This piece was written with the phrases that have been said to me or to other female colleagues throughout my year of clinical rotations. Although women in medicine have come a long way, I want this to illustrate the pain that is still inflicted towards female professionals through words like these.
This original orchestral composition paints the story of a father and his emotional journey from the moment his baby girl is born through her early childhood to the diagnosis of an abrupt and serious disease.
Gabrielle L. Brumfield, Shelby M. Knoche, Alaina C. Larson, Brittany Poelaert, Benjamin T. Goetz, Poomy Pandey, Don W. Coulter, and Joyce C. Solheim
Background: Neuroblastoma is the third most common childhood cancer and accounts for 12% of cancer-associated deaths in children under the age of 15. Patients with high risk neuroblastoma have a poor 5-year survival rate of less than 50%. Neuroblastoma tumors treated with the histone deacetylase inhibitor (HDACi) vorinostat have increased infiltration of macrophages with upregulated immune cell-surface receptors. Neuroblastoma cells release VEGF and M-CSF, which may alter intratumoral macrophage populations. VEGF has also been implicated in alteration of amyloid precursor protein family processing. Our lab demonstrated that amyloid precursor protein 2 (APLP2), a member of the amyloid precursor protein family, plays an important role in the migration of tumor cells. APLP2 is known to be expressed by macrophages, but no studies have previously examined macrophage functions that are impacted by APLP2 in the context of neuroblastoma disease and its treatment by HDACi drugs.
Significance of Problem: Because of the high morbidity and mortality associated with neuroblastoma, studies such as this one that are designed to comprehend the interaction of immunity and treatment in neuroblastoma are clinically significant. The results from this study are also expected to expand our comprehension of macrophage function and regulation, and thus will be of broad value in the immunology and oncology fields.
Experimental Design and Results: We have treated neuroblastoma tumor cells in vitro with M344, an HDACi with structural similarity to vorinostat, and showed that M344 decreases neuroblastoma cell growth. In addition, we have generated mice that lack APLP2 expression in cells expressing the Csf-1 receptor (a protein characteristically expressed by macrophages and dendritic cells). We discovered that following polarization, macrophages collected from the bone marrow of these mice have an altered distribution of M1 and M2 sub-populations, which are macrophage sub-populations known to differ in their migratory capabilities. Furthermore, we have shown that M1 and M2 subpopulations of bone marrow-derived macrophages from normal mice differ in their expression of APLP2. Thus, APLP2 is influential in macrophage biology, and we have created a novel mouse model for defining its specific contributions in mice treated with HDACi that influence macrophage biology.
Conclusions: Based on the data that we have acquired, we are well positioned to fully explore both the impact of HDACi drugs on macrophage/dendritic cell populations in a syngeneic neuroblastoma mouse model, and to define the role of APLP2 in the function of these cell populations in the context of neuroblastoma.
Morgan Busboom, Anna Reelfs, Mike Trevarrow, Brad Corr, Heidi Reelfs, Sarah Baker, Hannah Bergwell, Tony W. Wilson, and Max J. Kurz
Background: Our magnetoencephalographic (MEG) brain imaging studies have shown that youth with cerebral palsy (CP) demonstrate altered sensorimotor beta (18-24Hz) cortical oscillations when controlling their leg motor actions and these anomalous cortical oscillations are linked with the extent of their mobility impairments. Current therapeutic trends for improving mobility have shifted from strength training to high-velocity power training, which has shown improvements in isokinetic strength, power production and mobility of youth with CP. However, no studies have assessed whether these clinically relevant improvements are linked with changes in the sensorimotor cortical oscillations. The objective of this study was to utilize MEG brain imaging to examine the potential changes in sensorimotor cortical oscillations following power training.
Methods: Youth with CP (N=11; Age=15.9 ±1.1yrs; GMFCS I-III) and neurotypical controls (NT) (N=16; Age=14.6 ±0.8yrs) were recruited to participate in this study. The youth with CP underwent 24 high-velocity leg press power training sessions that were performed on a Total Gym® sled. Pre-Post bilateral leg press 1-repetition maximum (1RM) and peak power production were used to assess the muscular performance changes. The 1-minute walk was used to assess mobility changes. During MEG recordings, participants used their right leg to complete a goal-directed isometric target-matching task. Advanced beamforming methods were subsequently used to image the strength of the sensorimotor beta oscillatory power. The NTs only underwent the baseline MEG assessment.
