Impact of institutional prophylaxis guidelines on rates of pediatric venous thromboembolism following trauma-A multicenter study from the pediatric trauma society research committee.

BACKGROUND: A paucity of data exists with regard to the incidence, management, and outcomes of venous thromboembolism (VTE) in injured children. We sought to determine the impact of institutional chemoprophylaxis guidelines on VTE rates in a pediatric trauma population. METHODS: A retrospective review of injured children (≤15 years) admitted between 2009 and 2018 at 10 pediatric trauma centers was performed. Data were gathered from institutional trauma registries and dedicated chart review. The institutions were surveyed as to whether they had chemoprophylaxis guidelines in place for high-risk pediatric trauma patients, and outcomes were compared based on the presence of guidelines using χ 2 analysis ( p < 0.05). RESULTS: There were 45,202 patients evaluated during the study period. Three institutions (28,359 patients, 63%) had established chemoprophylaxis policies during the study period ("Guidelines"); the other seven centers (16,843 patients, 37%) had no such guidelines ("Standard"). There were significantly lower rates of VTE in the Guidelines group, but these patients also had significantly fewer risk factors. Among critically injured children with similar clinical presentations, there was no difference in VTE rate. Specifically within the Guidelines group, 30 children developed VTE. The majority (17/30) were actually not indicated for chemoprophylaxis based on institutional guidelines. Still, despite protocols only one VTE patient in the guidelines group who was indicated for intervention ended up receiving chemoprophylaxis prior to diagnosis. No consistent ultrasound screening protocol was in place at any institution during the study. CONCLUSION: The presence of an institutional policy to guide chemoprophylaxis for injured children is associated with a decreased overall frequency of VTE, but this disappears when controlling for patient factors. However, the overall efficacy is impacted by a combination of deficits in guideline compliance and structure. Further prospective data are needed to help determine the ideal role for chemoprophylaxis and protocols in pediatric trauma. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Pediatric Trauma Care Standardization: A Statewide Survey of Trauma Providers and Program Managers.

INTRODUCTION: Rural-urban disparities in pediatric trauma outcomes are well documented. However, few studies examine how differences in setting and resources impact rural providers' approach to trauma. We sought to understand the provider experience in managing injured children across our state and assess the potential for standardization of care. METHODS: A statewide cross-sectional survey was distributed to trauma providers and program managers through the American College of Surgeons, the Oregon Medical Board lists, and the State Trauma Advisory Board. Topics included pediatric management processes, challenges, and transfer or admission procedures. Rural-urban commuting codes were used to categorize responses. RESULTS: Of the 350 individuals who sent the survey, 68 responded (response rate 19%), representing 67% of trauma-verified hospitals and 72% of Oregon counties. Fifty-six respondents (82%) care for injured children, with 58% practicing rurally and 22% at critical access hospitals. Rural providers experienced lower trauma volumes (<1 patient/month, 63% versus 0%, P < 0.001), more difficulties obtaining pediatric-appropriate material resources (44% versus 30%), and challenges caring for infants/toddlers (25% versus 17%). Despite 77% of rural providers stating that <10% of patients had multisystem injuries, they described using full-body CT often (41% versus 10%, P = 0.007). Transfer interruptions were common (93%), with 44% having cancelled a transfer. The majority supported admission/transfer (85%) and imaging (82%) protocols. CONCLUSIONS: Rural providers experience lower pediatric trauma volumes, greater material-resource issues, and discomfort with traumatically injured small children. Lack of care standardization may lead to reliance on full-body CT, and potentially complex/avoidable transfers. Adoption of standardized protocols could facilitate a state-wide collaborative approach to pediatric trauma management.

Venous thromboembolic screening in pediatric trauma: A prospective cohort study of risk-stratified ultrasonography.

