Risk Factors for Admission Hyperthermia and Associated Outcomes in Infants Born Preterm.

Maternal, placental, and neonatal factors were compared between infants born at ≤29 weeks of gestational age with admission hyperthermia (>37.5○C) and euthermia (36.5-37.5○C). Admission hyperthermia was associated with longer duration of face-mask positive-pressure ventilation and infant's temperature ≥37.5○C in the delivery room. Infants born preterm with admission hyperthermia had greater odds of developing necrotizing enterocolitis and neurodevelopmental impairment.

Value of perilesional biopsies in multiparametric magnetic resonance imaging-targeted biopsy and systematic biopsy in detection of prostate cancer: results of a prospective, non-randomized, surgeon-blinded study.

PURPOSE: The goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men. METHODS: This prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels < 20 ng/ml and ≥ one PI-RADS lesion (grades 3-5) per prostate lobe. Prostate biopsy was performed by two urologists. The first performed the MR-fusion biopsy with 3-5 targeted biopsies (TB) and 6 PB in a standardized pattern. The second performed the systematic (12-fold) biopsy (SB) without knowledge of the MR images. Primary outcome of this study is absence or presence of csPCa (≥ ISUP grade 2) comparing TB, PB and SB, using McNemar test. RESULTS: Analyses were performed for each PI-RADS lesion (n = 218). There was a statistically significant difference in csPC detection rate of TB + SB between PI-RADS 3, 4 and 5 lesions (18.0% vs. 42.5% vs. 82.6%, p < 0.001) and TB + PB (19.7% vs. 29.1% vs. 78.3%). Comparing only maximum ISUP grade per lesion, even SB plus TB plus PB did not detect more csPCa compared to SB plus TB (41.3% vs. 39.9%, p > 0.05). CONCLUSION: We present prospective study data investigating the role of perilesional biopsy in detection of prostate cancer. We detected no statistically significant difference in the detection of csPCa by the addition of PB. Therefore, we recommend continuing 12-fold bilateral SB in addition to TB.

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

PURPOSE: We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. MATERIALS AND METHODS: All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. RESULTS: In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. CONCLUSIONS: The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.

Robotic-assisted vs. open ureteral reimplantation: a multicentre comparison.

PURPOSE: Open ureteral reimplantation is considered the standard surgical approach to treat distal ureteral strictures or injuries. These procedures are increasingly performed in a minimally invasive and robotic-assisted manner. Notably, no series comparing perioperative outcomes and safety of the open vs. robotic approach are available so far. METHODS: In this retrospective multi-center study, we compared data from 51 robotic ureteral reimplantations (RUR) with 79 open ureteral reimplantations (OUR). Both cohorts were comparatively assessed using different baseline characteristics and perioperative outcomes. Moreover, a multivariate logistic regression for independent predictors was performed. RESULTS: Surgery time, length of hospital stay and dwell time of bladder catheter were shorter in the robotic cohort, whereas estimated blood loss, postoperative blood transfusion rate and postoperative complications were lower than in the open cohort. In the multivariate linear regression analysis, robotic approach was an independent predictor for a shorter operation time (coefficient - 0.254, 95% confidence interval [CI] - 0.342 to - 0.166; p < 0.001), a lower estimated blood loss (coefficient - 0.390, 95% CI - 0.549 to - 0.231, p < 0.001) and a shorter length of hospital stay (coefficient - 0.455, 95% CI - 0.552 to - 0.358, p < 0.001). Moreover, robotic surgery was an independent predictor for a shorter dwell time of bladder catheter (coefficient - 0.210, 95% CI - 0.278 to - 0.142, p < 0.001). CONCLUSION: RUR represents a safe alternative to OUR, with a shorter operative time, decreased blood loss and length of hospital stay. Prospective research are needed to further define the extent of the advantages of the robotic approach over open surgery.

Comparative Retrospective Assessment of the Effectiveness and Risk Factors of Fluoroquinolones, Cephalosporines, and Selective Antibiotic Prophylaxis for Transrectal Prostate Biopsy.

