Incidence and survival of pediatric and adult hepatocellular carcinoma, United States, 2001-2020.

Importance: Hepatocellular carcinoma accounts for approximately 80% of liver neoplasms. Globally, hepatocellular carcinoma ranks as the third most lethal cancer, with the number of deaths expected to further increase by 2040. In adults, disparities in incidence and survival are well described while pediatric epidemiology is not well characterized. Objective: To describe incidence and survival for pediatric (ages 0-19 years) hepatocellular carcinoma cases and compare these measures to adults (ages ≥20 years) diagnosed with hepatocellular carcinoma. We evaluated demographic factors and clinical characteristics that influence incidence and outcomes. Design: Population-based cohort study. Setting: Incidence data from the US Cancer Statistics database from 2003 to 2020 and 5-year relative survival from the National Program of Cancer Registries from 2001 to 2019, covering 97% and 83% of the US population, respectively. Participants: 355,349 US Cancer Statistics and 257,406 the National Program of Cancer Registries patients were identified using ICD-O-3 C22.0 and 8170-5 codes. Main Outcomes and Measures: Incidence annual percent change (APC) and average APC (AAPC) using joinpoint regression. Five-year relative survival. All-cause survival estimated using multivariate Cox modeling. Corresponding 95% confidence intervals (CI) were calculated. Results: Incidence rate per 100,000 persons was 0.056 (95%CI:0.052-0.060) for pediatric cases and 7.793 (7.767-7.819) for adults. Incidence was stable in the pediatric population (0.3 AAPC, -1.1-1.7). In contrast, after periods of increase, incidence declined in adults after 2015 (-1.5 APC). Relative survival increased over time for both pediatric and adult ages and was higher for children and adolescents (46.4%, 95%CI:42.4-50.3) than adults (20.7%, 95%CI:20.5-20.9) overall and when stratified by stage. Regression modeling showed that non-Hispanic Black race and ethnicity was associated with higher risk of death in children and adolescents (1.48, 95%CI:1.07-2.05) and adults (1.11, 95%CI:1.09-1.12) compared to non-Hispanic white race and ethnicity. Conclusions and Relevance: Between 2003 and 2020 in the United States, pediatric incidence was stable while incidence in adults began to decline after 2015. Survival was higher across all stages for children and adolescents compared to adults. Non-Hispanic Black race and ethnicity showed a higher risk of death for both age groups. Further studies could explore the factors that influence these outcome disparities.

Impact of COVID-19-related restricted family presence policies on Canadian pediatric intensive care unit clinicians: a qualitative study.

PURPOSE: Pediatric intensive care units (PICUs) worldwide restricted family presence in response to the COVID-19 pandemic. We aimed to explore the experiences and impact of restricted family presence policies on Canadian PICU clinicians. METHODS: We conducted a qualitative study that followed an interpretive phenomenological design. Participants were PICU clinicians providing direct patient care in Canada during periods of COVID-19-related restricted family presence. We purposively sampled for maximum variation among survey participants who consented to be contacted for further research on the same topic. In-depth interviews were conducted remotely via telephone or video-call, audio-recorded, and transcribed. Interviews were inductively coded and underwent thematic analysis. Proposed themes were member-checked by interviewees. RESULTS: Sixteen PICU clinicians completed interviews. Interviewees practiced across Canada, represented a range of disciplines (eight nurses, two physicians, two respiratory therapists, two child life specialists, two social workers) and years in profession (0-34 years). We identified four themes representing the most meaningful aspects of restricted family presence for participants: 1) balancing infection control and family presence; 2) feeling disempowered by hospital and policy-making hierarchies; 3) empathizing with family trauma; and 4) navigating threats to the therapeutic relationship. CONCLUSION: Pediatric intensive care unit clinicians were impacted by restricted family presence policies during the COVID-19 pandemic. These policies contributed to feelings of disempowerment and challenged clinicians' perceived ability to provide the best family-centred care possible. Frontline expertise should be incorporated into the design and implementation of policies to best support family-centred care in any context and minimize risks of moral distress for PICU clinicians.