BACKGROUND: This prospective observational cohort study evaluates risk-stratified venous thromboembolism (VTE) screening in injured children. While the reported incidence of VTE is 6% to 10% among critically injured children, there is no standard for screening. Venous thromboembolism may have long-term sequelae in children, including postthrombotic syndrome. METHODS: Patients admitted to a level 1 pediatric trauma center were risk stratified for VTE using a validated prediction algorithm. Children at high risk (risk scores ≥523; i.e., ≥1% risk) received screening duplex ultrasonography. Children at moderate risk (risk scores 410-522; i.e., 0.3-0.99% risk) were screened as a comparison/control. RESULTS: Three-hundred fifty-five children were consecutively risk stratified from October 2019 to May 2021. Forty-seven children received screening duplex ultrasounds: 21 from a high-risk cohort and 26 from a moderate-risk cohort. Four children were diagnosed with VTE in the high-risk cohort compared with seven in the moderate-risk cohort ( p = 0.53). Total incidence of VTE among screened children was 23.4% (11 of 47). Asymptomatic VTE accounted for 81.8% of all events (9 of 11). Fifty-four percent (6 of 11) of VTE were central venous catheter associated. Venous thromboembolism in surviving children resolved by 3 to 6 months with no symptoms of postthrombotic syndrome after 1 year. No cases of VTE were identified in unscreened children, yielding an institutional VTE incidence of 3.1% (11 of 355). DISCUSSION: Risk-stratified screening demonstrates a significant incidence of asymptomatic VTE in injured children. These results may guide reevaluation of prediction algorithms developed from symptomatic VTE risk and longitudinal study of the sequelae of asymptomatic VTE. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Non-melanoma skin cancer segmentation for histopathology dataset.

Densely labelled segmentation data for digital pathology images is costly to produce but is invaluable to training effective machine learning models. We make available 290 hand-annotated histopathology tissue sections of the 3 most common skin cancers; basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC). These non-melanoma skin cancers constitute over 90% of all skin cancer diagnoses and hence this dataset gives an opportunity to the scientific community to benchmark analytic methodologies on a significant portion of the dermatopathology workflow. The data represents typical cases of the three cancer types (not requiring a differential diagnosis) across shave, punch and excision biopsy contexts. Each image is accompanied with a segmentation mask which characterizes the section into 12 tissue types, specifically: keratin, epidermis, papillary dermis, reticular dermis, hypodermis, inflammation, glands, hair follicles and background, as well as BCC, SCC and IEC. Included also are cancer margin measurements to work towards automated assessment of surgical margin clearance and tumour invasion. This leaves open many opportunities for researchers to utilize or extend the dataset, building upon recent work on image analysis problems in skin cancer (Thomas et al., 2021).

Protect Our Kids: a novel program bringing hemorrhage control to schools.

BACKGROUND: Following the shooting at Sandy Hook Elementary School, the Hartford Consensus produced the Stop the Bleed program to train bystanders in hemorrhage control. In our region, the police bureau delivers critical incident training to public schools, offering instruction in responding to violent or dangerous situations. Until now, widespread training in hemorrhage control has been lacking. Our group developed, implemented and evaluated a novel program integrating hemorrhage control into critical incident training for school staff in order to blunt the impact of mass casualty events on children. METHODS: The staff of 25 elementary and middle schools attended a 90-minute course incorporating Stop the Bleed into the critical incident training curriculum, delivered on-site by police officers, nurses and doctors over a three-day period. The joint program was named Protect Our Kids. At the conclusion of the course, hemorrhage control kits and educational materials were provided and a four-question survey to assess the quality of training using a ten-point Likert scale was completed by participants and trainers. RESULTS: One thousand eighteen educators underwent training. A majority were teachers (78.2%), followed by para-educators (5.8%), counselors (4.4%) and principals (2%). Widely covered by local and state media, the Protect Our Kids program was rated as excellent and effective by a majority of trainees and all trainers rated the program as excellent. CONCLUSIONS: Through collaboration between trauma centers, police and school systems, a large-scale training program for hemorrhage control and critical incident response can be effectively delivered to schools.

LLAMA: a robust and scalable machine learning pipeline for analysis of large scale 4D microscopy data: analysis of cell ruffles and filopodia.

