Pediatric contributions and lessons learned from the NEPTUNE cohort study.

Primary glomerular diseases are rare entities. This has hampered efforts to better understand the underlying pathobiology and to develop novel safe and effective therapies. NEPTUNE is a rare disease network that is focused on patients of all ages with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. It is a longitudinal cohort study that collects detailed demographic, clinical, histopathologic, genomic, transcriptomic, and metabolomic data. The goal is to develop a molecular classification for these disorders that supersedes the traditional pathological features-based schema. Pediatric patients are important contributors to this ongoing project. In this review, we provide a snapshot of the children and adolescents enrolled in NEPTUNE and summarize some key observations that have been made based on the data accumulated during the study. In addition, we describe the development of NEPTUNE Match, a program that aims to leverage the multi-scalar information gathered for each individual patient to provide guidance about potential clinical trial participation based on the molecular characterization and non-invasive biomarker profile. This represents the first organized effort to apply principles of precision medicine to the treatment of patients with primary glomerular disease. NEPTUNE has proven to be an invaluable asset in the study of glomerular diseases in patients of all ages including children and adolescents.

Dissemination, Utilization, and Satisfaction With Emergency Medicine Resident Simulation Curriculum for Pediatrics (EM ReSCu Peds) by North American Residency Programs.

OBJECTIVES: Our research team's primary objective was to investigate how a custom standard simulation curriculum for teaching emergency medicine residents about pediatrics was being used by programs across North America. We also wanted to know if program directors were satisfied with the curriculum and whether they had challenges with implementing it. Our long-term goal is to promote the Emergency Medicine Resident Simulation Curriculum for Pediatrics for use by all programs in the United States. METHODS: We distributed an electronic questionnaire to individuals who have downloaded the Emergency Medicine Resident Simulation Curriculum for Pediatrics in the form of an e-book from the Academic Life in Emergency Medicine Web site. The curriculum was marketed through national emergency medicine (EM) and pediatric emergency medicine (PEM) groups, PEM listserv, and through the International Network for Simulation-Based Pediatric Innovation, Research, and Education. We asked survey recipients how they used the curriculum, plans for future maintenance, satisfaction with curriculum use, and whether they had any challenges with implementation. Finally, we asked demographic questions. RESULTS: Most survey respondents were EM or PEM health care physicians in the United States or Canada. Respondents' primary goal of using the curriculum was resident education. Through assessment with the Net Promoter Score, satisfaction with the curriculum was net positive with users largely scoring as curriculum promoters. We found COVID-19 and overall time limitations to be implementation barriers, whereas learner interest in topics was the largest cited facilitator. Most responders plan to continue to implement either selected cases or the entire curriculum in the future. CONCLUSIONS: Of those who responded, our target audience of EM physicians used our curriculum the most. Further investigation on implementation needs, specifically for lower resource emergency programs, is needed.

A knockout-first model of H3f3a gene targeting leads to developmental lethality.

Histone variant H3.3 is encoded by two genes, H3f3a and H3f3b, which can be expressed differentially depending on tissue type. Previous work in our lab has shown that knockout of H3f3b causes some neonatal lethality and infertility in mice, and chromosomal defects in mouse embryonic fibroblasts (MEFs). Studies of H3f3a and H3f3b null mice by others have produced generally similar phenotypes to what we found in our H3f3b nulls, but the relative impacts of the loss of either H3f3a or H3f3b have varied depending on the approach and genetic background. Here we used a knockout-first approach to target the H3f3a gene for inactivation in C57BL6 mice. Homozygous H3f3a targeting produced a lethal phenotype at or before birth. E13.5 null embryos had some potential morphological differences from WT littermates including smaller size and reduced head size. An E18.5 null embryo was smaller than its control littermates with several potential defects including small head and brain size as well as small lungs, which would be consistent with a late gestation lethal phenotype. Despite a reduction in H3.3 and total H3 protein levels, the only histone H3 post-translational modification in the small panel assessed that was significantly altered was the unique H3.3 mark phospho-Serine31, which was consistently increased in null neurospheres. H3f3a null neurospheres also exhibited consistent gene expression changes including in protocadherins. Overall, our findings are consistent with the model that there are differential, cell-type-specific contributions of H3f3a and H3f3b to H3.3 functions in epigenetic and developmental processes.