RéSUMé: OBJECTIF: Les unités de soins intensifs pédiatriques (USIP) du monde entier ont restreint la présence des familles en réponse à la la pandémie de COVID-19. Notre objectif était d'explorer les expériences et l'impact des politiques de restriction de la présence familiale sur les clinicien·nes des USIP canadiennes. MéTHODE: Nous avons mené une étude qualitative qui a suivi un plan phénoménologique interprétatif. Les participant·es étaient des clinicien·nes des USIP qui dispensaient des soins directs aux patient·es au Canada pendant les périodes de présence restreinte des familles en raison de la COVID-19. Nous avons délibérément échantillonné pour obtenir une variation maximale parmi les participant·es à l'enquête qui ont accepté d'être contacté·es pour d'autres recherches sur le même sujet. Des entretiens approfondis ont été menés à distance par téléphone ou par appel vidéo, enregistrés et transcrits. Les entretiens ont été codés de manière inductive et ont fait l'objet d'une analyse thématique. Les thèmes proposés ont été contrôlés par membre par les personnes interrogées. RéSULTATS: Seize cliniciennes et cliniciens des USIP ont passé des entrevues. Les personnes interrogées exerçaient partout au Canada, représentaient un éventail de disciplines (huit infirmiers et infirmières, deux médecins, deux inhalothérapeutes, deux spécialistes du milieu de l'enfant, deux travailleuses et travailleurs sociaux) et d'années d'expérience professionnelle (de 0 à 34 ans). Nous avons identifié quatre thèmes représentant les aspects les plus significatifs de la présence restreinte de la famille pour les participant·es : 1) l'équilibre entre la prévention des infections et la présence de la famille; 2) le sentiment d'être dépossédé·e par les hiérarchies de l'hôpital et de ne pas pouvoir participer à l'élaboration des politiques; 3) le sentiment d'empathie à l'égard des traumatismes familiaux; et 4) la réponse aux menaces qui ont pesé sur la relation thérapeutique. CONCLUSION: Les cliniciens et cliniciennes des unités de soins intensifs pédiatriques ont été touché·es par les politiques de restriction de la présence familiale pendant la pandémie de COVID-19. Ces politiques ont contribué à un sentiment d'impuissance et ont remis en question la capacité perçue des équipes à fournir les meilleurs soins possibles axés sur la famille. L'expertise de première ligne devrait être intégrée à la conception et à la mise en œuvre des politiques afin de mieux soutenir les soins axés sur la famille dans n'importe quel contexte et de minimiser les risques de détresse morale pour les cliniciennes et cliniciens des USIP.

Geriatric Genital Dermatology.

As women age, hormonal changes set the stage for a variety of vulvovaginal pathologies. Health care providers in long-term care facilities should be able to recognize and treat these conditions, especially because residents may be unable to communicate their discomfort. The objective of this article is to highlight the major vulvovaginal conditions affecting older women and provide up-to-date information on treatment for providers in long-term care facilities.

A comprehensive analysis of neuroblastoma incidence, survival, and racial and ethnic disparities from 2001 to 2019.