BACKGROUND: With recent advances in microscopy, recordings of cell behaviour can result in terabyte-size datasets. The lattice light sheet microscope (LLSM) images cells at high speed and high 3D resolution, accumulating data at 100 frames/second over hours, presenting a major challenge for interrogating these datasets. The surfaces of vertebrate cells can rapidly deform to create projections that interact with the microenvironment. Such surface projections include spike-like filopodia and wave-like ruffles on the surface of macrophages as they engage in immune surveillance. LLSM imaging has provided new insights into the complex surface behaviours of immune cells, including revealing new types of ruffles. However, full use of these data requires systematic and quantitative analysis of thousands of projections over hundreds of time steps, and an effective system for analysis of individual structures at this scale requires efficient and robust methods with minimal user intervention. RESULTS: We present LLAMA, a platform to enable systematic analysis of terabyte-scale 4D microscopy datasets. We use a machine learning method for semantic segmentation, followed by a robust and configurable object separation and tracking algorithm, generating detailed object level statistics. Our system is designed to run on high-performance computing to achieve high throughput, with outputs suitable for visualisation and statistical analysis. Advanced visualisation is a key element of LLAMA: we provide a specialised tool which supports interactive quality control, optimisation, and output visualisation processes to complement the processing pipeline. LLAMA is demonstrated in an analysis of macrophage surface projections, in which it is used to i) discriminate ruffles induced by lipopolysaccharide (LPS) and macrophage colony stimulating factor (CSF-1) and ii) determine the autonomy of ruffle morphologies. CONCLUSIONS: LLAMA provides an effective open source tool for running a cell microscopy analysis pipeline based on semantic segmentation, object analysis and tracking. Detailed numerical and visual outputs enable effective statistical analysis, identifying distinct patterns of increased activity under the two interventions considered in our example analysis. Our system provides the capacity to screen large datasets for specific structural configurations. LLAMA identified distinct features of LPS and CSF-1 induced ruffles and it identified a continuity of behaviour between tent pole ruffling, wave-like ruffling and filopodia deployment.

Venous thromboembolic risk stratification in pediatric trauma: A Pediatric Trauma Society Research Committee multicenter analysis.

BACKGROUND: Venous thromboembolism (VTE) in injured children is rare, but its consequences are significant. Several risk stratification algorithms for VTE in pediatric trauma exist with little consensus, and all are hindered in development by relying on registry data with known inaccuracies. We performed a multicenter review to evaluate trauma registry fidelity and confirm the effectiveness of one established algorithm across diverse centers. METHODS: Local trauma registries at 10 institutions were queried for all patients younger than 18 years admitted between 2009 and 2018. Additional chart review was performed on all "VTE" cases and random non-VTE controls to assess registry errors. Corrected data were then applied to our prediction algorithm using 10 real-time variables (Glasgow Coma Scale, age, sex, intensive care unit admission, transfusion, central line placement, lower extremity/pelvic fracture, major surgery) to calculate VTE risk scores. Contingency table classifiers and the area under a receiver operator characteristic curve were calculated. RESULTS: Registries identified 52,524 pediatric trauma patients with 99 episodes of VTE; however, chart review found that 13 cases were misclassified for a corrected total of 86 cases (0.16%). After correction, the algorithm still displayed strong performance in discriminating VTE-fated encounters (sensitivity, 69%; area under the receiver operating characteristic curve, 0.96). Furthermore, despite wide institutional variability in VTE rates (0.04-1.7%), the algorithm maintained a specificity of >91% and a negative predictive value of >99.7% across centers. Chart review also revealed that 54% (n = 45) of VTEs were directly associated with a central line, usually femoral (n = 34, p < 0.001 compared with upper extremity), and that prophylaxis rates were underreported in the registries by about 50%; still, only 19% of the VTE cases had been on prophylaxis before diagnosis. CONCLUSION: The VTE prediction algorithm performed well when applied retrospectively across 10 diverse pediatric centers using corrected registry data. These findings can advance initiatives for VTE screening/prophylaxis guidance following pediatric trauma and warrant prospective study. LEVEL OF EVIDENCE: Clinical decision rule evaluated in a single population, level III.

Interpretable deep learning systems for multi-class segmentation and classification of non-melanoma skin cancer.

We apply for the first-time interpretable deep learning methods simultaneously to the most common skin cancers (basal cell carcinoma, squamous cell carcinoma and intraepidermal carcinoma) in a histological setting. As these three cancer types constitute more than 90% of diagnoses, we demonstrate that the majority of dermatopathology work is amenable to automatic machine analysis. A major feature of this work is characterising the tissue by classifying it into 12 meaningful dermatological classes, including hair follicles, sweat glands as well as identifying the well-defined stratified layers of the skin. These provide highly interpretable outputs as the network is trained to represent the problem domain in the same way a pathologist would. While this enables a high accuracy of whole image classification (93.6-97.9%), by characterising the full context of the tissue we can also work towards performing routine pathologist tasks, for instance, orientating sections and automatically assessing and measuring surgical margins. This work seeks to inform ways in which future computer aided diagnosis systems could be applied usefully in a clinical setting with human interpretable outcomes.

