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Solid organ injury (SOI) is common in children who experience abdominal trauma, and the management of such injuries has evolved significantly over the past several decades. In 2000, the American Pediatric Surgical Association (APSA) published the first societal guidelines for the management of blunt spleen and/or liver injury (BLSI), advocating for optimized resource utilization while maintaining patient safety. Nonoperative management (NOM) has become the mainstay of treatment for SOI, and since the publication of the APSA guidelines, numerous groups have evaluated how invasive procedures, hospitalization, and activity restrictions may be safely minimized in children with SOI. Here, we review the current evidence-based management guidelines in place for the treatment of injuries to the spleen, liver, kidney, and pancreas in children, including initial evaluation, inpatient management, and long-term care, as well as gaps that exist in the current literature that may be targeted for further optimization of protocols for pediatric SOI.

Background. Mesenchymal chondrosarcoma is an aggressive, uncommon histologic entity arising in bone and soft tissues. We reviewed our institutional experience with this rare diagnosis. Methods. We conducted a retrospective chart review on patients with mesenchymal chondrosarcoma over a 24-year period. Clinicopathologic and radiographic features were reviewed. Results. Twelve patients were identified. Nine were females; median age was 14.5 years (1.2–19.7 years). The most common site was the head/neck (7/12). Disease was localized in 11/12 patients (one with lung nodules). Six with available tissue demonstrated NCOA2 rearrangement by FISH. Six underwent upfront surgical resection, and six received neoadjuvant therapy (2 chemotherapy alone and 4 chemotherapy and radiation). All patients received adjuvant chemotherapy (most commonly ifosfamide/doxorubicin) and/or radiation (median dose 59.4 Gy). At a median follow-up of 4.8 years, 5-year disease-free survival and overall survival were 68.2% (95% CI 39.8%, 96.6%) and 88.9% (95% CI 66.9%, 100%). Two patients had distant recurrences at 15 and 42 months, respectively. Conclusion. Aggressive surgical resection of mesenchymal chondrosarcoma with chemoradiotherapy yields excellent local control and may reduce likelihood of late recurrence. Characterization of downstream targets of the HEY1-NCOA2 fusion protein, xenograft models, and drug screening are needed to identify novel therapeutic strategies.

Machine-learning can elucidate complex relationships/provide insight to important variables for large datasets. This study aimed to develop an accurate model to predict neonatal surgical site infections (SSI) using different statistical methods. The 2012–2015 National Surgical Quality Improvement Program-Pediatric for neonates was utilized for development and validations models. The primary outcome was any SSI. Models included different algorithms: full multiple logistic regression (LR), a priori clinical LR, random forest classification (RFC), and a hybrid model (combination of clinical knowledge and significant variables from RF) to maximize predictive power. 16,842 patients (median age 18 days, IQR 3–58) were included. 542 SSIs (4%) were identified. Agreement was observed for multiple covariates among significant variables between models. Area under the curve for each model was similar (full model 0.65, clinical model 0.67, RF 0.68, hybrid LR 0.67); however, the hybrid model utilized the fewest variables (18). The hybrid model had similar predictability as other models with fewer and more clinically relevant variables. Machine-learning algorithms can identify important novel characteristics, which enhance clinical prediction models. •Operative time and open surgical technique were associated with greater odds of SSI.•Preoperative supplemental nutrition was associated with increased odds of SSI.•Hybrid prediction model combined clinical knowledge and random forest results.•Hybrid prediction model was more parsimonious with similar predictability.

Purpose Variation in management characterizes treatment of infants with a congenital pulmonary airway malformation (CPAM). This review addresses six clinically applicable questions using available evidence to provide recommendations for the treatment of these patients. Methods Questions regarding the management of a pediatric patient with a CPAM were generated. English language articles published between 1960 and 2014 were compiled after searching Medline and OvidSP. The articles were divided by subject area and by the question asked, then reviewed and included if they specifically addressed the proposed question. Results 1040 articles were identified on initial search. After screening abstracts per eligibility criteria, 130 articles were used to answer the proposed questions. Based on the available literature, resection of an asymptomatic CPAM is controversial, and when performed is usually completed within the first six months of life. Lobectomy remains the standard resection method for CPAM, and can be performed thoracoscopically or via thoracotomy. There is no consensus regarding a monitoring protocol for observing asymptomatic lesions, although at least one chest computerized tomogram (CT) should be performed postnatally for lesion characterization. An antenatally identified CPAM can be evaluated with MRI if fetal intervention is being considered, but is not required for the fetus with a lesion not at risk for hydrops. Prenatal consultation should be offered for infants with CPAM and encouraged for those infants in whom characteristics indicate risk of hydrops. Conclusions Very few articles provided definitive recommendations for care of the patient with a CPAM and none reported Level I or II evidence. Based on available information, CPAMs are usually resected early in life if at all. A prenatally diagnosed congenital lung lesion should be evaluated postnatally with CT, and prenatal counseling should be undertaken in patients at risk for hydrops.