BACKGROUND: We characterize the incidence and 5-year survival of children and adolescents with neuroblastoma stratified by demographic and clinical factors based on the comprehensive data from United States Cancer Statistics (USCS) and the National Program of Cancer Registries (NPCR). METHODS: We analyzed the incidence of neuroblastoma from USCS (2003-2019) and survival data from NPCR (2001-2018) for patients less than 20 years old. Incidence trends were calculated by average annual percent change (AAPC) using joinpoint regression. Differences in relative survival were estimated comparing non-overlapping confidence intervals (CI). RESULTS: We identified 11,543 primary neuroblastoma cases in USCS. Age-adjusted incidence was 8.3 per million persons [95% CI: 8.2, 8.5], with an AAPC of 0.4% [95% CI: -0.1, 0.9]. Five-year relative survival from the NPCR dataset (n = 10,676) was 79.7% [95% CI: 78.9, 80.5]. Patients aged less than 1 year had the highest 5-year relative survival (92.5%). Five-year relative survival was higher for non-Hispanic White patients (80.7%) or Hispanic patients (80.8%) compared to non-Hispanic Black patients (72.6%). CONCLUSION: Neuroblastoma incidence was stable during 2003-2019. Differences in relative survival exist by sex, age, race/ethnicity, and stage; patients who were male, older, non-Hispanic Black, or with distant disease had worse survival. Future studies could seek to assess the upstream factors driving disparities in survival, and evaluate interventions to address inequities and improve survival across all groups.

Neuroblastoma in the Era of Precision Medicine: A Clinical Review.

The latest advances in treatment for patients with neuroblastoma are constantly being incorporated into clinical trials and clinical practice standards, resulting in incremental improvements in the survival of patients over time. Survivors of high-risk neuroblastoma (HRNBL), however, continue to develop treatment-related late effects. Additionally, for the majority of the nearly 50% of patients with HRNBL who experience relapse, no curative therapy currently exists. As technologies in diagnostic and molecular profiling techniques rapidly advance, so does the discovery of potential treatment targets. Here, we discuss the current clinical landscape of therapies for neuroblastoma in the era of precision medicine.

Extubation to High-Flow Nasal Cannula in Infants Following Cardiac Surgery: A Retrospective Cohort Study.

High-flow nasal cannula (HFNC) therapy is commonly used in the pediatric intensive care unit (PICU) for postextubation respiratory support. This hypothesis-generating retrospective cohort study aimed to compare postextubation PICU length of stay in infants extubated to HFNC and low flow oxygen (LF) in PICU following cardiac surgery. Of 136 infants (newborn to 1 year) who were intubated and mechanically ventilated in PICU following cardiac surgery, 72 (53%) were extubated to HFNC and 64 (47%) to LF. Compared with patients extubated to LF, those extubated to HFNC had significantly longer durations of cardiopulmonary bypass (152 vs. 109 minutes; p = 0.002), aortic cross-clamp (90 vs. 63 minutes; p = 0.003), and invasive mechanical ventilation (3.2 vs. 1.6 days; p < 0.001), although demographic and preoperative clinical variables were similar. No significant difference was observed in postextubation PICU length of stay between HFNC and LF groups in unadjusted analysis (3.3 vs. 2.6 days, respectively; p = 0.19) and after controlling for potential confounding variables (F [1,125] = 0.17, p = 0.68, R 2 = 0.16). Escalation of therapy was similar between HFNC and LF groups (8.3 vs. 14.1%; p = 0.41). HFNC was effective as rescue therapy for six patients in the LF group requiring escalation of therapy. Need for reintubation was similar between HFNC and LF groups (8.3 vs. 4.7%; p = 0.5). Although extubation to HFNC was associated with a trend toward longer postextubation PICU length of stay and was successfully used as rescue therapy for several infants extubated to LF, our results must be interpreted with caution given the limitations of our study.

Treatment of High-Risk Neuroblastoma.

High-risk neuroblastoma is a highly aggressive solid tumor that most commonly presents in early childhood. Advances in treatment through decades of clinical trials and research have led to improved outcomes. This review provides an overview of the current state of treatment for high-risk neuroblastoma.

A survey of pediatric intensive care unit clinician experience with restricted family presence during COVID-19.