Significant practice variability exists in the prevention of venous thromboembolism in injured children: results from a joint survey of the Pediatric Trauma Society and the Trauma Center Association of America.

BACKGROUND/PURPOSE: The purpose of this study was to characterize current practices to prevent venous thromboembolism (VTE) in children and measure adherence to recent joint consensus guidelines from the Pediatric Trauma Society and Eastern Association for the Surgery of Trauma (PTS/EAST). METHODS: An 18-question survey was sent to the membership of PTS and the Trauma Center Association of American. Responses were compared with Chi-square test. RESULTS: One hundred twenty-nine members completed the survey. Most respondents were from academic (84.5%), Level 1 pediatric (62.0%) trauma centers. Criteria for VTE prophylaxis varied between hospitals with freestanding pediatric trauma centers significantly more likely to stratify children by risk factors than adult trauma centers (p = 0.020). While awareness of PTS/EAST guidelines (58.7% overall) was not statistically different between hospital types (44% freestanding adult, 52% freestanding pediatric, 71% combined adult pediatric, p = 0.131), self-reported adherence to these guidelines was uniformly low at 37.2% for all respondents. Lastly, in three clinical scenarios, respondents chose VTE screening and prophylaxis plans in accordance with a prospective application of PTS/EAST guidelines 55.0% correctly. CONCLUSION: Currently no consensus regarding the prevention of VTE in pediatric trauma exists. Prospective application of PTS/EAST guidelines has been limited, likely due to poor quality of evidence and a reliance on post-injury metrics. Results of this survey suggest that further investigation is needed to more clearly define the risk of VTE in children, evaluate, and prospectively validate alternative scoring systems for VTE prevention in injured children. LEVEL OF EVIDENCE: N/A-Survey.

Contemporary postoperative imaging practices among pediatric surgeons for image-guided central venous line placement: A survey of the American Pediatric Surgical Association.

BACKGROUND/PURPOSE: Rare life-threatening complications after central venous line (CVL) placement in children may encourage the routine use of postoperative imaging, despite multiple studies demonstrating the limited utility of this practice. The aim of this study was to investigate the nature of this discordance. METHODS: A 10-question survey was sent to 1,239 members of the American Pediatric Surgical Association (APSA) addressing contemporary practices regarding CVL placement and postoperative imaging. RESULTS: Five hundred eighteen (42%) surveys were completed. The majority of respondents routinely obtain a chest radiograph (CXR) after image-guided CVL placement (52%). Years in practice, operative volume, and practice type were not statistically associated with postoperative CXR usage (all p > 0.05). 'Routine' users were more likely to cite "standard of care" (p < 0.001), position verification (p < 0.001), and complication identification (p < 0.001) as indications for use than those who use CXR selectively. CONCLUSION: Routine use of postoperative CXR after image-guided CVL placement remains common among pediatric surgeons. Significant variation exists in the indication for this study, with considerable disagreement between 'selective' and 'routine' users. Consideration should be given for an APSA standardized guideline utilizing a clinically-driven approach to CVL placement and postoperative imaging to align with evidence-based practice. LEVEL OF EVIDENCE: N/A - descriptive analysis of survey results.

Validation of a venous thromboembolism prediction algorithm for pediatric trauma: A national trauma data bank (NTDB) analysis.

PURPOSE: We sought to validate a risk model to predict venous thromboembolism (VTE) in pediatric trauma through an analysis of a contemporary cohort in the National Trauma Data Bank (NTDB). STUDY DESIGN: Prospective internal validation was performed in 10 randomly stratified samples of children (age 0-17 years) from the NTDB 2013-2016. Model discrimination was determined by calculation of the c-statistic (AUC), and calibration was evaluated through analysis of observed to expected (O:E) ratio. Recalibration was performed with application of a mixed-effects logistic regression. Model parameters were reestimated based on recalibration. RESULTS: Retrospective review identified 481,485 pediatric trauma patients with 729 (0.2%) episodes of VTE. Discriminatory ability of the model in all random cohorts was significant with AUC > 0.93 (p < 0.001). Inadequate calibration was noted in 4 of 10 cohorts and the entire dataset (p < 0.001) with an O:E ratio of 1.79. Model recalibration resulted in similar discrimination (AUC = 0.95) with improved calibration (O:E ratio = 1.33, p < 0.0001). CONCLUSION: Pediatric trauma prediction models can provide useful data for VTE risk stratification in injured children, but these models must be validated and calibrated prior to use. Recalibration of the model in question resulted in improved accuracy in a contemporary NTDB dataset. These data provide an appropriately calibrated and validated model for clinical use. LEVEL OF EVIDENCE: II - Prospective internal validation of a multivariable prediction model.