Results: Youth with CP increased their 1RM (Pre=158.3 ±24.7kg, Post=247.5 ±41.5kg, p<0.01), and peak power production (Pre=509.9 ±64.7W, Post=677.1 ±113.3W, p=0.04). Participants with CP also improved their 1-minute walk (Pre=77.4 ±9.2m, Post=80.8 ±8.4m, p = 0.02). The beta sensorimotor cortical oscillations in the leg region were stronger in the youth with CP prior to training compared with the NTs (CP=-25.9±1.8%; NT=-17.2±3.6%, p=0.04). However, the youth with CP had a reduction in the strength of the beta oscillations after undergoing the power training (pre=-25.9 ±1.8%, post=-14.8 ±3.6%, p=0.02), and the strength of the oscillations was not significantly different from the NTs after training (p=0.68). Lastly, the peak power production after training was tightly linked with the strength of the post-therapy sensorimotor cortical oscillations (r=0.79, p=0.03).
Conclusion: Power training appears to improve the neural generators that control the leg motor actions, and these neuroplastic changes partly contribute to improvements in the peak power production of youth with CP. Potentially, power training might provide the key therapeutic ingredients for complementary muscular and neurological plastic change.
I wrote this poem about my experience in the NICU taking care of babies with total anomalous pulmonary venous return (TAPVR).
I’ve been tempted to write a drum part with the heart beat as the foundation for a long time. I had the idea to tell the story of a newborn with congenital heart disease through the stages of pre-operative life, cardiac surgery, and post-op ICU care. I chose Truncus Arteriosus as the specific lesion because of the rapid neonatal course and the rich sonic landscape it provides. To “spice” things up a bit, I incorporated all sorts of physical exam findings and arrhythmias into the piece (and took a few percussive liberties to make it easier on the ears).
Aaron Clem, Lois J. Starr, David Danford, Mary Craft, Ling Li, Jason Christensen, and Anji Yetman
Marfan syndrome is caused by a mutation in the fibrillin-1 gene that manifests with a variety of features including aortic root dilation. Recent research has identified a primary cardiomyopathy in patients with Marfan syndrome, hypothesized to be due to the presence of abnormal fibrillin-1 in the myocardium. Controversy over the nature and significance of this cardiomyopathy remains. Echocardiographic measurement of the first-phase of ejection (defined as the beginning of systole to peak aortic valve flow) may be more sensitive to systolic dysfunction and provide useful clinical information. The purpose of this study is to:
- Assess systolic dysfunction in patients with Marfan syndrome
- Describe first-phase fractional area change (FAC1) in patients with Marfan syndrome and determine how it varies between Marfan syndrome patients and a control group
- Verify there is a difference in propensity for cardiomyopathy in mild vs severe gene mutation Marfan syndrome patients not secondary to increased aortic stiffness
Patients were identified from a pre-existing list of patients with Marfan syndrome maintained by the Children's Hospital and Medical Center and University of Nebraska Medical Center. All relevant medical records were reviewed. Echocardiographic parameters will include left ventricular (LV) ejection fraction, LV FAC1, LV end-diastolic volume, global longitudinal strain, aortic root diameter, and aortic stiffness. Patients were excluded if they have more than mild aortic insufficiency or mitral valve regurgitation. Neonatal Marfan syndrome patients and patients with other significant congenital heart disease will also be excluded. Statistical analysis of the data will be performed including basic statistical tests, univariate regression, and multivariate regression to compare data from each group. P values will be calculated and a p value < 0.05 will be considered statistically significant.
At the time of writing, 126 patients with Marfan syndrome have been identified. 44 were excluded based on significant mitral or aortic valve disease, prior cardiovascular surgery, or poor echocardiographic image quality. Of the 82 patients not excluded, genetic testing results are available for 59 and are being categorized to allow for statistical analysis. Echocardiographic measurements are underway.