INTRODUCTION: Despite increasing resistance of enterobacteria against fluoroquinolones (FLU), they are still widely used during transrectal prostate biopsy (TRPB). This study was designed to analyse infectious complications and risk factors between FLU, cephalosporines (CEPH) and selective other antibiotics (O-AB) used during TRPB. METHODS: 664 patients were included retrospectively (152 FLU, 452 CEPH and 60 O-AB). Infectious complications were defined as fever >38.0°C, the in-house definition of complicated urinary tract infection (cUTI) (if all applied: fever >38.0°C, leucocytosis >11.000/µL and positive urine dipstick) or postinterventional bacteriuria. Hospitalisation rate, duration and comorbidities were also assessed. χ2 and Fisher's exact test were used for group comparison. Multivariate regression analysis assessed the association of comorbidities with infectious complications. RESULTS: FLU and CEPH were indifferent regarding infectious complications, however in the O-AB group significantly more common compared to FLU and CEPH (11.6, 13.3, 25%, p < 0.05). Duration of hospital stay in CEPH was significantly shorter compared to FLU and O-AB (4.1 vs. 6.3 vs. 8.2 days, p < 0.05). Arterial hypertension showed increased association with fever (OR 6.002 (1.178; 30.597) p = 0.031) and cUTI (OR 6.006 (1.207; 29.891) p = 0.029). CONCLUSION: Infectious complications were low and indifferent between FLU and CEPH but significantly more frequent in O-AB. Arterial hypertension was significantly associated with postinterventional fever and cUTI.

The tyrosine kinase inhibitor Dasatinib reduces cardiac steatosis and fibrosis in obese, type 2 diabetic mice.

BACKGROUND: Cardiac steatosis is an early yet overlooked feature of diabetic cardiomyopathy. There is no available therapy to treat this condition. Tyrosine kinase inhibitors (TKIs) are used as first or second-line therapy in different types of cancer. In cancer patients with diabetes mellitus, TKIs reportedly improved glycemic control, allowing insulin discontinuation. They also reduced liver steatosis in a murine model of non-alcoholic fatty liver disease. The present study aimed to determine the therapeutic effect of the second-generation TKI Dasatinib on lipid accumulation and cardiac function in obese, type 2 diabetic mice. We also assessed if the drug impacts extra-cardiac fat tissue depots. METHODS: Two studies on 21-week-old male obese leptin receptor mutant BKS.Cg-+Leprdb/+Leprdb/OlaHsd (db/db) mice compared the effect of Dasatinib (5 mg/kg) and vehicle (10% DMSO + 90% PEG-300) given via gavage once every three days for a week or once every week for four weeks. Functional and volumetric indices were studied using echocardiography. Post-mortem analyses included the assessment of fat deposits and fibrosis using histology, and senescence using immunohistochemistry and flow cytometry. The anti-adipogenic action of Dasatinib was investigated on human bone marrow (BM)-derived mesenchymal stem cells (MSCs). Unpaired parametric or non-parametric tests were used to compare two and multiple groups as appropriate. RESULTS: Dasatinib reduced steatosis and fibrosis in the heart of diabetic mice. The drug also reduced BM adiposity but did not affect other fat depots. These structural changes were associated with improved diastolic indexes, specifically the E/A ratio and non-flow time. Moreover, Dasatinib-treated mice had lower levels of p16 in the heart compared with vehicle-treated controls, suggesting an inhibitory impact of the drug on the senescence signalling pathway. In vitro, Dasatinib inhibited human BM-MSC viability and adipogenesis commitment. CONCLUSIONS: Our findings suggest that Dasatinib opposes heart and BM adiposity and cardiac fibrosis. In the heart, this was associated with favourable functional consequences, namely improvement in an index of diastolic function. Repurposing TKI for cardiac benefit could address the unmet need of diabetic cardiac steatosis.

Toward Improving Patient Equity in a Pediatric Emergency Department: A Framework for Implementation.