Minimizing variance in pediatric surgical care through implementation of a perioperative colon bundle: A multi-institution retrospective cohort study.

BACKGROUND: Employing an institutional initiative to minimize variance in pediatric surgical care, we implemented a set of perioperative bundled interventions for all colorectal procedures to reduce surgical site infections (SSIs). METHODS: Implementation of a standard colon bundle at two children's hospitals began in December 2014. Subjects who underwent a colorectal procedure during the study period were analyzed. Demographics, outcomes, and complications were compared with Wilcoxon Rank-Sum, Chi-square and Fisher exact tests, as appropriate. Multivariable logistic regression was performed to assess the influence of time period (independent of protocol implementation) on the rate of subsequent infection. RESULTS: One hundred and forty-five patients were identified (preprotocol=68, postprotocol= 77). Gender, diagnosis, procedure performed and wound classification were similar between groups. Superficial SSIs (21% vs. 8%, p=0.031) and readmission (16% vs. 4%, p=0.021) were significantly decreased following implementation of a colon bundle. Median hospital days, cost, reoperation, intraabdominal abscess, and anastomotic leak were unchanged before and after protocol implementation (all p > 0.05). Multivariable logistic regression found time period to be independent of SSIs (OR: 0.810, 95% CI: 0.576-1.140). CONCLUSION: Implementation of a standard pediatric perioperative colon bundle can reduce superficial SSIs. Larger prospective studies are needed to evaluate the impact of colon bundles in reducing complications, hospital stay and cost. LEVEL OF EVIDENCE: III - Retrospective cohort study.

Pediatric trauma venous thromboembolism prediction algorithm outperforms current anticoagulation prophylaxis guidelines: a pilot study.

PURPOSE: Venous thromboembolism (VTE) in injured children is rare, but sequelae can be morbid and life-threatening. Recent trauma society guidelines suggesting that all children over 15 years old should receive thromboprophylaxis may result in overtreatment. We sought to evaluate the efficacy of a previously published VTE prediction algorithm and compare it to current recommendations. METHODS: Two institutional trauma registries were queried for all pediatric (age < 18 years) patients admitted from 2007 to 2018. Clinical data were applied to the algorithm and the area under the receiver operating characteristic (AUROC) curve was calculated to test algorithm efficacy. RESULTS: A retrospective review identified 8271 patients with 30 episodes of VTE (0.36%). The VTE prediction algorithm classified 51 (0.6%) as high risk (> 5% risk), 322 (3.9%) as moderate risk (1-5% risk) and 7898 (95.5%) as low risk (< 1% risk). AUROC was 0.93 (95% CI 0.89-0.97). In our population, prophylaxis of the 'moderate-' and 'high-risk' cohorts would outperform the sensitivity (60% vs. 53%) and specificity (96% vs. 77%) of current guidelines while anticoagulating substantially fewer patients (373 vs. 1935, p < 0.001). CONCLUSION: A VTE prediction algorithm using clinical variables can identify injured children at risk for venous thromboembolic disease with more discrimination than current guidelines. Prospective studies are needed to investigate the validity of this model. LEVEL OF EVIDENCE: III-Clinical decision rule evaluated in a single population.

Perioperative neutropenia is not an independent risk factor for infectious complications of central venous line placement in children: A propensity score-matched analysis.