Algorithms for Treating Dyslipidemia in Youth.

PURPOSE OF REVIEW: The goal of this article is to review algorithms for treating dyslipidemia in youth, discuss pitfalls, propose enhanced algorithms to address pitfalls, and consider future directions. RECENT FINDINGS: The presence of modifiable and non-modifiable cardiovascular disease (CVD) risk factors during childhood is associated with CVD-related events in adulthood. Recent data has shown that childhood initiation of statin therapy in youth < 18 years of age with familial hypercholesterolemia reduces the risk of adult CVD. However, pediatric dyslipidemia remains undertreated in part due to a lack of primary health care providers with adequate understanding of screening guidelines and pediatric lipidologists with experience in treatment and follow-up of this unique population. Management algorithms have been published by the National Heart, Lung, and Blood Institute and American Heart Association as tools to empower clinicians to manage dyslipidemia. We propose enhanced algorithms, which incorporate recently approved pharmacotherapy to address the management gaps. Future algorithms based upon clinical risk scores may enhance treatment and improve outcomes. Algorithms for dyslipidemia management which target youth < 18 years of age are tools which empower clinicians to manage dyslipidemia in this unique population. Enhanced algorithms may help address pitfalls. We acknowledge the need for further risk assessment tools in pediatrics for tailored dyslipidemia management.

Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology.

BACKGROUND: Failure of the glomerular filtration barrier, primarily by loss of slit diaphragm architecture, underlies nephrotic syndrome in minimal change disease. The etiology remains unknown. The efficacy of B cell-targeted therapies in some patients, together with the known proteinuric effect of anti-nephrin antibodies in rodent models, prompted us to hypothesize that nephrin autoantibodies may be present in patients with minimal change disease. METHODS: We evaluated sera from patients with minimal change disease, enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) cohort and from our own institutions, for circulating nephrin autoantibodies by indirect ELISA and by immunoprecipitation of full-length nephrin from human glomerular extract or a recombinant purified extracellular domain of human nephrin. We also evaluated renal biopsies from our institutions for podocyte-associated punctate IgG colocalizing with nephrin by immunofluorescence. RESULTS: In two independent patient cohorts, we identified circulating nephrin autoantibodies during active disease that were significantly reduced or absent during treatment response in a subset of patients with minimal change disease. We correlated the presence of these autoantibodies with podocyte-associated punctate IgG in renal biopsies from our institutions. We also identified a patient with steroid-dependent childhood minimal change disease that progressed to end stage kidney disease; she developed a massive post-transplant recurrence of proteinuria that was associated with high pretransplant circulating nephrin autoantibodies. CONCLUSIONS: Our discovery of nephrin autoantibodies in a subset of adults and children with minimal change disease aligns with published animal studies and provides further support for an autoimmune etiology. We propose a new molecular classification of nephrin autoantibody minimal change disease to serve as a framework for instigation of precision therapeutics for these patients.

The Role of Non-statin Lipid-Lowering Medications in Youth with Hypercholesterolemia.

PURPOSE OF REVIEW: Lifestyle modification is additive to lipid-lowering medications in the treatment of heterozygous familial hypercholesterolemia (HeFH), which does not respond sufficiently to statin therapy. While both are also important in homozygous familial hypercholesterolemia (HoFH), additional measures such as apheresis may be needed. The purpose of this review is to identify non-statin medications to lower cholesterol that are available for children and adolescents as adjunctive therapy. RECENT FINDINGS: Ezetimibe is commonly used as second-line pharmacotherapy for treatment of HeFH and HoFH. Colesevelam, a bile acid sequestrant, may be considered for adjunct therapy. Since 2015, the PCSK9 inhibitor evolocumab has been available for adolescents, and its FDA approval has now expanded to age 10 years. The ANGPTL3 inhibitor evinacumab has been approved for children age 12 years and older. A clinical trial for lomitapide is in progress. Approvals for PCSK9 and ANGPTL3 inhibitors have expanded opportunities for children and adolescents with HeFH and HoFH to achieve lower LDL-C levels.

Case-Control Study of Individuals with Discrepant Nucleocapsid and Spike Protein SARS-CoV-2 IgG Results.