Disparities in health care delivery and health outcomes for patients in the emergency department (ED) by race, ethnicity, and language for care (REaL) are common and well documented. Addressing inequities from structural racism, implicit bias, and language barriers can be challenging, and there is a lack of data on effective interventions. We describe the implementation of a multifaceted equity improvement strategy in a pediatric ED using Kotter's model for change as a framework to identify the key drivers. The main elements included a data dashboard with quality metrics stratified by patient self-reported REaL to visualize disparities, a staff workshop on implicit bias and microaggressions, and several clinical and operational tools that highlight equity. Our next steps include refining and repeating interventions and tracking important patient outcomes, including timely pain treatment, triage assessment, diagnostic evaluations, and interpreter use, with the overall goal of improving patient equity by REaL over time. This article presents a roadmap for a disparity reduction intervention, which can be part of a multifaceted approach to address health equity in EDs.

Impact of Size for Gestational Age on Multivariate Analysis of Factors Associated with Necrotizing Enterocolitis in Preterm Infants: Retrospective Cohort Study.

OBJECTIVE: Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure. STUDY DESIGN: Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z-score < -2. RESULTS: Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z-score < 0. CONCLUSION: NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z-score < 0. KEY POINTS: · We studied 2,940 infants <33 weeks' GA.. · We assessed NEC.. · NEC was more frequent in SGA infants.. · NEC occurred 2 weeks later in SGA infants.. · NEC was associated with severe growth restriction..

The Current State of Pediatric Emergency Medicine Training in Emergency Medicine Residencies.

BACKGROUND: Several studies show that emergency medicine (EM) physicians are less comfortable caring for pediatric patients than adults. The state of pediatric training has not been comprehensively evaluated since 2000. OBJECTIVES: We sought to describe current pediatric education in EM residencies and to evaluate EM Program Director (PD) confidence in graduating trainees' abilities to care for pediatric patients. METHODS: We conducted an anonymous, cross-sectional survey study of EM PDs in August 2020. We collected program demographics, clinical rotations, and didactic methods. We used Likert scales to measure PD confidence in graduating residents' competence to care for pediatric and adult patients. RESULTS: We found e-mail addresses for 249 (93%) of 268 EM programs. One hundred nineteen (48%) PDs completed the survey. We include denominators to account for unanswered questions. Sixty-eight (59%) of 116 programs spend 10% to 20% of clinical time seeing pediatric patients. One hundred ten (91%) of 119 require a pediatric emergency medicine (PEM) rotation, 88/119 (83%) require pediatric intensive care, and 34/119 (29%) require neonatal intensive care. Seventy (62%) of 113 have curricula designed by PEM-trained faculty, 96/113 (85%) have PEM attendings teach lectures, and 77/113 (68%) spend 10% to 20% of didactic time on pediatric topics. Twenty-three (23%) of 106 PDs stated not all residents graduate with competence in pediatric resuscitation compared with 2/106 (2%) for adult resuscitation ( P < 0.05). CONCLUSIONS: Program directors report less confidence in graduating residents' competence in caring for pediatric patients compared with adult patients. We propose ideas to strengthen the quality of pediatric education in EM residencies.

Negative multiparametric magnetic resonance imaging for prostate cancer: further outcome and consequences.

