Moving Beyond Hemangioma: Interactive, Multidisciplinary, Case-Based Teaching in Vascular Anomalies for Pediatric Residents.

Introduction: Vascular anomalies are a spectrum of disorders, including vascular tumors and malformations, that often require multispecialty care. The rarity and variety of these lesions make diagnosis, treatment, and management challenging. Despite the recognition of the medical complexity and morbidity associated with vascular anomalies, there is a general lack of education on the subject for pediatric primary care and subspecialty providers. A needs assessment and the lack of an available standardized teaching tool presented an opportunity to create an educational workshop for pediatric trainees using the POGIL (process-oriented guided inquiry learning) framework. Methods: We developed a 2-hour workshop consisting of an introductory didactic followed by small- and large-group collaboration and case-based discussion. The resource included customizable content for learning assessment and evaluation. Residents completed pre- and posttest assessments of content and provided written evaluations of the teaching session. Results: Thirty-four learners in pediatrics participated in the workshop. Session evaluations were positive, with Likert responses of 4.6-4.8 out of 5 on all items. Pre- and posttest comparisons of four content questions showed no overall statistically significant changes in correct response rates. Learners indicated plans to use the clinical content in their practice and particularly appreciated the interactive teaching forum and the comprehensive overview of vascular anomalies. Discussion: Vascular anomalies are complex, potentially morbid, and often lifelong conditions; multispecialty collaboration is key to providing comprehensive care for affected patients. This customizable resource offers a framework for trainees in pediatrics to appropriately recognize, evaluate, and refer patients with vascular anomalies.

Outcomes of a Peer Mentoring Circle: An Innovation to Improve Academic Physician Career Advancement in a Community Hospital Setting.

PROBLEM: Faculty retention is a prominent topic in academic medicine. Investment in faculty career development supports faculty vitality, advancement, and retention. Academic physicians in community-based settings far from their academic affiliate may find identifying local career advancement mentorship challenging. APPROACH: In June 2018, a career advancement in-service day at The Children's Hospital of San Antonio and Baylor College of Medicine in Houston was convened to design a peer mentoring circle (PMC). Using self-determination theory, this program aimed to help PMC members develop goals; schedule and attend regular meetings; format, review, and critique member curricula vitae and portfolios; and hold one another accountable to submitting award and promotion applications. OUTCOMES: Eleven inaugural PMC cohort members attended regular monthly meetings from July 2018 to June 2019 (median, 6 members per meeting). All members were competent in accessing the PMC repository of materials. Statistically significant improvement ( P < .01) was seen in self-reported knowledge and skills relevant to award or academic promotion support and resources. Compared with no patient care or teaching awards and 1 academic promotion among non-PMC faculty, 5 PMC members (45.5%) earned a patient care award, 4 (36.4%) earned a teaching award, and 5 of 10 faculty members (50.0%) achieved academic promotion ( P < .001 for all). On the retrospective pre-post survey, members endorsed several PMC strengths, including personal and emotional support, professional support, and accountability. NEXT STEPS: Next steps include establishing a local faculty development office, convening a second cohort, revising evaluation methods, expanding membership, and offering 1-on-1 career counseling. Community-based academicians who aim to replicate this program should organize a career advancement and faculty development in-service day, identify local faculty members to manage meetings, retain a repository of resources, set deadlines and hold one another accountable to them, and celebrate achievements and support one another in failure.

Teaching Sexual Orientation and Gender Identity in Pediatric Clinical Settings: A Training Workshop for Faculty and Residents.

Introduction: Health disparities for the lesbian, gay, bisexual, transgender, queer, intersex, asexual, all other genders, sexes, and sexualities (LGBTQIA+) population are striking. Yet, deliberate efforts to integrate sexual orientation and gender identity in pediatric education settings remain lacking. The type of formal training that pediatric educators currently have for teaching of sexual orientation and gender identity is unclear and limited, which led to the development and implementation of this curriculum. Methods: A 2-hour workshop was developed to address gaps in knowledge, equip faculty and resident educators with skills to apply key concepts in teaching activities, and motivate them to examine challenges and opportunities in teaching sexual orientation and gender identity principles in their routine duties in pediatric settings across the undergraduate and graduate education spectrum. Learning strategies of the workshop included learner activation, a didactic, and clinical cases with role-play opportunities. Participants completed evaluations at the end of the workshop. Results: The workshop was implemented in three varied educational settings in 2019. All 65 participants enrolled in the workshop completed the evaluations. Evaluations ranged from 4.6 to 4.9 on a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree). Participants reported workshop strengths and anticipated impact on their own teaching and clinical practice. Discussion: Stark health disparities for the LGBTQIA+ population and gaps in relevant curricula demand a training intervention for pediatric educators. We demonstrated the successful implementation of a training workshop, with evidence of feasibility and generalizability, that addressed knowledge gaps and teaching and clinical skills.