BACKGROUND: Laboratory-based methods for SARS-CoV-2 antibody detection vary widely in performance. However, there are limited prospectively-collected data on assay performance, and minimal clinical information to guide interpretation of discrepant results. METHODS: Over a 2-week period, 1080 consecutive plasma samples submitted for clinical SARS-CoV-2 IgG testing were tested in parallel for anti-nucleocapsid IgG (anti-N, Abbott) and anti-spike IgG (anti-S1, EUROIMMUN). Chart review was conducted for samples testing positive or borderline on either assay, and for an age/sex-matched cohort of samples negative by both assays. CDC surveillance case definitions were used to determine clinical sensitivity/specificity and conduct receiver operating characteristics curve analysis. RESULTS: There were 52 samples positive by both methods, 2 positive for anti-N only, 34 positive for anti-S1 only, and 27 borderline for anti-S1. Of the 34 individuals positive for anti-S1 alone, 8 (24%) had confirmed COVID-19. No anti-S1 borderline cases were positive for anti-N or had confirmed/probable COVID-19. The anti-N assay was less sensitive (84.2% [95% CI 72.1-92.5%] vs 94.7% [95% CI 85.4-98.9%]) but more specific (99.2% [95% CI 95.5-100%] vs 86.9% [95% CI 79.6-92.3%]) than anti-S1. Abbott anti-N sensitivity could be improved to 96.5% with minimal effect on specificity if the index threshold was lowered from 1.4 to 0.6. CONCLUSION: Real-world concordance between different serologic assays may be lower than previously described in retrospective studies. These findings have implications for the interpretation of SARS-CoV-2 IgG results, especially with the advent of spike antigen-targeted vaccination, as a subset of patients with true infection are anti-N negative and anti-S1 positive.

Venous Thoracic Outlet Syndrome in a Young Student.

BACKGROUND: Venous thoracic outlet syndrome (VTOS) results from compression and thrombosis of the axillosubclavian vein. In primary effort thrombosis, a subtype of VTOS, chronic repetitive compression injury of the axillosubclavian vein leads to scarring, stenosis, and eventually, thrombosis. This is a rare manifestation of an upper extremity deep vein thrombosis. CASE REPORT: A 23-year-old male student without significant past medical history presented to our Emergency Department with a complaint of intermittent swelling and discoloration of his upper right arm. His symptoms had been present for the past year and had worsened over the past few weeks. Swelling was associated with overhead use of the arm. There is no family history of clotting disorders. A computed tomography angiogram of the chest with upper extremity runoff showed findings consistent with VTOS. The patient was discharged with an urgent referral to Vascular Surgery. Within 2 weeks, he underwent multiple surgical procedures and was initiated on anticoagulation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: VTOS usually presents in patients who do not have commonly recognized prothrombotic risk factors. Emergency physicians should include this diagnosis in their differential because good functional outcomes rely on early diagnosis and prompt initiation of treatment. In addition, emergency physicians must refer these patients to vascular surgeons, as most will require surgical management.

Effects of Hepatic Ischemia-Reperfusion Injuries and NRF2 on Transcriptional Activities of Bile Transporters in Rats.

BACKGROUND: The effect of hepatic ischemia-reperfusion injury (IRI) on bile transporter (BT) gene expression is unknown. We hypothesized that abnormal expression of BTs during hepatic IRI is dependent on nuclear factor erythroid 2-related factor 2 (NRF2), which contributes to the cholestasis after reperfusion. METHODS: Sham surgery and short (60 min) or long (90 min) periods of warm ischemia time (WIT) with or without reperfusion for 24 h were applied to wild-type Sprague-Dawley rats and Nrf2 knockout rats (n = 5 per group). At each stage of IRI, the serum levels of aminotransferase, total bilirubin, and bile acids were measured. In addition, hepatic tissue was sampled to determine the histologic score of IRI (Suzuki score), measure adenosine triphosphate (ATP), and identify the quantitative real-time polymerase chain reactions of BTs (Oatp1, Ntcp, Mrp2, Bsep, and Mrp3). RESULTS: In short periods of WIT, BT expression increased during the ischemia stage and returned to the baseline after reperfusion. However, in long periods of WIT, BT expression did not increase after ischemia and decreased further after reperfusion. Short WIT did not increase BT expression in Nrf2 knockout animals. The level of BT expression was correlated with the Suzuki score, the serum levels of aminotransferase, bilirubin, and bile acids, and tissue ATP level. Stepwise multiple regression analysis derived equations to predict the Suzuki score (R2 = 76.8, P < 0.001), serum total bilirubin (R2 = 61.2, P < 0.001), and tissue ATP (R2 = 61.1, P < 0.001). CONCLUSIONS: Short WIT induces the transcriptional activities of BT, whereas long WIT depresses them, and the effect was blunted by Nrf2 knockout status. BT expression can be considered a surrogate marker for hepatic IRI.