PURPOSE: Limiting family presence runs counter to the family-centred values of Canadian pediatric intensive care units (PICUs). This study explores how implementing and enforcing COVID-19-related restricted family presence (RFP) policies impacted PICU clinicians nationally. METHODS: We conducted a cross-sectional, online, self-administered survey of Canadian PICU clinicians to assess experience and opinions of restrictions, moral distress (Moral Distress Thermometer, range 0-10), and mental health impacts (Impact of Event Scale [IES], range 0-75 and attributable stress [five-point Likert scale]). For analysis, we used descriptive statistics, multivariate regression modelling, and a general inductive approach for free text. RESULTS: Representing 17/19 Canadian PICUs, 368 of 388 respondents (94%) experienced RFP policies and were predominantly female (333/368, 91%), English speaking (338/368, 92%), and nurses (240/368, 65%). The mean (standard deviation [SD]) reported moral distress score was 4.5 (2.4) and was associated with perceived differential impact on families. The mean (SD) total IES score was 29.7 (10.5), suggesting moderate traumatic stress with 56% (176/317) reporting increased/significantly increased stress from restrictions related to separating families, denying access, and concern for family impacts. Incongruence between RFP policies/practices and PICU values was perceived by 66% of respondents (217/330). Most respondents (235/330, 71%) felt their opinions were not valued when implementing policies. Though respondents perceived that restrictions were implemented for the benefit of clinicians (252/332, 76%) and to protect families (236/315, 75%), 57% (188/332) disagreed that their RFP experience was mainly positive. CONCLUSION: Pediatric intensive care unit-based RFP rules, largely designed and implemented without bedside clinician input, caused increased psychological burden for clinicians, characterized as moderate moral distress and trauma triggered by perceived impacts on families.

RéSUMé: OBJECTIF: Limiter la présence de la famille va à l'encontre des valeurs centrées sur la famille des unités de soins intensifs pédiatriques (USIP) canadiennes. Cette étude explore comment la mise en œuvre et l'application des politiques de restriction de la présence familiale liées à la COVID-19 ont eu une incidence sur les cliniciennes et cliniciens des USIP à l'échelle nationale. MéTHODE: Nous avons mené un sondage transversal, en ligne et auto-administré auprès des cliniciens et cliniciennes des USIP canadiennes afin d'évaluer leur expérience et opinions sur les restrictions, la détresse morale (thermomètre de détresse morale, intervalle de 0 à 10) et les impacts sur la santé mentale (échelle d'impact des événements [EIE], intervalle de 0 à 75, et le stress qui peut y être attribué [échelle de Likert à cinq points]). Pour l'analyse, nous avons utilisé des statistiques descriptives, une modélisation de régression multivariée et une analyse inductive générale pour le texte libre. RéSULTATS: Représentant 17/19 USIP canadiennes, 368 des 388 personnes répondantes (94 %) ont vécu des politiques de restriction de la présence familiale et étaient principalement des femmes (333/368, 91 %), anglophones (338/368, 92 %) et infirmières (240/368, 65 %). Le score moyen (écart type [ET]) rapporté de détresse morale était de 4,5 (2,4) et était associé à l'impact différentiel perçu sur les familles. Le score moyen (ET) total de l'EIE était de 29,7 (10,5), ce qui suggère un stress traumatique modéré, 56 % (176/317) des personnes répondantes déclarant une augmentation ou une augmentation significative du stress associé aux restrictions liées à la séparation des familles, au refus d'accès et à la préoccupation pour les impacts familiaux. L'incongruité entre les politiques et les pratiques de restriction des visites familiales et les valeurs des USIP était perçue par 66 % des personnes répondantes (217/330). La plupart (235/330, 71 %) estimaient que leurs opinions n'étaient pas prises en compte lors de la mise en œuvre de politiques. Bien que les répondant·es aient perçu que les restrictions avaient été mises en œuvre dans l'intérêt des cliniciens et cliniciennes (252/332, 76 %) et pour protéger les familles (236/315, 75 %), 57 % (188/332) n'étaient pas d'accord pour dire que leur expérience de la restriction des visites familiales était principalement positive. CONCLUSION: Les règles de restriction de la présence familiale dans les unités de soins intensifs pédiatriques, en grande partie conçues et mises en œuvre sans l'avis du personnel clinique au chevet des patient·es, ont entraîné une augmentation du fardeau psychologique pour le personnel clinique, caractérisée par une détresse morale modérée et un traumatisme déclenché par des répercussions perçues sur les familles.