A Case of Myelofibrosis and Myelodysplasia Identified Following Exposure to Isotretinoin.

A 15-year-old male individual treated with isotretinoin for acne vulgaris presented with persistent pancytopenia and circulating myeloblasts after discontinuation of the drug. Marrow assessment revealed myelofibrosis (MF) and myeloblasts exhibiting monosomy 7, diagnostic of myelodysplastic syndrome (MDS). Although a popular website seems to associate isotretinoin with MF, no published cases of MF or MDS attributable to this drug were identified. Although we expect that he would eventually have developed MDS and MF, this patient was perhaps identified sooner due to cytopenias accelerated by isotretinoin. This case illustrates that patients exhibiting cytopenias persisting following isotretinoin therapy merit evaluation for underlying hematopoietic disorders.

Building a Local Research Symposium: The Crossroads of Scholarship, Education, and Faculty Development.

Introduction: Demonstrating research productivity for faculty and trainees is challenging in primarily community-based settings, where academic, structural, and financial resources for faculty development in scholarship may be limited. More tools are needed to guide faculty leaders in community-based settings to develop opportunities locally. Methods: At our community-based children's hospital with recent academic affiliation and a new residency program, we developed an annual research symposium targeted to faculty and trainees. We refined tools for solicitation and scoring of abstracts, speaker selection, skill-building workshops, scholarly case report presentations, and a mentored poster session. We worked with available resources, kept costs flexible and low, and secured local partnerships to defray expenses. Evaluation consisted of session evaluations and trends in abstract submissions, institutional review board (IRB) submissions, and resident scholarly productivity over 4 years. Results: Scholarship improved over the symposium's first 4 years, with increased attendance (from 80 to 150), abstract submissions (from 29 to >50), IRB-approved research projects (from 65 to 123), and positive feedback on symposium evaluations. From our first three resident classes, 61 resident-authored abstracts were presented at our symposia, with 33 presented at regional and national meetings and 15 converted to peer-reviewed manuscripts. Discussion: We have developed a local research symposium to meet the needs of a new hospital's faculty and trainees. Evaluation data have allowed us to tailor the program to stakeholder needs. We provide a tool kit of generalizable resources for community-based programs to build on these efforts in a high-yield and cost-effective manner.

Teaching Conflict Resolution in Medicine: Lessons From Business, Diplomacy, and Theatre.

Introduction: Disagreement and conflict are inevitable among members of clinical teams, as well as with patients and families during the course of medical care. Despite the importance of physicians needing to negotiate and resolve conflicts, best practices for teaching these skills have not been established in a clinical setting. Methods: We developed teaching tools based on a conflict resolution model from the business world, emphasizing team dynamics and employing a structured, hierarchical approach to conflict resolution that preserves interpersonal relationships. We employed lessons from diplomacy and improvisational theatre to underscore nonverbal cues that improve communication during conflict. We prepared instructions for teaching conflict management and conflict resolution styles, small-group negotiations, case-based clinical scenarios, personal reflection, and facilitated debrief. The tools are customizable based on audience and available instructional time. Results: We implemented this resource for over 2 years with 20 pediatric residents and over 150 educators and fellows at national meetings. Participants reported that the topic was timely and important and identified the conflict resolution hierarchy, attention to conflict resolution styles, use of case-based discussion, and focus on nonverbal communication as effective and valuable elements. Discussion: This resource has been refined over five cycles of presentation and feedback with learners and educators. Our participants identified themes of conflicts in clinical settings that informed the case scenarios presented here, including interdisciplinary conflicts, ethical conflicts, and conflicts among members of the educational hierarchy. These tools are designed to meet established national educational priorities related to communication and professionalism across the educational continuum.

Neck Rhabdoid Tumors: Clinical Features and Consideration of Autologous Stem Cell Transplant.

Extrarenal malignant rhabdoid tumors (MRT) have a poor prognosis despite aggressive therapy. Adding high-dose chemotherapy with autologous stem cell rescue (HDC-ASCR) as consolidative therapy for MRT is controversial. We describe 2 patients, age 13 years and 19 months, with unresectable neck MRT. After chemotherapy and radiotherapy, both underwent HDC-ASCR and remain in remission over 4 years later. We reviewed all published cases of neck MRT, and found poorer outcomes and more variable age of presentation and time to progression than MRT at other sites. Neck MRT may represent a higher-risk subset of MRT, and addition of HDC-ASCR merits consideration.