Testosterone protects high-fat/low-carbohydrate diet-induced nonalcoholic fatty liver disease in castrated male rats mainly via modulating endoplasmic reticulum stress.

We previously showed that testosterone (T) deficiency enhanced high-fat/low-carbohydrate diet (HFD)-induced hepatic steatosis in rats independent of insulin resistance and that T replacement reduced hepatic macrovesicular fat accumulation and inflammation. The present report explores the mechanism of T's protective effects on HFD-induced steatohepatitis. Adult male rats were randomized into four treatment groups for 15 wk: intact rats on regular chow diet or HFD, and castrated rats on HFD with or without T replacement. Fatty acid ß-oxidation and de novo synthesis were not changed by castration and T replacement, but expression of lipid export proteins ApoB100 and microsomal triglyceride transfer protein (MTP) was suppressed by HFD in both intact and castrated rats but restored by T replacement. Macrovesicular lipid droplet-related proteins perilipin 1 and fat-specific protein 27 were increased by HFD in castrated rats and suppressed by T replacement. Higher activation/expression of ER stress proteins (PERK, IRE-1α, JNK, NF-κB, and CHOP) was demonstrated in castrated rats fed HFD compared with intact animals, and T replacement suppressed these changes. We conclude that 1) HFD leads to ApoB100/MTP suppression reducing export of lipids; 2) castration promotes progression to steatohepatitis through activation of the ER stress pathway and enhancement of macrovesicular droplet protein expression; and 3) testosterone suppresses ER stress, inhibits the formation of macrovesicular lipid droplets, promotes lipid export, and ameliorates steatohepatitis induced by HFD and castration.

Blood cadmium by race/hispanic origin: The role of smoking.

BACKGROUND: There have been increasing concerns over health effects of low level exposure to cadmium, especially those on bones and kidneys. OBJECTIVE: To explore how age-adjusted geometric means of blood cadmium in adults varied by race/Hispanic origin, sex, and smoking status among U.S. adults and the extent to which the difference in blood cadmium by race/Hispanic origin and sex may be explained by intensity of smoking, a known major source of cadmium exposure. METHODS: Our sample included 7,368 adults from National Health and Nutrition Examination Survey (NHANES) 2011-2014. With direct age adjustment, geometric means of blood cadmium and number of cigarettes smoked per day were estimated for subgroups defined by race/Hispanic origin, smoking status, and sex using interval regression, which allows mean estimation in the presence of left- and right-censoring. RESULTS: Among never and former smoking men and women, blood cadmium tended to be higher for non-Hispanic Asian adults than adults of other race/Hispanic origin. Among current smokers, who generally had higher blood cadmium than never and former smokers, non-Hispanic white, black, and Asian adults had similarly elevated blood cadmium compared to Hispanic adults. A separate analysis revealed that non-Hispanic white adults tended to have the highest smoking intensity regardless of sex, than adults of the other race/Hispanic origin groups. CONCLUSIONS: The observed pattern provided evidence for smoking as a major source of cadmium exposure, yet factors other than smoking also appeared to contribute to higher blood cadmium of non-Hispanic Asian adults.

Septic Abortion Complicated by Disseminated Intravascular Coagulation.

Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of two concurrent conditions: septic abortion and disseminated intravascular coagulation (DIC). Introduction: Patients with an abortion (spontaneous or induced) of less than twenty weeks gestation may present with concurrent uterine infection, also known as septic abortion. One of the complications of septic abortion is DIC. Early management of both underlying etiology (septic abortion) and subsequent complications (DIC) is crucial to minimize morbidity and mortality. Educational Objectives: At the conclusion of the simulation session, learners will be able to: 1) Obtain a relevant focused history including pregnancy history, medication use, and past medical history. 2) Develop a differential for fever and vaginal bleeding in a pregnant patient. 3) Discuss management of septic abortion, including empiric broad-spectrum antibiotics and obstetric consultation for source control with dilation and curettage (D&C). 4) Discuss expected laboratory findings of disseminated intravascular coagulation (DIC). 5) Discuss management of DIC, including identification of underlying etiology and supportive resuscitation with blood products. 6) Review the components of blood products. 7) Identify appropriate disposition of the patient to the intensive care unit (ICU). Educational Methods: This session was conducted using high-fidelity simulation followed by a debriefing session and discussion about the diagnosis, differential, and management of both septic abortion and DIC. Debriefing methods may be left to the discretion of participants, but the authors have utilized advocacy-inquiry techniques. In this technique, the facilitator described something they observed in the case, outlined their reasoning as a facilitator why this observation was important or why they had questions, and then asked the learners to share their frame of reference at the time. An example: "I heard the team leader state that the platelets were normal, but then another resident disagreed. No one paused to come to a consensus. I'm wondering why this wasn't explored further in real time. Tell me more." This scenario may also be run as an oral boards case or adapted for other learners such as critical care fellows. Research Methods: Our residents were provided a survey at the completion of the debriefing session so they could rate different aspects of the simulation, as well as provide qualitative feedback on the scenario. The local institution's simulation center's electronic feedback form is based on the Center of Medical Simulation's Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form,1 with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. Results: Thirteen learners completed a feedback form out of seventeen participants. This session received all six and seven scores (consistently effective/very good and extremely effective/outstanding, respectively) other than two isolated 4 scores. Discussion: This is a cost-effective method for reviewing septic abortion and DIC. The case may be modified for appropriate audiences, such as simplifying the case to septic abortion without DIC. You can also consider not showing an initial temperature with the initial set of vitals unless it is specifically asked for by the participants. We encourage readers to utilize bleeding moulage techniques as a visual stimulus to increase psychological buy-in. Topics: Medical simulation, septic abortion, pregnancy complications, hematology emergencies, obstetric emergencies, disseminated intravascular coagulation, emergency medicine.

Preparing interns for clinical practice through an institution-wide simulation-based mastery learning program for teaching central venous catheter placement.

Central venous catheter (CVC) placement is a challenging procedure with known iatrogenic risks. However, there are no residency program requirements to demonstrate baseline CVC procedural competency. Competency-based procedural education has been shown to decrease CVC-associated morbidity, but there has been limited literature about institution-wide efforts to ensure initial trainee competency for CVC placement. This study describes the implementation of a competency-based CVC curriculum for first-year interns across an institution before supervised clinical care. An institution-wide, simulation-based mastery training curriculum was designed to assess initial competency in CVC placement in first-year residents during 2021 and 2022. A checklist was internally developed with a multidisciplinary team. Using the Mastery-Angoff technique, minimum passing standards were derived to define competency levels considered appropriate for intern participation in supervised clinical care. Interns were trained through the competency-based program with faculty assessing intern performance using the CVC checklist to verify procedural competency. Over 2 academic cycles, 229 interns from 20 specialties/subspecialties participated. Overall, 83% of interns met performance standards on their first posttest attempt, 14% on the second attempt, and 3% on the third attempt. Interns from both cycles demonstrated significant improvement from baseline to posttest scores (P < .001). Overall, 10.5% of interns performed dangerous actions during assessment (malpositioning, retained guidewire, or carotid dilation). All interns ultimately achieved the passing standard to demonstrate initial competency in the simulation assessment. All participating interns demonstrated simulation-based competency allowing them to place CVCs under supervised clinical care. Dangerous actions, however, were not uncommon. Simulation-based teaching and learning frameworks were a feasible method to promote patient safety through an institutional-wide verification of preliminary procedural competency.

Diabetes screening outcomes in youth presenting for paediatric weight management: A report of the Paediatric Obesity Weight Evaluation Registry.