Amanda Dave, Luke Allen, Zeljka Korade, and Eric Peeples
Neonatal hypoxic-ischemic brain injury (HIBI), resulting from impaired cerebral blood flow and oxygen delivery to the brain, affects at least 1.5 per 1,000 live births each year in the United States. Altered levels of cholesterol and cholesterol metabolites have been identified in brain tissue and in serum after adult brain injury such as traumatic brain injury and stroke. We hypothesized that there would be temporal and brain region-specific alterations in cholesterol and sterol precursors after neonatal HIBI.
Postnatal day 9 CD1 mouse pups were anesthetized with isoflurane and randomized to HIBI induced by carotid artery ligation or controls receiving sham surgery consisting of dissection without ligation (n=24/group). Pups were allowed to recover after surgery and then placed in a hypoxia chamber at 8% oxygen for HIBI or 21% for controls for 30 minutes. Each group was further divided into three sub-groups (n=8/group) for blood and brain tissue collection at 30 minutes, 24 hours, or 72 hours after injury. Brain tissue was dissected into four regions: cortex, cerebellum, striatum/thalamus, and hippocampus. For each region, protein was quantified by BCA assay, interleukin-6 (IL-6) levels were measured by ELISA as a marker of injury severity, and liquid chromatography mass spectrometry was performed to evaluate for the following sterols: cholesterol, desmosterol, 7-dehydrocholesterol, 8-dehydrocholesterol, and lanosterol. Levels were compared between HIBI and control groups at each time point and neuroanatomical region. Additionally, the four samples in each group demonstrating the most severe injury, as defined by IL-6 levels, were stratified as “severe injury”. Differences were analyzed with a two-sided Mann-Whitney test.
When assessing the entire cohort, no statistically significant differences were seen between HIBI and controls with respect to temporal or regional differences for any of the sterols measured. In animals with severe HIBI, however, cholesterol, 7-dehydrocholesterol, 8-dehydrocholesterol, and desmosterol were higher in the cortex at 24 hours after injury compared to controls. Additionally, desmosterol was also elevated in the cerebellum but decreased in the striatum 24 hours after injury in the severely injured animals.
Severe neonatal encephalopathy appears to be associated with alterations in cortical brain sterol levels, peaking around 24 hours after injury. Further defining the aberrations in brain metabolism in infants with HIBI could provide opportunities for not only diagnostic biomarkers but also the development of targeted therapies.
Femoral and Tibial Indications for Initial and Reoperation Surgeries with Fassier-Duval Intramedullary Rods for Children with Osteogenesis Imperfecta
Adriano DellaPolla, Kaeli Samson, Tinotenda Sekeramayi, Arianna Dalamaggas, Megan Gillespie, Vincent Eaton, Elizabeth Strudthoff, and Maegen Wallace
Background: Osteogenesis imperfecta (OI) is a genetic connective tissue disorder affecting quantity and integrity of collagen type I, which is integral for the strength of osseus tissue. OI has a heterogenous molecular inheritance pattern – divided into four major subgroups (I-IV). Defects in collagen protein products lead to poor development of skeletal structures and increased fracture rates. Children with OI suffer from multiple fractures and bone deformities often requiring surgical intervention with osteotomies and intramedullary telescoping rods, most often with Fassier-Duval (FD) rods. Our study–updated cohort from 2018 paper Azzam et al.–looked at the relationship between initial and reoperation indications for femur and tibia FD rodding surgeries based on age, bone, and OI type.
Methods: Retrospective chart review of initial surgeries included 197 bones (femurs and tibias) from 58 patients. Reoperations included 140 bones from 45 patients. Variables included age at first operation (0-24, 24.1-48, 48.1+ months), time to reoperation, operation indications, bone, and OI type. Spearman correlations were used separately for each bone-type to assess associations between age at first surgery and total number of surgeries. To assess dichotomous outcomes (i.e. specific indication), generalized estimating equations were utilized and adjusted for bone-type and side. Hazard ratios and associated 95% confidence intervals were derived from frailty survival models for the time to first reoperation outcome. Kaplan-Meier curves were generated to display time to reoperation, stratified by age at first operation and bone-type. Data was collected from 2003-2018. Analyses were performed using SAS software v9.4.
Results: There was a statistically significant correlation between age at first surgery and indication (bowing and fracture) for initial (p<0.0001, p=0.01) and reoperation surgeries (p=0.004, p=0.03), respectively. All bones, except left tibias, showed significant negative correlation between age at first surgery and total number of surgeries. Both older age at first surgery groups (24.1-48, 48.1+ months) had significantly lower risks of needing reoperation relative to the 0-24 months group (p=0.0003, p=0.0004). Descriptive analyses suggest median survival of FD rods in OI type III was decreased relative to type IV, XV or unknown when initial surgery was between 0-24 months.