Brachyury drives formation of a distinct vascular branchpoint critical for fetal-placental arterial union in the mouse gastrula.

How the fetal-placental arterial connection is made and positioned relative to the embryonic body axis, thereby ensuring efficient and directed blood flow to and from the mother during gestation, is not known. Here we use a combination of genetics, timed pharmacological inhibition in living mouse embryos, and three-dimensional modeling to link two novel architectural features that, at present, have no status in embryological atlases. The allantoic core domain (ACD) is the extraembryonic extension of the primitive streak into the allantois, or pre-umbilical tissue; the vessel of confluence (VOC), situated adjacent to the ACD, is an extraembryonic vessel that marks the site of fetal-placental arterial union. We show that genesis of the fetal-placental connection involves the ACD and VOC in a series of steps, each one dependent upon the last. In the first, Brachyury (T) ensures adequate extension of the primitive streak into the allantois, which in turn designates the allantoic-yolk sac junction. Next, the streak-derived ACD organizes allantoic angioblasts to the axial junction; upon signaling from Fibroblast Growth Factor Receptor-1 (FGFR1), these endothelialize and branch, forming a sprouting VOC that unites the umbilical and omphalomesenteric arteries with the fetal dorsal aortae. Arterial union is followed by the appearance of the medial umbilical roots within the VOC, which in turn designate the correct axial placement of the lateral umbilical roots/common iliac arteries. In addition, we show that the ACD and VOC are conserved across Placentalia, including humans, underscoring their fundamental importance in mammalian biology. We conclude that T is required for correct axial positioning of the VOC via the primitive streak/ACD, while FGFR1, through its role in endothelialization and branching, further patterns it. Together, these genetic, molecular and structural elements safeguard the fetus against adverse outcomes that can result from vascular mispatterning of the fetal-placental arterial connection.

STELLA collaborates in distinct mesendodermal cell subpopulations at the fetal-placental interface in the mouse gastrula.

The allantois-derived umbilical component of the chorio-allantoic placenta shuttles fetal blood to and from the chorion, thereby ensuring fetal-maternal exchange. The progenitor populations that establish and supply the fetal-umbilical interface lie, in part, within the base of the allantois, where the germ line is claimed to segregate from the soma. Results of recent studies in the mouse have reported that STELLA (DPPA-3, PGC7) co-localizes with PRDM1 (BLIMP1), the bimolecular signature of putative primordial germ cells (PGCs) throughout the fetal-placental interface. Thus, if PGCs form extragonadally within the posterior region of the mammal, they cannot be distinguished from the soma on the basis of these proteins. We used immunohistochemistry, immunofluorescence, and confocal microscopy of the mouse gastrula to co-localize STELLA with a variety of gene products, including pluripotency factor OCT-3/4, mesendoderm-associated T and MIXl1, mesendoderm- and endoderm-associated FOXa2 and hematopoietic factor Runx1. While a subpopulation of cells localizing OCT-3/4 was always found independently of STELLA, STELLA always co-localized with OCT-3/4. Despite previous reports that T is involved in specification of the germ line, co-localization of STELLA and T was detected only in a small subset of cells in the base of the allantois. Slightly later in the hindgut lip, STELLA+/(OCT-3/4+) co-localized with FOXa2, as well as with RUNX1, indicative of definitive endoderm and hemangioblasts, respectively. STELLA was never found with MIXl1. On the basis of these and previous results, we conclude that STELLA identifies at least five distinct cell subpopulations within the allantois and hindgut, where they may be involved in mesendodermal differentiation and hematopoiesis at the posterior embryonic-extraembryonic interface. These data provide a new point of departure for understanding STELLA's potential roles in building the fetal-placental connection.

Bad News Deserves Better Communication: A Customizable Curriculum for Teaching Learners to Share Life-Altering Information in Pediatrics.