PURPOSE: EAU guidelines recommend multiparametric MRI of the prostate (mpMRI) prior to biopsy to increase accuracy and reduce biopsies. Whether biopsy can be avoided in case of negative mpMRI remains unclear. Aim of this study is to evaluate predictors of overall prostate cancer (PCa) in negative mpMRI. METHODS: A total of 216 patients from 2018 to 2020 with suspicion of PCa and negative mpMRI (PI-RADS ≤ 2) were interviewed by telephone about outcome and further follow-up. Clinically significant PCa (csPCa) was defined as ISUP ≥ 2. Patients with vs. without biopsy and with vs. without PCa were compared. Univariate and multivariate analyses were performed to evaluate predictors of PCa occurrence in patients with negative mpMRI. RESULTS: 15.7% and 5.1% of patients with PI-RADS ≤ 2 on mpMRI showed PCa and csPCa, respectively. PCa patients had higher PSAD (0.14 vs. 0.09 ng/ml2; p = 0.001) and lower prostate volume (50.5 vs. 74.0 ml; p = 0.003). Patients without biopsy (25%) after MRI were older (69 vs. 65.5 years; p = 0.027), showed lower PSA (5.7 vs. 6.73 ng/ml; p = 0.033) and lower PSA density (0.09 vs. 0.1 ng/ml2; p = 0.027). Multivariate analysis revealed age (OR 1.09 [1.02-1.16]; p = 0.011), prostate volume (OR 0.982 [0.065; 0.997]; p = 0.027), total PSA level (OR 1.22 [1.01-1.47], p = 0.033), free PSA (OR 0.431 [0.177; 0.927]; p = 0.049) and no PI-RADS lesion vs PI-RADS 1-2 lesion (OR 0.38 [0.15-0.91], p = 0.032.) as predictive factors for the endpoint presence of PCa. CONCLUSIONS: Biopsy for selected patient groups (higher age, prostate volume and free PSA as well as lower PSA-Density) with negative mpMRI can be avoided, if sufficient follow-up care is guaranteed. Detailed counseling regarding residual risk for undetected prostate cancer should be mandatory.

Allyl-, Butyl- and Phenylethyl-Isothiocyanate Modulate Akt-mTOR and Cyclin-CDK Signaling in Gemcitabine- and Cisplatin-Resistant Bladder Cancer Cell Lines.

Combined cisplatin-gemcitabine treatment causes rapid resistance development in patients with advanced urothelial carcinoma. The present study investigated the potential of the natural isothiocyanates (ITCs) allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) to suppress growth and proliferation of gemcitabine- and cisplatin-resistant bladder cancer cells lines. Sensitive and gemcitabine- and cisplatin-resistant RT112, T24, and TCCSUP cells were treated with the ITCs, and tumor cell growth, proliferation, and clone formation were evaluated. Apoptosis induction and cell cycle progression were investigated as well. The molecular mode of action was investigated by evaluating cell cycle-regulating proteins (cyclin-dependent kinases (CDKs) and cyclins A and B) and the mechanistic target of the rapamycin (mTOR)-AKT signaling pathway. The ITCs significantly inhibited growth, proliferation and clone formation of all tumor cell lines (sensitive and resistant). Cells were arrested in the G2/M phase, independent of the type of resistance. Alterations of both the CDK-cyclin axis and the Akt-mTOR signaling pathway were observed in AITC-treated T24 cells with minor effects on apoptosis induction. In contrast, AITC de-activated Akt-mTOR signaling and induced apoptosis in RT112 cells, with only minor effects on CDK expression. It is concluded that AITC, BITC, and PEITC exert tumor-suppressive properties on cisplatin- and gemcitabine-resistant bladder cancer cells, whereby the molecular action may differ among the cell lines. The integration of these ITCs into the gemcitabine-/cisplatin-based treatment regimen might optimize bladder cancer therapy.

Improving Pediatric Readiness in General Emergency Departments: A Prospective Interventional Study.

OBJECTIVE: To describe the impact of a national interventional collaborative on pediatric readiness within general emergency departments (EDs). STUDY DESIGN: A prospective, multicenter, interventional study measured pediatric readiness in general EDs before and after participation in a pediatric readiness improvement intervention. Pediatric readiness was assessed using the weighted pediatric readiness score (WPRS) on a 100-point scale. The study protocol extended over 6 months and involved 3 phases: (1) a baseline on-site assessment of pediatric readiness and simulated quality of care; (2) pediatric readiness interventions; and (3) a follow-up on-site assessment of WPRS. The intervention phase included a benchmarking performance report, resources toolkits, and ongoing interactions between general EDs and academic medical centers. RESULTS: Thirty-six general EDs were enrolled, and 34 (94%) completed the study. Four EDs (11%) were located in Canada, and the rest were in the US. The mean improvement in WPRS was 16.3 (P < .001) from a baseline of 62.4 (SEM = 2.2) to 78.7 (SEM = 2.1), with significant improvement in the domains of administration/coordination of care; policies, protocol, and procedures; and quality improvement. Six EDs (17%) were fully adherent to the protocol timeline. CONCLUSIONS: Implementing a collaborative intervention model including simulation and quality improvement initiatives is associated with improvement in WPRS when disseminated to a diverse group of general EDs partnering with their regional pediatric academic medical centers. This work provides evidence that innovative collaboration facilitated by academic medical centers can serve as an effective strategy to improve pediatric readiness and processes of care.