Conclusion: Bowing and fractures are the most common causes for initial and reoperation surgeries in children with OI. Patients in older age groups at first surgery need fewer reoperation surgeries. Median survival probabilities of FD rods increased when age at first surgery was after 48.1+ months. OI type may impact median survival of FD rods.
Evaluation of Pseudomonas aeruginosa Eradication Protocol in Pediatric Patients with Cystic Fibrosis: A Retrospective Medical Chart Review
Adam DeVries, Heather Thomas, and Diane Acquazzino
Pseudomonas aeruginosa (Pa) is a leading cause of lung infection in patients with cystic fibrosis (CF), increasing morbidity and mortality. Despite this, there is no standardized treatment among the medical community for Pa eradication in patients with CF. The Nebraska Regional Cystic Fibrosis Center at Children’s Hospital and Medical Center (CHMC) in Omaha, Nebraska has a Pa eradication protocol. This study aims to increase Pa eradication for children with CF by investigating the effectiveness and adherence to the current Pa eradication protocol.
This study is a retrospective medical chart review of 1–21-year-olds with CF receiving care at CHMC. Medical records for each patient were screened for Pa culture results and Pa treatments. Primary endpoints were the degree of protocol adherence, eradication success, and subsequent colonization following CHMC’s Pa eradication protocol. The current protocol starts patients on step one with inhaled tobramycin for 28 days and oral ciprofloxacin for 14 days following a positive Pa culture. If still positive after that time, they are started on step two with 10-14 days of intravenous antibiotics. If sustained positivity following IV antibiotics, they progress to step three with six months of alternating monthly inhaled tobramycin, colistin, or aztreonam. If positivity after step three, they are considered colonized. If they have a negative sputum culture following any step, Pa is considered eradicated, they continue quarterly monitoring, and restart the protocol following another positive Pa result.
Of the 184 CHMC’s CF patients, 172 patients were used for the study (8 excluded for age and 4 for inadequate medical records). For those included, the protocol was fully followed correctly for 70.3% (N=121) of patients. When step one of the protocol was followed, 151/206 (73.3%) of treatments had Pa eradication compared to 36/61 (59.0%) of patients with non-protocol treatment (OR 0.52, 95% CI 0.29-0.95, P=0.03). However, there was no statistically significant difference in eradication when comparing steps two and three to non-protocol treatments. When the complete protocol was followed, 12/121 (9.9%) of patients became chronically colonized with Pa compared to 27/51 (52.9%) of patients who did not follow protocol guidelines (OR 0.099, 95% CI 0.04-0.22, P-value= <0.0001).
Adherence to the CHMC’s current protocol is associated with increased Pa eradication levels when used at step one and decreased colonization cases. Early initiation of treatment using this protocol is vital to improving morbidity and mortality associated with Pa infections in cystic fibrosis children.
Pencil drawing and embroidery. The piece is representing the physiological changes happening daily in our brains. Health care is a field where learning happens daily, which is especially evident as a medical student.
December 18th, 2020 Memorial Park Omaha, Nebraska. This picture was taken December 18th in Memorial Park. I treated myself to a delightful walk that evening after finishing my neurology shelf and first semester of M3 year.
A reflection of the stress and wonder surrounding M3 year
Emilee Greager, Mary Conklin, Jordan Nustad, Tyler Bendrick, Haley Bremer, Tavishi Chopra, Jane Driano, Connor Eggleston, Lily Foley, Jeffrey Kepple, Ryan Leuty, Taylor Mattice, Alison Mause, Elizabeth Mause, Molly Olsen, Breanne Parets, Heerali Patel, Thomas Pennington, Miranda Prints, Eva Schaible, Christopher Toivonen, Grace Vitek, Claire Willman, Allen Zheng, and Kody Moffatt
Background: The prevalence of childhood obesity is increasing across the country. Health education at a young age is critical for children to establish healthy habits. The Fit for Life program is put together by Creighton medical students to inspire elementary students to lead a healthy lifestyle. The curriculum integrates physical exercise, real organ demonstrations, emotional wellness exercises, and nutritious meal building to model and encourage healthy habits.