Purpose There is still debate over the safest route for the placement of long-term central venous access devices. The aim of this study was to review a large, single-institution experience to determine the impact of access location on peri-operative complications. Methods The records of patients undergoing subcutaneous port (SQP) and tunneled catheter insertion over a seven-year period were reviewed. Vein cannulated (subclavian (SCV) versus internal jugular (IJ) vein), and 30-day complications were assessed. Surgical complications included pneumothorax, hemothorax, infections, arrhythmia or malpositioning requiring intervention. Results A total of 1,309 patients were included (618 SQP, 691 tunneled catheters). The location for insertion was SCV (909, 69.4%) and IJ (400, 30.6%). There were 69 complications (5.2%) (41, 4.5% SCV, 28, 7.0% IJV) including: malpositioning/malfunctioning (SCV 13, 1.4% and IJV 14, 3.0%), pneumothorax (SCV 4, 0.4% and IJV 1, 0.3%), hemothorax (SCV 0 and IJV 1, 0.3%), arrhythmia (SCV 1, 0.1%, and IJV 0), and infection within 30 days of placement (SCV 20, 2.2% and IJ 11, 2.8%). The complication rates were not significantly different based on site ( p  = 0.080). Conclusion There was no significant difference in complication rates when using the subclavian versus the internal jugular vein as the site for long-term central venous access. Level of evidence III, retrospective comparative study.

PurposeTo describe the practice pattern for routine laboratory and imaging assessment of children following blunt abdominal trauma (BAT).MethodsChildren (age < 16 years) presenting to 14 pediatric trauma centers following BAT over a 1-year period were prospectively identified. Injury, demographic, routine laboratory and imaging utilization data were collected. Descriptive, comparative, and correlation analysis was performed.Results2188 children with a median age of 8 (4,12) years were included and the median injury severity score was 5 (1,10). There were significant differences in activation status, injury severity, and mechanism across centers; however, there was no correlation of level of activation, injury severity, or severe mechanism with test utilization. Routine laboratory and imaging utilization for hematocrit, hepatic enzymes, pancreatic enzymes, base deficit urine microscopy, chest and pelvis X-ray, and abdominal computed tomography (CT) varied significantly among centers. Only obtaining a hematocrit had a moderate correlation with CT use. There was no correlation between centers that were high or low frequency laboratory utilizers with CT use.ConclusionsWide variability exists in the routine initial laboratory and imaging assessment in children following BAT. This represents an opportunity for quality improvement in pediatric trauma.Level of evidenceLevel II.

Background We have shown that continuous systemic delivery of interferon beta (IFN-β) remodels dysfunctional tumor vasculature, thereby improving tumor perfusion and enhancing delivery and efficacy of chemotherapeutic drugs. We hypothesized that because of their inherent tumor tropism, neural progenitor cells (NPCs) engineered to express IFN-β could also effect maturation of tumor vasculature without generating high systemic levels of IFN-β. Methods Mice with luciferase-expressing disseminated human neuroblastoma were divided into four groups of equal tumor burden by bioluminescence imaging: (1) untreated controls; (2) NPC-IFN-β only; (3) cyclophosphamide (CTX) only; and (4) NPC-IFN-β in combination with CTX. Two million NPC-IFN-β cells were administered twice, 7 days apart, starting 21 days after tail vein administration of tumor cells. CTX was administered every 6 days for three doses. Mice were killed at 6 weeks, livers and kidneys weighed, and tumor removed for immunohistochemical staining for endothelial cells (CD34), pericytes (α-SMA), apoptosis (TUNEL [terminal deoxynucleotidyl transferase dUTP nick-end labeling]), and diI-labeled NPCs. Results Fluorescent-labeled NPCs confirmed localization of these cells to tumors. The α-SMA/CD34 ratio, a marker for vascular maturation, greatly increased in NPC-IFN-β-treated tumors compared with controls. Bioluminescent signal from luciferase-expressing tumor cells, reflecting tumor burden, was lower with combination therapy than control or either monotherapy, and combination therapy resulted in far less tumor burden by weight in the kidneys and liver. Conclusions Targeted delivery of IFN-β with NPCs produced low circulating levels of IFN-β, yet the maturing effect on the tumor vasculature and the enhanced efficacy of adjuvant therapy was maintained. Thus, combination therapy of NPC-IFN-β with CTX warrants further investigation for the treatment of high-risk neuroblastoma patients.