Launching a Teaching Academy (Virtually) During a Pandemic: Silver Linings to a Challenge.

The pandemic disrupted our plans to launch a Teaching Academy to formally support medical educators. Moving forward virtually provided a collaborative and supportive network to plan and deliver professional development activities to navigate pandemic challenges. Through sharing and practicing new teaching technologies together, the social connection and engagement with colleagues helped navigate pandemic challenges.

An unusual case of checkpoint-inhibitor-induced pleuropericarditis.

INTRODUCTION: Pembrolizumab is an immune checkpoint inhibitor that promotes effector T-cell functions on malignant cells by binding to programmed cell death protein 1 (PD-1). Pembrolizumab is well tolerated in most cases with an adverse event profile consisting mainly of pruritus, fatigue, and anorexia. Cardiotoxicity comprises 1% of the total adverse events. CASE REPORT: We present a case of a 64-year-old female with non-small cell lung cancer (NSCLC) who developed pleuropericarditis following pembrolizumab therapy. MANAGEMENT & OUTCOME: The patient was successfully managed with colchicine, furosemide, and timely initiation of methylprednisolone with the improvement of her symptoms. The decision to discontinue pembrolizumab was made, and six months after this intervention, the patient has remained asymptomatic. DISCUSSION: Clinicians should recognize these potential immune-mediated adverse effects to provide effective and timely management and optimize patient care.

Renal function in abdominal neuroblastoma patients undergoing proton radiotherapy.

BACKGROUND: The purpose of this study is to analyze renal function outcomes in abdominal neuroblastoma patients undergoing proton therapy (PT). PROCEDURE: From 2011 to 2019, two single-institution Institutional Review Board-approved protocols prospectively enrolled neuroblastoma patients for data collection. To assess renal function, serum creatinine (Cr), blood urea nitrogen (BUN), and creatinine clearance (CrCl) before proton therapy (pre-PT) were compared with the values at last follow-up. RESULTS: A total of 30 children with abdominal neuroblastoma with median age 3.5 years (range, 0.9-9.1) at time of PT were included in this study. All patients underwent chemotherapy and resection of primary tumor prior to PT. Two patients required radical nephrectomy. Median follow-up after PT was 35 months. Mean dose to ipsilateral and contralateral kidney was 13.9 and 5.4 Gy, respectively. No patients developed hypertension or renal dysfunction during follow-up. There was no statistically significant change in serum BUN (p = .508), CrCl (p = .280), or eGFR (p = .246) between pre-PT and last follow-up. CONCLUSION: At a median follow-up of almost 3 years, renal toxicity was uncommon after PT. Longer follow-up and larger patient cohort data are needed to further assess impact of PT on renal function in this population.

Progression-Free Survival and Patterns of Response in Patients With Relapsed High-Risk Neuroblastoma Treated With Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor.

PURPOSE: Although chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy. PATIENTS AND METHODS: Patients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded. Responses were evaluated using the International Neuroblastoma Response Criteria. RESULTS: One hundred forty-six patients were included. Tumors were MYCN-amplified in 50 of 134 (37%). Seventy-one patients (49%) had an objective response to I/T/DIN/GM-CSF (objective response; 29% complete response, 14% partial response [PR], 5% minor response [MR], 21% stable disease [SD], and 30% progressive disease). Of patients with SD or better at first post-I/T/DIN/GM-CSF disease evaluation, 22% had an improved response per International Neuroblastoma Response Criteria on subsequent evaluation (13% of patients with initial SD, 33% with MR, and 41% with PR). Patients received a median of 4.5 (range, 1-31) cycles. The median progression-free survival (PFS) was 13.1 months, and the 1-year PFS and 2-year PFS were 50% and 28%, respectively. The median duration of response was 15.9 months; the median PFS off all anticancer therapy was 10.4 months after discontinuation of I/T/DIN/GM-CSF. CONCLUSION: Approximately half of patients receiving I/T/DIN/GM-CSF for relapsed HRNB had objective responses. Patients with initial SD were unlikely to have an objective response, but > 1 of 3 patients with MR/PR on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended PFS in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed HRNB.