BACKGROUND: The infectious risk of central venous line (CVL) placement in children with neutropenia (absolute neutrophil count [ANC] <500/mm3) is not well defined. This study aims to investigate the early (≤30 days) and late (>30 days) infectious complications of CVLs placed in pediatric patients with and without neutropenia. METHODS: A retrospective review was conducted of all CVLs placed by pediatric surgeons at two institutions from 2010 to 2017. Multivariable logistic regression was performed to identify risk factors for line infection. Propensity score-matched cohorts of patients with and without neutropenia were compared in a 1:1 ratio. Wilcoxon rank-sum, Chi-square, Fisher's exact, and log-rank tests were also performed. RESULTS: Review identified 1,102 CVLs placed in 937 patients. Fifty-four patients were neutropenic at the time of placement. Multivariable analysis demonstrated tunneled catheters and subclavian access as associated with line infection. The propensity score-matched cohort included 94 patients, 47 from each group. Demographic and preoperative data were similar between the groups (p > 0.05). Patients with neutropenia were no more likely to develop early (4.3% vs. 2.1%, p = 1.000) or late (19.1% vs. 17.0%, p = 1.000) infectious complications than patients without neutropenia, with similar median time to infection (141 vs. 222 days, p = 0.370). CONCLUSION: A policy of selective CVL placement in neutropenic patients with standardized postoperative line maintenance is safe. Future directions include defining criteria by which neutropenic patients could be prospectively selected for safe CVL placement. LEVEL OF EVIDENCE: II - Retrospective cohort study.

A Natural History of Gastrojejunostomy Tubes in Children.

BACKGROUND: Gastrojejunostomy (GJ) tubes are frequently used to provide nutrition in patients who do not tolerate gastric feeding. Despite their widespread use, there is little literature on the lifespan of GJ tubes, reasons for failure, and recommendations for optimal techniques and timing of replacement. We aimed to evaluate the natural history of GJ tubes in pediatric patients. MATERIALS AND METHODS: We reviewed all pediatric patients who underwent GJ tube placement or exchange at our institution from January 2012 to July 2018. Demographic data, time, and indication for replacement or removal of GJ tubes were collected. End points were permanent removal of GJ tube or mortality. RESULTS: Seventy-nine patients underwent 205 GJ tube procedures with a median of 2 GJ tubes per patient. Median GJ tube lifespan was 98 d (interquartile range = 54-166). The two most common indications for tube exchange were structural or mechanical problems (43.1%) and GJ tube dislodgement (34.6%). Although most GJ tube exchanges (66%) were performed under general anesthesia or with moderate sedation, 34% of exchanges were done without sedation. During the study period, 12 patients (15.2%) died from their primary disease, nine patients (11.4%) required subsequent fundoplication, one (1.3%) underwent a jejunostomy, and 23 (29.1%) progressed to gastric feeds without fundoplication at a median time of 208 d. CONCLUSIONS: GJ tubes offer a safe and effective feeding option in patients intolerant of gastric feeding. GJ tubes fail most commonly from intrinsic structural or mechanical issues, and many patients ultimately tolerate gastric feeds without need for further intervention. Exchange of tubes without anesthesia is a viable option.

Routine Chest Radiographs in Children After Image-Guided Central Lines Offer Little Diagnostic Value.

BACKGROUND: The aim of this study was to investigate the utility of postoperative chest radiograph (CXR) after image-guided central venous line (CVL) placement in children. METHODS: A retrospective review was conducted of all tunneled CVLs placed at two pediatric institutions from 2010 to 2017. A subgroup analysis comparing a clinically driven approach to postoperative imaging against routine imaging was performed. RESULTS: During the study period, 1080 lines were placed in 915 patients. There were 892 postoperative CXRs (82.6%). An abnormality was seen on 40 radiographs (4.5%, n = 891), with 16 false-positive (1.3%) and 5 false-negative (0.6%) CXRs. The sensitivity and specificity of CXR to identify complications requiring intervention were 50.0% (95% confidence interval [95% CI], 10.0-90.0) and 95.8% (95% CI, 94.5-97.1), respectively. Positive predictive value of CXR was 7.5% (95% CI, 0-15.7) with a negative predictive value of 99.6% (95% CI, 99.2-100). A clinically driven approach to postoperative imaging was associated with 41% decrease in CXR (P < 0.001) without increased incidence of missed complications. Only three complications requiring intervention (0.3%) were suspected on postoperative CXR alone, and all of those were symptomatic before intervention. CONCLUSIONS: Routine postoperative CXR offers minimal value in identifying technical complications requiring intervention after image-guided CVL placement in asymptomatic children. We recommend abandoning this practice in favor of a clinical symptom-driven approach to postoperative imaging.