Galectin-3 Identifies a Subset of Macrophages With a Potential Beneficial Role in Atherosclerosis.

OBJECTIVE: Galectin-3 (formerly known as Mac-2), encoded by the LGALS3 gene, is proposed to regulate macrophage adhesion, chemotaxis, and apoptosis. We investigated the role of galectin-3 in determining the inflammatory profile of macrophages and composition of atherosclerotic plaques. Approach and Results: We observed increased accumulation of galectin-3-negative macrophages within advanced human, rabbit, and mouse plaques compared with early lesions. Interestingly, statin treatment reduced galectin-3-negative macrophage accrual in advanced plaques within hypercholesterolemic (apolipoprotein E deficient) Apoe-/- mice. Accordingly, compared with Lgals3+/+:Apoe-/- mice, Lgals3-/-:Apoe-/- mice displayed altered plaque composition through increased macrophage:smooth muscle cell ratio, reduced collagen content, and increased necrotic core area, characteristics of advanced plaques in humans. Additionally, macrophages from Lgals3-/- mice exhibited increased invasive capacity in vitro and in vivo. Furthermore, loss of galectin-3 in vitro and in vivo was associated with increased expression of proinflammatory genes including MMP (matrix metalloproteinase)-12, CCL2 (chemokine [C-C motif] ligand 2), PTGS2 (prostaglandin-endoperoxide synthase 2), and IL (interleukin)-6, alongside reduced TGF (transforming growth factor)-ß1 expression and consequent SMAD signaling. Moreover, we found that MMP12 cleaves macrophage cell-surface galectin-3 resulting in the appearance of a 22-kDa fragment, whereas plasma levels of galectin-3 were reduced in Mmp12-/-:Apoe-/- mice, highlighting a novel mechanism where MMP12-dependent cleavage of galectin-3 promotes proinflammatory macrophage polarization. Moreover, galectin-3-positive macrophages were more abundant within plaques of Mmp12-/-:Apoe-/- mice compared with Mmp12+/+:Apoe-/- animals. CONCLUSIONS: This study reveals a prominent protective role for galectin-3 in regulating macrophage polarization and invasive capacity and, therefore, delaying plaque progression.

Scurvy in a Pediatric Patient With Autism and Limp: A Case Report.

BACKGROUND: Limping is a common chief complaint in the pediatric emergency department (ED) and can be difficult to assess in pediatric patients, particularly if they have developmental delay. CASE REPORT: We present a case of a 5-year-old male with nonverbal autism who presented with a progressive limp, weakness, pain, and rash over the course of 1 month. A magnetic resonance imaging scan of the pelvis performed while the patient was sedated revealed multifocal osseous marrow signal abnormalities, ultimately consistent with vitamin C deficiency or scurvy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Scurvy can present with nonspecific limp, rash, and bony pain and should be considered in pediatric patients with developmental/sensory delay who may restrict their diets. Emergency physicians should broaden their differential diagnoses to nutritional deficiencies such as scurvy in the evaluation of pediatric patients with limp.

Unintentional Pediatric Marijuana Exposures at a Tertiary Care Children's Hospital in Washington State: A Retrospective Review.