Background Type 2 diabetes in young people is an aggressive disease with a greater risk of complications leading to increased morbidity and mortality during the most productive years of life. Prevalence in the UK and globally is rising yet experience in managing this condition is limited. There are no consensus guidelines in the UK for the assessment and management of paediatric type 2 diabetes. Methods Multidisciplinary professionals from The Association of Children’s Diabetes Clinicians (ACDC) and the National Type 2 Diabetes Working Group reviewed the evidence base and made recommendations using the Grading Of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Results and discussion Young people with type 2 diabetes should be managed within a paediatric diabetes team with close working with adult diabetes specialists, primary care and other paediatric specialties. Diagnosis of diabetes type can be challenging with many overlapping features. Diabetes antibodies may be needed to aid diagnosis. Co-morbidities and complications are frequently present at diagnosis and should be managed holistically. Lifestyle change and metformin are the mainstay of early treatment, with some needing additional basal insulin. GLP1 agonists should be used as second-line agents once early ketosis and symptoms are controlled. Glycaemic control improves microvascular but not cardiovascular risk. Reduction in excess adiposity, smoking prevention, increased physical activity and reduction of hypertension and dyslipidaemia are essential to reduce major adverse cardiovascular events. Conclusions This evidence-based guideline aims to provide a practical approach in managing this condition in the UK.

Invasive pathogens interface with the host and its resident microbiota through interkingdom signaling. The bacterial receptor QseC, which is a membrane-bound histidine sensor kinase, responds to the host stress hormones epinephrine and norepinephrine and the bacterial signal AI-3, integrating interkingdom signaling at the biochemical level. Importantly, the QseC signaling cascade is exploited by many bacterial pathogens to promote virulence. Here, we translated this basic science information into development of a potent small molecule inhibitor of QseC, LED209. Extensive structure activity relationship (SAR) studies revealed that LED209 is a potent prodrug that is highly selective for QseC. Its warhead allosterically modifies lysines in QseC, impairing its function and preventing the activation of the virulence program of several Gram-negative pathogens both in vitro and during murine infection. LED209 does not interfere with pathogen growth, possibly leading to a milder evolutionary pressure toward drug resistance. LED209 has desirable pharmacokinetics and does not present toxicity in vitro and in rodents. This is a unique antivirulence approach, with a proven broad-spectrum activity against multiple Gram-negative pathogens that cause mammalian infections. IMPORTANCE There is an imminent need for development of novel treatments for infectious diseases, given that one of the biggest challenges to medicine in the foreseeable future is the emergence of microbial antibiotic resistance. Here, we devised a broad-spectrum antivirulence approach targeting a conserved histidine kinase, QseC, in several Gram-negative pathogens that promotes their virulence expression. The LED209 QseC inhibitor has a unique mode of action by acting as a prodrug scaffold to deliver a warhead that allosterically modifies QseC, impeding virulence in several Gram-negative pathogens. There is an imminent need for development of novel treatments for infectious diseases, given that one of the biggest challenges to medicine in the foreseeable future is the emergence of microbial antibiotic resistance. Here, we devised a broad-spectrum antivirulence approach targeting a conserved histidine kinase, QseC, in several Gram-negative pathogens that promotes their virulence expression. The LED209 QseC inhibitor has a unique mode of action by acting as a prodrug scaffold to deliver a warhead that allosterically modifies QseC, impeding virulence in several Gram-negative pathogens.

Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine. In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248. Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebos −1·29%, 95% CI −14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, −6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (–12·9%, −34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%, −13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, −5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, −11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected. Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need. National Institute for Health Research Policy Research Programme