INTRODUCTION: Learners have repeatedly expressed a desire for more structured training in communicating with families, especially when sharing life-altering information and breaking bad news. Concurrently, parents have indicated that pediatricians could conduct difficult conversations with greater skill. Based on local needs assessments and available pediatric literature, this guide presents didactic materials and a workshop-style, case-based, longitudinal approach for teaching communication skills to learners in pediatrics. METHODS: The customizable guide can be implemented as a 1-hour didactic presentation, a 1- to 3-hour workshop, or an integrated longitudinal curriculum. Unlike other available resources for breaking bad news, this guide is specifically designed for pediatrics and uses evidence-based communication guidelines developed for pediatric settings. The guidelines are modified from the adult-centered SPIKES (setting, perception, involvement, knowledge, emotions, summary) approach. The material was created by clinicians, educators, and parents of pediatric patients. In addition to video-based didactic materials and pediatric case scenarios, the guide includes materials for assessment, evaluation, and personal reflection. RESULTS: The modified SPIKES approach and didactic portion of this resource were validated as an initial training tool, yielding significant improvements in self-efficacy of pediatric providers and learners. Evaluations of the role-playing components provided by pediatric residents and fellows have been positive for the format and value of the learning experience. Participants reported a particular benefit from the inclusion of parent perspectives. DISCUSSION: Without a formal communication curriculum, learners must rely on chance observation of life-altering conversations during clinical rotations. This guide provides pediatric educators with structured, evidence-based materials to teach advanced communication skills.

Sharing life-altering information: development of pediatric hospital guidelines and team training.

UNLABELLED: Abstract Background: Despite parent and physician reports of inadequate skill development, there are few guidelines for training the pediatric care team in sharing life-altering information (SLAI), i.e., "breaking bad news." The necessary skills for SLAI differ between pediatric and adult medical environments. OBJECTIVES: We set out to establish evidence-based guidelines and multidisciplinary team training for SLAI in pediatrics, and to demonstrate an improvement in immediate self-efficacy of training participants. METHODS: A multidisciplinary task force, which included parent participation and feedback, and which received input from parents of patients in multiple pediatric subspecialties, crafted children's hospitalwide guidelines for SLAI. A one-hour training module on the guidelines was presented to several multidisciplinary pediatric team audiences; 159 voluntary pre- and post-presentation self-efficacy surveys were collected. Responses were analyzed by paired t-test (within groups) and ANOVA (between groups). RESULTS: All evaluated groups of care team members reported significant improvements in self-efficacy among four learning objectives after the training. Medical trainees, newer physicians, and nonphysician (e.g., midlevel providers including nurses) team members reported the greatest improvements, regardless of whether they had received previous training in SLAI. CONCLUSIONS: We propose pediatric-focused SLAI guidelines based on a modified SPIKES protocol. Focus on patient- and family-centered, culturally sensitive pediatric practices should be the basis for development of training that can be periodically reinforced. Future comprehensive training will incorporate experiential learning. SLAI requires a skill set that benefits from lifelong learning.

Mixl1 localizes to putative axial stem cell reservoirs and their posterior descendants in the mouse embryo.

Mixl1 is thought to play important roles in formation of mesoderm and endoderm. Previously, Mixl1 expression was reported in the posterior primitive streak and allantois, but the precise spatiotemporal whereabouts of Mixl1 protein throughout gastrulation have not been elucidated. To localize Mixl1 protein, immunohistochemistry was carried out at 2-4 h intervals on mouse gastrulae between primitive streak and 16-somite pair (s) stages (~E6.5-9.5). Mixl1 localized to the entire primitive streak early in gastrulation. However, by headfold stages (~E7.75-8.0), Mixl1 diminished within the mid-streak but remained concentrated at either end of the streak, and localized throughout midline posterior visceral endoderm. At the streak's anterior end, Mixl1 was confined to the posterior crown cells of Hensen's node, which contribute to dorsal hindgut endoderm, and the posterior notochord. In the posterior streak, Mixl1 localized to the Allantoic Core Domain (ACD), which is the source of most of the allantois and contributes to the posterior embryonic-extraembryonic interface. In addition, Mix1 co-localized with the early hematopoietic marker, Runx1, in the allantois and visceral yolk sac blood islands. During hindgut invagination (4-16s, ~E8.5-9.5), Mixl1 localized to the hindgut lip, becoming concentrated within the midline anastomosis of the splanchnopleure, which appears to create the ventral component of the hindgut and omphalomesenteric artery. Surrounding the distal hindgut, Mixl1 identified midline cells within tailbud mesoderm. Mixl1 was also found in the posterior notochord. These findings provide a critical systematic, and tissue-level understanding of embryonic Mixl1 localization, and support its role in regulation of crucial posterior axial mesendodermal stem cell niches during embryogenesis.

Neuronal leucine-rich repeat 6 (XlNLRR-6) is required for late lens and retina development in Xenopus laevis.