"I want to be there. I have to be there.": Parents' perceived barriers and facilitators to bedside presence in the pediatric intensive care unit.

Introduction: Parental presence at the bedside during a stressful pediatric intensive care unit (PICU) admission may improve child comfort, reduce parental anxiety, and enable family engagement. We performed this study to identify factors that parents perceive impact their capability, opportunity, and motivation to be at the bedside in PICU. Methods: We conducted a qualitative descriptive study using semi-structured interviews based on the Theoretical Domains Framework (TDF). We included parents of children admitted to the PICU for at least 24 h at IWK Health in Nova Scotia, Canada. Interviews were coded independently by two researchers using a directed content approach based on the TDF. We generated themes and subthemes, with the subthemes identified as factors impacting parental presence, and assigned TDF domains to each of the subthemes. Results: Fourteen primary caregivers (8 mother figures, 6 father figures) participated in 11 interviews. The factors associated with parental presence were captured by 6 themes: Understanding the Medicalized Child; Maintaining the Parent Role; Life Beyond the Hospital; Parental Intrinsic Responses and Coping; Support Structures; and The PICU Environment. Fifty-two barriers and enablers were identified within 13 TDF domains; 10 TDF domains were determined to be relevant to parental presence, which may be used to guide design of future interventions. Participants emphasized the importance of self-care to enable them to remain physically at their child's bedside and to be engaged in their care. Conclusions: Parents perceive multiple factors within 6 themes act as barriers or enablers to presence with their critically ill child in the PICU. Guided by relevant TDF domains, interventions may be designed to optimize presence, particularly engaged presence, which may improve health-related outcomes of children and their parents.

"We Aren't Meant to Go Through the Hardest Parts of Our Lives Alone": Family Experience With Restricted PICU Presence During the COVID-19 Pandemic.

CONTEXT: PICUs across Canada restricted family presence (RFP) in response to the COVID-19 pandemic from allowing two or more family members to often only one family member at the bedside. The objective of this study was to describe the experiences and impact of RFP on families of critically ill children to inform future policy and practice. HYPOTHESIS: RFP policies negatively impacted families of PICU patients and caused moral distress. METHODS AND MODELS: National, cross-sectional, online, self-administered survey. Family members of children admitted to a Canadian PICU between March 2020 and February 2021 were invited to complete the survey. RFP-attributable distress was measured with a modified distress thermometer (0-10). Closed-ended questions were reported with descriptive statistics and multivariable linear regression assessed factors associated with RFP-attributable distress. Open-ended questions were analyzed using inductive content analysis. RESULTS: Of 250 respondents who experienced RFP, 124 (49.6%) were restricted to one family member at the bedside. The median amount of distress that families attributed to RFP policies was 6 (range: 0-10). Families described isolation, removal of supports, and perception of trauma related to RFP. Most families (183, 73.2%) felt that policies were enforced in a way that made them feel valued by PICU clinicians, which was associated with less RFP-attributable distress. Differential impact was seen where families with lower household income indicated higher RFP-attributable distress score (2.35; 95% CI, 0.53-4.17; p = 0.03). Most respondents suggested that future policies should allow at least two family members at the bedside. INTERPRETATIONS AND CONCLUSIONS: Families of children admitted to PICUs during the COVID-19 pandemic described increased distress, trauma, and removal of supports due to RFP policies. Vulnerable families showed an increased odds of higher distress. Healthcare professionals played an important role in mitigating distress. Allowance of at least two family members at the bedside should be considered for future policy.