BACKGROUND: Recreational marijuana became commercially available in Washington State in 2014. Children with marijuana intoxication can have lethargy and altered mental status, often resulting in extensive workup. OBJECTIVES: The aim of this study was to quantify the incidence of pediatric marijuana exposure before and after marijuana legalization/commercial availability in Washington State at a tertiary care children's hospital. METHODS: Charts of patients 9 years or younger evaluated at a tertiary care pediatric hospital from October 8, 2007, to October 31, 2016, were retrospectively reviewed. Inclusion criteria were positive tetrahydrocannabinol urine toxicology screen and diagnosis consistent with unintentional marijuana exposure. Data included age, sex, exposure date range, symptoms, ancillary tests, consults, disposition, and marijuana source. Data were analyzed in R using descriptive statistics. RESULTS: Seventeen unintentional marijuana exposures were identified during our study period, 8 cases before and 9 cases after legalization of recreational marijuana, which is 1.19 events per year in the 6.75 years before legalization compared with 3.88 events per year in the 2.32 years after (P < 0.05). Age range was 17 months to 7 years, with a median age of 21 months. Eighty-two percent received laboratory tests, 47% underwent head computed tomography, 6% underwent lumbar puncture, and 100% underwent social work evaluation. Thirty-five percent were discharged from the emergency department, 47% were admitted to general medicine, and 18% were admitted to the critical care unit. CONCLUSIONS: Unintentional marijuana exposure incidence increased after legalization of recreational marijuana in Washington State at a tertiary care children's hospital. Providers should be aware of this increasing incidence. These data should be considered in the drafting of future marijuana legislation.

Development and Implementation of a Pediatric Telesimulation Intervention for Nurses in Community Emergency Departments.

The need for virtual education for nursing staff has dramatically increased because of social distancing measures after the coronavirus disease pandemic. Emergency departments in particular need to educate staff on caring for patients with coronavirus disease while concurrently continuing to ensure education related to core topic areas such as pediatric assessment and stabilization. Unfortunately, many nurse educators are currently unable to provide traditional in-person education and training to their nursing staff. Our inter-professional team aimed to address this through the rapid development and implementation of an emergency nursing telesimulation curriculum. This curriculum focused on the nursing assessment and initial stabilization of a child presenting to the emergency department in status epilepticus. This article describes the rapid development and implementation of a pediatric emergency nursing telesimulation. Our objectives in this article are (1) to describe the rapid creation of this curriculum using Kern's framework, (2) to describe the implementation of a fully online simulation-based pediatric emergency training intervention for nurse learners, and (3) to report learners' satisfaction with and feedback on this intervention.

Making surgery safer by centralization of care: impact of case load in penile cancer.

PURPOSE: Penile cancer is a rare but aggressive disease, often requiring a rapid and extensive surgical treatment of the primary tumor and staging or treatment of the inguinal lymph node basins. Current management and guidelines of the disease are mainly based on retrospective data, as there is a lack of controlled trials or large series. The purpose of this work is to review contemporary data on the impact of centralization and formation of rare disease networks on penile cancer care and outcomes. METHODS: This narrative, non-systematic review is based on publications retrieved by a PubMed and EMBASE search and on the current guidelines of the European Association of Urology, the National Institute for Health and Care Excellence, and the National Comprehensive Cancer network. RESULTS: The low case load, particularly in non-specialized centres, combined with limited evidence regularly results in a disparity between the treatment strategy and the guidelines. The suboptimal guideline adherence is specifically the case for organ-sparing surgery and surgical staging of the groin areas in selected cases. Treatment of the disease in high-volume referral centres has been shown to improve the use of organ-sparing surgery, the utilization of invasive lymph node staging in high-risk patients, and finally has resulted in increased survival rates. CONCLUSIONS: The management of penile cancer in disease networks and in countries where centralized healthcare is offered positively influences functional and oncological outcomes. We propose that governments and health care providers should be encouraged to centralize healthcare for rare tumors such as penile cancer.

Risk factors and molecular characterization of penile cancer: impact on prognosis and potential targets for systemic therapy.

