) between 2015 and 2020 were obtained from the National Surgical Quality Improvement Program-Pediatric database. Risk factors for prolonged hospitalization (PH,>2 days) and 30-day readmission were investigated with multivariate logistic regression., Results: Of 1535 patients, 14% had PH and 2% were readmitted. PH rates for P-ENT vs. P-GS vs. adult were 21% vs. 11% vs. 10%, respectively. Adjusted risk of PH was higher for P-ENT (OR 1.70, p = 0.003) but similar for P-GS/adult. There was no difference for risk of readmission by subspecialty., Conclusion: PH is more likely after pediatric TT performed by P-ENT, as compared to P-GS or adult surgeons. While TT may be performed safely by individual subspecialties, collaboration across specialties may further optimize outcomes., Competing Interests: Declaration of competing interest No authors have any conflict of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In Goodkin-Gold et al. (2021), we analyzed optimal subsidies for a vaccine against an epidemic outbreak like Covid-19. This companion paper alters the underlying epidemiological model to suit endemic diseases requiring continuous vaccination of new cohorts-also suiting an epidemic like Covid-19 if, following Gans (2020), one assumes peaks are leveled by social distancing. We obtain qualitatively similar results: across market structures ranging from perfect competition to monopoly, the subsidy needed to induce first-best vaccination coverage on the private market is highest for moderately infectious diseases, which invite the most free riding; extremely infectious diseases drive more consumers to become vaccinated, attenuating externalities. Stylized calibrations to HIV, among other diseases, suggest that first-best subsidies can be exorbitantly high when suppliers have market power, rationalizing alternative policies observed in practice such as bulk purchases negotiated by the government on behalf of the consumers., (© 2022 The Author(s).)

Simulation offers multiple tools that apply to medical settings, but little is known about the application of simulation to pediatric trauma workflow changes. Our institution recently underwent significant clinical changes in becoming an independent pediatric trauma center. We used a simulation-based clinical systems testing (SbCST) approach to manage change-associated risks. The purpose of this study was to describe our SbCST process, evaluate its impact on patient safety, and estimate financial costs and benefits., Methods: SbCST consisted of the following steps: (1) change-based needs assessment, in which stakeholders developed relevant simulation scenarios; (2) scenario implementation; and (3) postsimulation failure mode and effects analysis (FMEA) to identify latent safety threats (LSTs). LSTs were prioritized for mitigation based on the expected probability and severity of adverse event occurrences. We calculated the costs associated with the simulation process. We conservatively estimated SbCST cost savings using 3 approaches: (1) FMEA-based avoidance of adverse events; (2) avoidance of trauma readmissions; and (3) avoidance of medical liability lawsuits., Results: We implemented 2 simulation scenarios prechange. FMEA revealed 49 LSTs, of which 9 were highest priority (catastrophic severity and high likelihood of occurrence). These were prioritized and mitigated using the hospital's quality/safety framework. Cost-benefit analysis based on FMEA event avoidance demonstrated net cost savings to the institution ranging from $52,000-227,000 over the 3-month postchange period. Readmission-based and liability-based estimates also produced favorable results., Conclusions: The SbCST approach identified multiple high-impact safety risks and financially benefited the institution in managing significant pediatric trauma clinical process changes., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Until now, it has been assumed that the primary decomposition pathway for the liquid plasticizer bis(2,2-dinitropropyl)acetal and bis(2,2-dinitropropyl)formal (BDNPA/F) was nitrous acid elimination (NAE). An ultrahigh-performance liquid chromatography (UHPLC) coupled to quadrupole time-of-flight mass spectrometry (QTOF) methodology was developed to discover and identify the degradation products of BDNPA/F. No evidence of NAE was found. However, two other degradation pathways were found: (1) hydrolysis of the acetal/formal functional group and (2) radical-based homolysis of the C-N bond, followed by hydrogen atom abstraction. Hydrolysis of BDNPA/F proceeds by the formation of 2,2-dinitropropanol (DNPOH) and 2,2-dinitropropyl hemiacetal/hemiformal, which further decompose into DNPOH and ethanal/methanal, respectively. Hydrolysis is the dominant decomposition pathway in all samples; however, at higher temperatures, C-N homolysis becomes more significant. Also, the solid PBX 9501 has different ratios of decomposition products than the liquid BDNPA/F due to the slower rate of diffusion through solids than liquids., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Context: Sedentary behavior and inability to participate in organized physical activity has negatively affected the physical and mental health of children and adolescents; however, cardiac injury and associated risk for sudden cardiac death with return to activity remains a major concern. Guidelines have been proposed for return to activities; however, these fail to address the needs of younger children and those participating in more casual activities. Guidance is needed for primary care providers to facilitate safe return to everyday activity and sports and to help direct appropriate laboratory, electrocardiographic, and anatomical assessment., Evidence Acquisition: Review of computerized databases of available literature on SARS-CoV-2 infection in children and postinfection sequelae, risk factors for sudden cardiac death, and previous return to play recommendations., Study Design: Clinical guidelines based on available evidence and expert consensus., Level of Evidence: Level 4., Results: In this report, we review the literature on return to activity after SARS-CoV-2 infection and propose recommendations for cardiac clearance for children and adolescents. Though severe disease and cardiac injury is less common in children than in adults, it can occur. Several diagnostic modalities such as electrocardiography, echocardiography, cardiac magnetic resonance imaging, and serologic testing may be useful in the cardiac evaluation of children after SARS-CoV-2 infection., Conclusion: Gradual return to activity is possible in most children and adolescents after SARS-CoV-2 infection and many of these patients can be cleared by their primary care providers. Providing education on surveillance for cardiopulmonary symptoms with return to sports can avoid unnecessary testing and delays in clearance.