Rotational thromboelastometry predicts transfusion and disability in pediatric trauma.

BACKGROUND: Trauma-induced coagulopathy seen on rotational thromboelastometry (ROTEM) is associated with poor outcomes in adults; however, this relationship is poorly understood in the pediatric population. We sought to define thresholds for product-specific transfusion and evaluate the prognostic efficacy of ROTEM in injured children. METHODS: Demographics, ROTEM, and clinical outcomes from severely injured children (age, < 18 years) admitted to a Level I trauma center between 2014 and 2018 were retrospectively analyzed. Receiver operating characteristic curves were plotted and Youden indexes were calculated against the endpoint of packed red blood cell transfusion to identify thresholds for intervention. The ROTEM parameters were compared against the clinical outcomes of mortality or disability at discharge. RESULTS: Ninety subjects were reviewed. Increased tissue factor-triggered extrinsic pathway (EXTEM) clotting time (CT) >84.5 sec (p = 0.049), decreased EXTEM amplitude at 10 minutes (A10) <43.5 mm (p = 0.025), and decreased EXTEM maximal clot firmness (MCF) <64.5 mm (p = 0.026) were associated with need for blood product transfusion. Additionally, EXTEM CT longer than 68.5 seconds was associated with mortality or disability at discharge. CONCLUSION: Coagulation dysregulation on thromboelastometry is associated with disability and mortality in children. Based on our findings, we propose ROTEM thresholds: plasma transfusion for EXTEM CT longer than 84.5 seconds, fibrinogen replacement for EXTEM A10 less than 43.5 mm, and platelet transfusion for EXTEM MCF less than 64.5 mm. LEVEL OF EVIDENCE: Prognostic, Level III; Therapeutic, Level IV.

Anillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics.

RhoA stimulates cell contractility by recruiting downstream effectors to the cortical plasma membrane. We now show that direct binding by anillin is required for effective signaling: this antagonizes the otherwise labile membrane association of GTP-RhoA to promote effector recruitment. However, since its binding to RhoA blocks access by other effectors, we demonstrate that anillin must also concentrate membrane phosphoinositide-4,5-P2 (PIP2) to promote signaling. We propose and test a sequential pathway where GTP-RhoA first binds to anillin and then is retained at the membrane by PIP2 after it disengages from anillin. Importantly, re-binding of membrane GTP-RhoA to anillin, regulated by the cortical density of anillin, creates cycles through this pathway. These cycles repeatedly reset the dissociation kinetics of GTP-RhoA, substantially increasing its dwell time to recruit effectors. Thus, anillin regulates RhoA signaling by a paradigm of kinetic scaffolding that may apply to other signals whose efficacy depends on their cortical dwell times.

Nephron progenitor commitment is a stochastic process influenced by cell migration.

Progenitor self-renewal and differentiation is often regulated by spatially restricted cues within a tissue microenvironment. Here, we examine how progenitor cell migration impacts regionally induced commitment within the nephrogenic niche in mice. We identify a subset of cells that express Wnt4, an early marker of nephron commitment, but migrate back into the progenitor population where they accumulate over time. Single cell RNA-seq and computational modelling of returning cells reveals that nephron progenitors can traverse the transcriptional hierarchy between self-renewal and commitment in either direction. This plasticity may enable robust regulation of nephrogenesis as niches remodel and grow during organogenesis.

Branching morphogenesis in the developing kidney is not impacted by nephron formation or integration.

Branching morphogenesis of the ureteric bud is integral to kidney development; establishing the collecting ducts of the adult organ and driving organ expansion via peripheral interactions with nephron progenitor cells. A recent study suggested that termination of tip branching within the developing kidney involved stochastic exhaustion in response to nephron formation, with such a termination event representing a unifying developmental process evident in many organs. To examine this possibility, we have profiled the impact of nephron formation and maturation on elaboration of the ureteric bud during mouse kidney development. We find a distinct absence of random branch termination events within the kidney or evidence that nephrogenesis impacts the branching program or cell proliferation in either tip or progenitor cell niches. Instead, organogenesis proceeds in a manner indifferent to the development of these structures. Hence, stochastic cessation of branching is not a unifying developmental feature in all branching organs.