The Florida Clinical Skills Collaborative: A New Regional Consortium for the Assessment of Clinical Skills.

Discontinuation of the United States Medical Licensing Examination (USMLE) Step 2 Clinical Skills (CS) exam and Comprehensive Osteopathic Medical Licensing Examination (COMLEX) Level 2 Performance Evaluation (2-PE) raised questions about the ability of medical schools to ensure the clinical skills competence of graduating students. In February 2021, representatives from all Florida, United States, allopathic and osteopathic schools initiated a collaboration to address this critically important issue in the evolving landscape of medical education. A 5-point Likert scale survey of all members (n=18/20 individuals representing 10/10 institutions) reveals that initial interest in joining the collaboration was high among both individuals (mean 4.78, SD 0.43) and institutions (mean 4.69, SD 0.48). Most individuals (mean 4.78, SD 0.55) and institutions (mean 4.53, SD 0.72) are highly satisfied with their decision to join. Members most commonly cited a "desire to establish a shared assessment in place of Step 2 CS/2-PE" as their most important reason for joining. Experienced benefits of membership were ranked as the following: 1) Networking, 2) Shared resources for curriculum implementation, 3) Scholarship, and 4) Work towards a shared assessment in place of Step 2 CS/2-PE. Challenges of membership were ranked as the following: 1) Logistics such as scheduling and technology, 2) Agreement on common goals, 3) Total time commitment, and 4) Large group size. Members cited the "administration of a joint assessment pilot" as the highest priority for the coming year. Florida has successfully launched a regional consortium for the assessment of clinical skills competency with high levels of member satisfaction which may serve as a model for future regional consortia.

ERK Inhibitor Ulixertinib Inhibits High-Risk Neuroblastoma Growth In Vitro and In Vivo.

Neuroblastoma (NB) is a pediatric tumor of the peripheral nervous system. Approximately 80% of relapsed NB show RAS-MAPK pathway mutations that activate ERK, resulting in the promotion of cell proliferation and drug resistance. Ulixertinib, a first-in-class ERK-specific inhibitor, has shown promising antitumor activity in phase 1 clinical trials for advanced solid tumors. Here, we show that ulixertinib significantly and dose-dependently inhibits cell proliferation and colony formation in different NB cell lines, including PDX cells. Transcriptomic analysis revealed that ulixertinib extensively inhibits different oncogenic and neuronal developmental pathways, including EGFR, VEGF, WNT, MAPK, NGF, and NTRK1. The proteomic analysis further revealed that ulixertinib inhibits the cell cycle and promotes apoptosis in NB cells. Additionally, ulixertinib treatment significantly sensitized NB cells to the conventional chemotherapeutic agent doxorubicin. Furthermore, ulixertinib potently inhibited NB tumor growth and prolonged the overall survival of the treated mice in two different NB mice models. Our preclinical study demonstrates that ulixertinib, either as a single agent or in combination with current therapies, is a novel and practical therapeutic approach for NB.

Case report: Spindle cell neoplasm presenting as a spontaneous intestinal perforation in a term infant.

Spontaneous intestinal perforations in the neonatal population are mostly associated with low birth weight, prematurity, and necrotizing enterocolitis. Spontaneous intestinal perforation in the absence of these risk factors is extremely rare and should raise clinical concern for an underlying bowel pathology. Here we present a unique case of a normal-weight, full-term girl with spontaneous intestinal perforation due to a spindle cell neoplasm with a novel BRAF mutation and infantile fibrosarcoma-like morphology. Though rare, malignancy should be considered in the differential diagnosis for bowel perforation in an otherwise healthy, term infant as complete surgical excision can be curative.