Leucine-rich repeat proteins expressed in the developing vertebrate nervous system comprise a complex, multifamily group, and little is known of their developmental function in vivo. We have identified a novel member of this group in Xenopus laevis, XlNLRR-6, and through sequence and phylogenetic analysis, have placed it within a defined family of vertebrate neuronal leucine-rich repeat proteins (NLRR). XlNLRR-6 is expressed in the developing nervous system and tissues of the eye beginning at the neural plate stage, and expression continues throughout embryonic and larval development. Using antisense morpholino oligonucleotide (MO) -mediated knockdown of XlNLRR-6, we demonstrate that this protein is critical for development of the lens, retina, and cornea. Reciprocal transplantation of presumptive lens ectoderm between MO-treated and untreated embryos demonstrate that XlNLRR-6 plays autonomous roles in the development of both the lens and retina. These findings represent the first in vivo functional analysis of an NLRR family protein and establish a role for this protein during late differentiation of tissues in the developing eye.

Early regeneration genes: Building a molecular profile for shared expression in cornea-lens transdifferentiation and hindlimb regeneration in Xenopus laevis.

Recent studies in Xenopus laevis have begun to compare gene expression during regeneration with that of the original development of specific structures (e.g., the hindlimb and lens), while other studies have sought differences in gene expression between regeneration-competent and regeneration-incompetent stages. To determine whether there are any similarities between the regeneration of different structures, we have used a differential screen to seek shared early gene expression between hindlimb regeneration and cornea-lens transdifferentiation in the Xenopus tadpole. We have isolated 13 clones representing genes whose expression is up-regulated within the first few days of both regenerating processes and which are not demonstrably up-regulated in the context of basic wound healing. Furthermore, all of these genes also show prominent late embryonic expression. The expression patterns and putative identities of all 13 genes are presented, and a model is considered that allows us to characterize and profile important changes in gene expression, which might be shared among various regenerating and developmental systems.

Molecular profiling: gene expression reveals discrete phases of lens induction and development in Xenopus laevis.

PURPOSE: Experimental tissue transplant studies reveal that lens development is directed by a series of early and late inductive interactions. These interactions impart a growing lens-forming bias within competent presumptive lens ectoderm that leads to specification and the commitment to lens fate. Relatively few genes are known which control these events. Identification of additional genes expressed during lens development may reveal key players in these processes and help to characterize these tissue properties. METHODS: A large suite of genes has been isolated that are expressed during the process of cornea-lens transdifferentiation (lens regeneration) in Xenopus laevis. Many of these genes are also expressed during embryonic lens development. Genes were selected for expression analysis via in situ hybridization. This group consisted of clones with possible roles in cell determination and differentiation as well as novel clones without previous identities. The spatiotemporal expression of these genes in conjunction with previously described genes were correlated with key events during embryonic lens formation. RESULTS: Eighteen of the thirty clones analyzed via in situ hybridization demonstrated observable expression in the developing lens. These genes were initially expressed in the presumptive lens ectoderm at a variety of timepoints throughout development. Expression is restricted to discrete time intervals during lens development. However, in most cases, expression was maintained throughout lens development after being initially upregulated. CONCLUSIONS: The expression of these genes suggests that a genetic hierarchy exists in which an increasing number of genes are upregulated and their expression is maintained throughout lens development. Suites of genes appear to be upregulated at specific timepoints during development, correlating with stages of lens induction, specification, commitment, lens placode formation, and lens differentiation, while suites at additional timepoints suggest that other, previously unreported stages exist as well. This analysis provides a genetic framework for characterizing these processes of lens development.

Characterizing gene expression during lens formation in Xenopus laevis: evaluating the model for embryonic lens induction.

Few directed searches have been undertaken to identify the genes involved in vertebrate lens formation. In the frog Xenopus, the larval cornea can undergo a process of transdifferentiation to form a new lens once the original lens is removed. Based on preliminary evidence, we have shown that this process shares many elements of a common molecular/genetic pathway to that involved in embryonic lens development. A subtracted cDNA library, enriched for genes expressed during cornea-lens transdifferentiation, was prepared. The similarities/identities of specific clones isolated from the subtracted cDNA library define an expression profile of cells undergoing cornea-lens transdifferentiation ("lens regeneration") and corneal wound healing (the latter representing a consequence of the surgery required to trigger transdifferentiation). Screens were undertaken to search for genes expressed during both transdifferentiation and embryonic lens development. Significantly, new genes were recovered that are also expressed during embryonic lens development. The expression of these genes, as well as others known to be expressed during embryonic development in Xenopus, can be correlated with different periods of embryonic lens induction and development, in an attempt to define these events in a molecular context. This information is considered in light of our current working model of embryonic lens induction, in which specific tissue properties and phases of induction have been previously defined in an experimental context. Expression data reveal the existence of further levels of complexity in this process and suggests that individual phases of lens induction and specific tissue properties are not strictly characterized or defined by expression of individual genes.