OBJECTIVE: Rising prevalence of obesity has led to increased rates of prediabetes and diabetes mellitus (DM) in children. This study compares rates of prediabetes and diabetes using two recommended screening tests (fasting plasma glucose [FPG] and haemoglobin A1c [HbA1c]). STUDY DESIGN: Data were collected prospectively from 37 multi-component paediatric weight management programs in POWER (Paediatric Obesity Weight Evaluation Registry). RESULTS: For this study, 3962 children with obesity without a known diagnosis of DM at presentation and for whom concurrent measurement of FPG and HbA1c were available were evaluated (median age 12.0 years [interquartile range, IQR 9.8, 14.6]; 48% males; median body mass index 95th percentile [%BMIp95] 134% [IQR 120, 151]). Notably, 10.7% had prediabetes based on FPG criteria (100-125 mg/dL), 18.6% had prediabetes based on HbA1c criteria (5.7%-6.4%), 0.9% had DM by FPG abnormality (≥126 mg/dL) and 1.1% had DM by HbA1c abnormality (≥6.5%). Discordance between the tests was observed for youth in both age groups (10-18 years [n = 2915] and age 2-9 years [n = 1047]). CONCLUSION: There is discordance between FPG and HbA1c for the diagnosis of prediabetes and DM in youth with obesity. Further studies are needed to understand the predictive capability of these tests for development of DM (in those diagnosed with prediabetes) and cardiometabolic risk.

A Drosophila model to screen Alport syndrome COL4A5 variants for their functional pathogenicity.

Alport syndrome is a hereditary chronic kidney disease, attributed to rare pathogenic variants in either of three collagen genes (COL4A3/4/5) with most localized in COL4A5. Trimeric type IV Collagen α3α4α5 is essential for the glomerular basement membrane that forms the kidney filtration barrier. A means to functionally assess the many candidate variants and determine pathogenicity is urgently needed. We used Drosophila, an established model for kidney disease, and identify Col4a1 as the functional homolog of human COL4A5 in the fly nephrocyte (equivalent of human podocyte). Fly nephrocytes deficient for Col4a1 showed an irregular and thickened basement membrane and significantly reduced nephrocyte filtration function. This phenotype was restored by expressing human reference (wildtype) COL4A5, but not by COL4A5 carrying any of three established pathogenic patient-derived variants. We then screened seven additional patient COL4A5 variants; their ClinVar classification was either likely pathogenic or of uncertain significance. The findings support pathogenicity for four of these variants; the three others were found benign. Thus, demonstrating the effectiveness of this Drosophila in vivo kidney platform in providing the urgently needed variant-level functional validation.

Acute ingestion of sugar-free red bull energy drink has no effect on upper body strength and muscular endurance in resistance trained men.

Consumption of energy drinks by both recreational and competitive athletes has increased dramatically in recent years. The primary ingredients in many energy drinks include caffeine (CAF) in various forms and taurine. The purpose of this randomized, double-blind, crossover study was to examine the effect of sugar-free (SF) Red Bull (RB) containing CAF and taurine to a CAF only drink and a SF CAF-free placebo (PL) on 1 repetition maximum (1RM) bench press (BP) and the volume load (VL; repetitions × kg at 70% 1RM) during one BP set to failure in experienced lifters. Seventeen college-age men randomly received the following: (A) 500 mL of SF-RB containing CAF (160 mg) and taurine (2000 mg); (B) 500 mL of a SF drink containing CAF only (160 mg); or (C) a SF CAF-free 500 mL PL drink 60 minutes before testing on 3 separate occasions. After a standard warm-up, the 1RM was determined for each subject and, after 5 minutes rest, they completed repetitions to failure at 70% of their 1RM to assess VL. Differences between trials for 1RM BP and the VL were identified using repeated measures analysis of variance (p < 0.05). The results indicated that neither SF-RB nor the CAF drink had any effect on 1RM BP (115.13 ± 16.19 kg and 114.87 ± 16.16 kg, respectively) or VL (1173.08 ± 170.66 kg and 1164.14 ± 147.03 kg, respectively) compared with PL (1RM = 114.07 ± 16.09 kg; VL = 1141.46 ± 193.41 kg). Although the CAF content in the energy drinks used in the present study was low (∼2.0 mg/kg), the finding of no effect of the CAF containing energy drinks for 1RM BP are in agreement with previous studies using intakes up to 6.0 mg/kg. These findings suggest that SF-RB has no effect on upper body 1RM strength or VL in resistance trained men.

Botulism due to Injection Drug Use.

Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of wound botulism secondary to injection drug use. Introduction: Botulism is a relatively rare cause of respiratory failure and descending weakness in the United States, caused by prevention of presynaptic acetylcholine release at the neuromuscular junction. This presentation has several mimics, including myasthenia gravis and the Miller-Fisher variant of Guillain-Barré. It may be caused by ingestion of spores (infant), ingestion of pre-formed toxin (food-borne), formation of toxin in vivo (wound-associated cases), through weaponized sources, or through inappropriately administered injections (iatrogenic). Cases of black tar heroin injection have been associated with botulism. Regardless of the etiology, prompt assessment and support of respiratory muscle strength and ordering antidotal therapy is key to halting further muscle weakness progression. Educational Objectives: At the conclusion of the simulation session, learners will be able to: 1) Identify the different etiologies of botulism, including wound, food-borne, infant, iatrogenic, and inhalational sources, 2) describe the pathophysiology of botulism toxicity and how it prevents presynaptic acetylcholine release at the neuromuscular junction, 3) develop a differential for bilateral descending muscle weakness, 4) compare and contrast presentations of myasthenia gravis, botulism, and the Miller-Fisher variant of Guillain-Barré syndrome, 5) describe measurement of neurologic respiratory parameter testing, such as negative inspiratory force, 6) outline treatment principles of wound-associated botulism, including antitoxin administration, wound debridement, tetanus vaccination, and evaluation for the need of antibiotics, and 7) identify appropriate disposition of the patient to the medical intensive care unit (ICU). Educational Methods: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on the diagnosis, differential diagnosis, and management of botulism secondary to injection drug use. Debriefing methods may be left to the discretion of participants, but the authors have utilized advocacy-inquiry techniques. This scenario may also be run as an oral board case. Research Methods: Our residents are provided a survey at the completion of the debriefing session so they may rate different aspects of the simulation, as well as provide qualitative feedback on the scenario. Results: Sixteen learners completed a feedback form. This session received all six and seven scores (consistently effective/very good and extremely effective/outstanding, respectively) other than three isolated five scores. The form also includes an area for general feedback about the case at the end. Illustrative examples of feedback include: "Really awesome debrief, breakdown of pathophysiology and clinical applications. Great work!"; "Great case with awesome learning points," and "Loved this session. Rare case but very great learning." Specific scores are available upon request. Discussion: This is a cost-effective method for reviewing botulism diagnosis and management. The case may be modified for appropriate audiences, such as using classic illness scripting (eg, ingestion of canned foods). We encourage readers to utilize a standardized patient to demonstrate extraocular muscle weakness and bulbar symptoms to increase psychological buy-in. Topics: Medical simulation, botulism, toxicologic emergencies, toxicology, neurology, emergency medicine.

Care of Transgender and Gender-Diverse Children and Adolescents.

Children and adolescents may present with transgender or gender diverse (TGD) identity during the course of development. Pediatricians may be the first health care providers to whom TGD identity is revealed. Pediatricians can optimize health care outcomes by promoting a gender-affirming clinical environment, initiating the evaluation for gender incongruence, supporting social transition, and initiating medical interventions. Clinical practice guidelines are available from the World Professional Association for Transgender Health (WPATH, Standards of Care, version 8, 2022) and the Endocrine Society (2017). This article outlines a general approach to providing social and medical affirming care from the pediatrician's office.

Ventricular Tachycardia.

Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of ventricular tachycardia (VT) that is refractory to single dose anti-arrhythmic management. Background: Electrical storm, defined as three or more episodes of sustained VT, ventricular fibrillation, or appropriate shocks from an implantable cardioverter defibrillator within 24 hours,1 has a mortality rate up to 14% in the first 48 hours.2 Ventricular tachycardia may present in a heterogenous fashion, not only with stable versus unstable clinical presentations, but also with different electrocardiographic morphologies and etiologies.1 Understanding how to rapidly diagnose, treat, and utilize second or third-line treatments is vital in the setting of refractory ventricular tachycardia rather than relying on the success of first-line agents. Appreciation for what medications are readily available in your crash cart and medication dispensing cabinet is critical for timely management for refractory ventricular tachycardia. Educational Objectives: At the conclusion of the simulation session, learners will be able to: 1) identify the different etiologies of VT, including structural heart disease, acute ischemia, and acquired or congenital QT syndrome; 2) describe confounding factors of VT, such as electrolyte abnormalities and sympathetic surge; 3) describe how to troubleshoot an unsuccessful synchronized cardioversion, including checking equipment connections, increasing delivered energy, and changing pad placement; 4) compare and contrast treatments of VT based on suspected underlying etiology; 5) describe reasons to activate the cardiac catheterization lab other than occlusive myocardial infarction; and 6) identify appropriate disposition of the patient to the cardiac catheterization lab. Educational Methods: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on the diagnosis, differential diagnosis, and management of VT. Debriefing methods may be left to the discretion of participants, but the authors have utilized advocacy-inquiry techniques. This scenario may also be run as an oral board case. Research Methods: Our residents are provided a survey at the completion of the debriefing session so they may rate different aspects of the simulation, as well as provide qualitative feedback on the scenario. Results: The local institution's simulation center's electronic feedback form is based on the Center of Medical Simulation's Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form3 with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. Twelve learners completed a feedback form. This session received 6 and 7 scores (consistently effective/very good and extremely effective/outstanding, respectively) other than three isolated 5 scores. The lowest average score was 6.67 for "Before the simulation, the instructor set the stage for an engaging learning experience." The highest average score was 7 for "The instructor helped me see how to improve or how to sustain good performance." The form also includes an area for general feedback about the case at the end. Illustrative examples of feedback include: "Excellent care and debrief." Specific scores are available upon request. Discussion: This is a cost-effective method for reviewing VT diagnosis and management. The case may be modified for appropriate audiences, such as describing what medications may be readily available in a free-standing emergency department or pre-hospital setting. Topics: Medical simulation, ventricular tachycardia, cardiac emergencies, dysrhythmias, cardiology, emergency medicine.

Inhalational Injury Secondary to House Fire.

Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of patients with an inhalational airway injury secondary to a house fire. Background: Burn injuries are a common occurrence encountered by the emergency physician. According to the National Hospital Ambulatory Medical Care Survey, around 371,000 patients were treated in emergency departments for fire or burn injuries across the United States in 2020. This represents around 1% of emergency department visits related to injury, poisoning, or adverse effects.1 One of the most dangerous and time critical aspects of managing severely burned patients is inhalation injury. Inhalation injury is a relatively vague term which may refer to pulmonary exposure to a wide range of chemicals in various forms. In the context of burn patients, this is most often smoke exposure. It is critical that the emergency medicine provider rapidly identifies the potential for an inhalational injury in order to determine the need for definitive airway management. It is also important that the provider has the necessary skills and systematic approach to manage what is likely to be a difficult airway. Furthermore, providers must then have the knowledge of how to best manage and resuscitate these severely burned patients post-intubation. Educational Objectives: At the conclusion of the simulation session, learners will be able to: 1) recognize the indications for intubation in a thermal burn/inhalation injury patient; 2) develop a systematic approach to an inhalational injury airway; and 3) recognize indications for transfer to burn center. Educational Methods: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on the diagnosis, differential diagnosis, and management of inhalational airway injury secondary to a house fire. Debriefing methods may be left to the discretion of participants, but the authors have utilized advocacy-inquiry techniques. This scenario may also be run as an oral board case. Research Methods: Our residents are provided a survey at the completion of the debriefing session so they may rate different aspects of the simulation, as well as provide qualitative feedback on the scenario. The local institution's simulation center's electronic feedback form is based on the Center of Medical Simulation's Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form2 with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. Results: Nine learners completed a feedback form. This session received all 6 & 7 scores (consistently effective/very good and extremely effective/outstanding, respectively) other than one isolated 5 score. Discussion: This is a cost-effective method for reviewing inhalational airway injury diagnosis and management. The case may be modified for targeted audiences, expected resources, and learning objectives, such as removal of a bronchoscope availability in settings which are expected to be resource-limited. Some readers may choose to focus on other aspects of burn management instead of airway securement such as cyanide and/or carbon monoxide toxicity. We encourage readers to limit the number of learning objectives because airway algorithms and troubleshooting for this scenario was a rich, stand-alone debriefing. There was not enough time to review in detail all nuanced aspects of the burned patient, including: Lund-Browder versus rule of 9's, modified Brooke versus Parkland formulas, indications for and completion of escharotomies, and/or identification and treatment of cyanide and carbon monoxide toxicity. Topics: Medical simulation, burns, airway emergencies, emergency medicine.