PURPOSE OF REVIEW: To provide a comprehensive summary of risk factors, molecular machinery as well as potential therapeutic targets with a particular focus on literature published in the last 2 years on prognosis and treatment of penile cancer (PeCa). RECENT FINDINGS: E2F, LAMC2, MAML2, ID1 and IGFBP2 proteins were demonstrated to play a critical role for aggressive tumor behavior and might predict poor survival in PeCa. PD-L1 axis was confirmed as a promising pathway to serve as a therapeutic target. A number of genetic alterations were illuminated. In clinical testing, pan-HER tyrosine kinase inhibitor dacomitinib provided promising results in chemo-naïve and EGFR monoantibody nimotuzumab in chemotherapy-failed PeCa patients. SUMMARY: Knowledge of prognosis-relevant altered molecular pathways in PeCa is expanding paving the way for identification of potential therapeutic targets. Multicenter clinical trials in the setting of centralized PeCa care are warranted to foster effective marker-based individualized treatment strategies.

Role of TPBG (Trophoblast Glycoprotein) Antigen in Human Pericyte Migratory and Angiogenic Activity.

Objective- To determine the role of the oncofetal protein TPBG (trophoblast glycoprotein) in normal vascular function and reparative vascularization. Approach and Results- Immunohistochemistry of human veins was used to show TPBG expression in vascular smooth muscle cells and adventitial pericyte-like cells (APCs). ELISA, Western blot, immunocytochemistry, and proximity ligation assays evidenced a hypoxia-dependent upregulation of TPBG in APCs not found in vascular smooth muscle cells or endothelial cells. This involves the transcriptional modulator CITED2 (Atypical chemokine receptor 3 CBP/p300-interacting transactivator with glutamic acid (E)/aspartic acid (D)-rich tail) and downstream activation of CXCL12 (chemokine [C-X-C motif] ligand-12) signaling through the CXCR7 (C-X-C chemokine receptor type 7) receptor and ERK1/2 (extracellular signal-regulated kinases 1/2). TPBG silencing by siRNA transfection downregulated CXCL12, CXCR7, and pERK (phospho Thr202/Tyr204 ERK1/2) and reduced the APC migratory and proangiogenic capacities. TPBG forced expression induced opposite effects, which were associated with the formation of CXCR7/CXCR4 (C-X-C chemokine receptor type 4) heterodimers and could be contrasted by CXCL12 and CXCR7 neutralization. In vivo Matrigel plug assays using APCs with or without TPBG silencing evidenced TPBG is essential for angiogenesis. Finally, in immunosuppressed mice with limb ischemia, intramuscular injection of TPBG-overexpressing APCs surpassed naïve APCs in enhancing perfusion recovery and reducing the rate of toe necrosis. Conclusions- TPBG orchestrates the migratory and angiogenic activities of pericytes through the activation of the CXCL12/CXCR7/pERK axis. This novel mechanism could be a relevant target for therapeutic improvement of reparative angiogenesis.

Congenital Bronchial Stenosis Presenting as Neonatal Respiratory Distress: A Case Report.

BACKGROUND: Neonatal respiratory distress has a broad differential that includes cardiac, pulmonary, anatomic, and infectious etiologies. Congenital stenotic lesions of the trachea and bronchus are rare and can occur anywhere along the tracheobronchial tree. Patients with tracheobronchial stenosis typically present in the neonatal period with respiratory distress. CASE REPORT: We present a case of a 10-day-old term female who presented to the emergency department (ED) with tachypnea and increased work of breathing. She was found to have congenital bronchial stenosis of her right mainstem bronchus. She was stabilized in the ED and remained in the neonatal intensive care unit until successful slide tracheoplasty was performed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Congenital bronchial stenosis is a rare etiology of respiratory distress in a neonate. Anatomic lower airway abnormalities are an important cause of neonatal tachypnea and must remain on the differential. In addition to respiratory stabilization with noninvasive or invasive support, evaluation should be directed at determining the location and anatomic characteristics of the area of stenosis.