Background/purpose: Resource-based severity of injury (SOI) measures, such as the International Classification of Disease (ICD) Critical Care Severity Score (ICASS), may characterize traumatic burden better than standard mortality-based measures. The purpose of this study was to validate the ICASS in a representative national-level trauma cohort and compare SOI measures between children and adults., Methods: The National Trauma Databank was used to derive (2008-12) and validate (2013-15) ICASS and ICD Injury Severity Scores (ICISS, standard mortality-based SOI measure). SOI metrics and outcomes were compared between pediatric, adult, and elderly age groups. Logistic regression modeling evaluated predictors of critical care resource utilization., Results: Derivation and validation cohorts consisted of 3.90 and 1.97 million patients, respectively. ICASS strongly predicted actual critical care utilization (OR 1.04, 95% CI 1.04-1.04, p<0.0001). Mean ICASS was 24.4 for children and 33.0 for adults (ratio 0.74), indicating predicted critical care utilization in children was three-quarters that of adults. In contrast, predicted pediatric mortality was less than half that of adults., Conclusions: Mortality-based SOI measures underestimate pediatric burden of injury. This study validates ICASS and demonstrates that pediatric resource-based SOI is more similar to that of adults. ICASS is easily calculated without a trauma registry and complements mortality-based measures. Level of evidence III, retrospective comparative study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Phrenic nerve injury can lead to a disruption of the autonomic nervous system (ANS) resulting in episodes of bradycardic arrest. Implanted diaphragmatic pacing has been used to overcome phrenic nerve paralysis, but these do not change the ANS. Therefore, patients with phrenic nerve paralysis may require the implantation of a permanent cardiac pacemaker to overcome bradycardic episodes. Having two electronic devices in the same patient may lead to device-device interaction (DDI). This can result in over-sensing leading to lack of pacing of either device. We present the case of a 17-year-old pediatric male with phrenic nerve injury who required implantation of both diaphragm and cardiac pacemaker. Intra-procedural interrogation of the cardiac pacemaker demonstrated DDI in unipolar mode, but not in bipolar. Thus, we demonstrated the safe utilization of multiple implantable electronic devices in the pediatric patient without device-device interaction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Our prospective study analyzed clinical, radiographic, and histological characteristics of 102 intrinsically stained teeth. Sixty-nine dogs ranging from one to fifteen years of age were included in this study. Little more than half of the intrinsically stained teeth had no evidence of coronal injury (53.9%, 55/102). We found that most intrinsically stained teeth were histologically nonvital (87.6%, 85/97) and approximately 2/3 of these (57.7%, 56/97) had no histological endodontic or periodontal inflammation at the time of evaluation. Radiographic evidence of endodontic disease was present in 57% (58/102) of the intrinsically stained teeth. Radiographic evidence of periodontal disease was present in 48% (49/102) of intrinsically stained teeth and 28% (29/102) had radiographic evidence of tooth resorption. 18.6% (19/102) of intrinsically stained teeth were radiographically normal. Evidence of pulp necrosis was common in these intrinsically stained teeth, while only occasional teeth (12.4%, 12/97) had histologically confirmed pulpitis. All teeth with radiographic evidence of periapical lucency had pulp necrosis. Based on our histological findings, the majority of intrinsically stained teeth 87.6% are truly nonvital.

Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half or even quarter doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggests strong interest in these approaches., Competing Interests: Competing interest statement: W.W. provides scientific consultancy for Certara, a drug development company, and 1 Day Sooner, a COVID-19 human challenge trial advocacy group. W.W. reports no material conflicts of interest with regards to development of COVID-19 vaccines., (Copyright © 2022 the Author(s). Published by PNAS.)

Maxillofacial trauma is a common presentation in veterinary medical practice. Accurate assessment, diagnostics, pain management, and finally repair are tenants to treatment. In addition to typical tenants for fracture repair, the restoration of occlusion and return to function (eating, drinking, grooming) are unique to trauma management in these patients. Options for repair include conservative management (tape muzzles), noninvasive repair techniques (interdental wiring and composite splinting), and invasive repair techniques (interfragmentary wiring and plate and screw fixation)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Radiofrequency ablation (RFA) is commonly used to treat atrial fibrillation (AF). However, the outcome is often compromised due to the lack of direct real-time feedback to assess lesion transmurality. In this work, we evaluated the ability of polarization-sensitive optical coherence tomography (PSOCT) to measure cardiac wall thickness and assess RF lesion transmurality during left atrium (LA) RFA procedures. Quantitative transmural lesion criteria using PSOCT images were determined ex vivo using an integrated PSOCT-RFA catheter and fresh swine hearts. LA wall thickness of living swine was measured with PSOCT and validated with a micrometer after harvesting the heart. A total of 38 point lesions were created in the LA of 5 living swine with the integrated PSOCT-RFA catheter using standard clinical RFA procedures. For all lesions with analyzable PSOCT images, lesion transmurality was assessed with a sensitivity of 89% (17 of 19 tested positive) and a specificity of 100% (5 of 5 tested negative) using the quantitative transmural criteria. This is the first report of using PSOCT to assess LA RFA lesion transmurality in vivo. The results indicate that PSOCT may potentially provide direct real-time feedback for LA wall thickness and lesion transmurality., (© 2021. The Author(s).)