Methods: Over four weeks, medical students taught the 4th and 5th graders of two Omaha schools over live video while they followed along with hands-on activities. Before and after the program, students’ height and weight were measured to calculate BMI, and the students completed pre- and post-program quizzes. Paired t-tests were performed to analyze differences in student BMIs and quiz scores. Pre-program quiz scores of students who completed two consecutive years were compared using paired t-tests.
Results: Student BMIs before and after the program showed no significant changes (p = 0.479, n = 45) however, quiz scores significantly improved after the program (p < 0.001, n = 44). Self-reported survey responses after the program demonstrate increased motivation for a healthy lifestyle as well as improved understanding of the importance of sleep, exercise, reduced screen time, and healthy eating. Those who completed the program for two consecutive years had significantly higher pre-program quiz scores the second year (p < 0.05, n = 18).
Conclusion: Our study found a significant increase in pre- and post-program assessment scores which suggest improvement in student perspective and knowledge of healthy habits. Similarly, students who completed the program for two consecutive years demonstrated an increase in pre-program quiz scores suggesting retention of health knowledge. While there was no significant difference in pre- and post-program BMIs, results may be limited by the duration of the study, given that changes in weight are often insubstantial in the short-term.
Do I add value? A mixed methods study comparing medical students’ experiences with patient documentation
Shannon Haines, Kari Nelson, Kaeli Samson, and Nathan Gollehon
Clinical documentation is an essential skill for practicing physicians, yet many medical students are not prepared for the documentation demands required during residency.1,2 Recent CMS rule changes now allow medical students’ notes to be used for billing.3 Previous studies have shown positive perceptions of medical students whose notes were used in an outpatient setting.4 We utilized Constructivist Learning Theory to frame our work, where students construct their knowledge as faculty and residents facilitate the process.5
To explore if using student documentation for billing impacts student perceptions and experiences during the pediatric clerkship.
Pediatric clerkship students were randomly assigned to one of two inpatient hospitalist teams: Control group students (n=28), whose daily notes were not addended or used for billing purposes, and Study group students (n=42) who wrote notes that were used for billing. After study group students signed the notes, they were addended and cosigned by a resident and subsequently a faculty member who submitted the note for billing. There was no specific feedback structure or documentation curriculum provided to either study arm. We utilized a sequential mixed methods approach (quant+qual), with a survey that included fixed response and open-ended questions, as well as an opportunity to participate in a focus group. Differences in Likert-type questions between groups were assessed with Wilcoxon Rank Sum tests. Open-ended survey responses and focus groups were analyzed using inductive thematic analysis, with consensus among 3 researchers and respondent validation.
Study group students found their experience more valuable, rated the usefulness of feedback from residents higher, and spent more time reviewing edits to their notes than their peers in the control group (p=<0.05).In focus groups and open-ended survey responses, themes from the study group included feeling more useful to the team and receiving more one-on-one feedback. They also reported that there was feedback inherent in reviewing supervisors’ edits to their notes. Control group students reported they focused their time on tasks other than note writing. Both groups reported that the practice of writing notes helped organize their thoughts and plans.
In this exploratory study, use of student notes for billing was associated with feelings of value and enhanced feedback compared to students whose notes were not used. These findings support the use of medical student notes for documentation as a worthwhile educational practice and highlight the need for further study to define curricular interventions that foster development of this essential professional skill.
To addend or not to addend? Exploring pediatric residents' perceptions of using medical students’ notes for documentation, a mixed methods approach
Shannon Haines, Kari Nelson, Kaeli Samson, and Nathan Gollehon
Clinical documentation is an essential skill for practicing physicians, yet many medical students are not prepared for documentation required during residency.1,2 CMS rule changes now allow medical students’ notes to be used for billing.3 Residents are often the primary authors of notes and provide medical student supervision and instruction. However, little is known about how the use of medical student notes in patient documentation would impact residents. We utilized Constructivist Learning Theory to frame our work, where students construct their knowledge as residents and subsequently faculty facilitate the process.4
To evaluate how utilizing clerkship medical student notes for billing in the inpatient setting impacts resident learners.
Pediatric clerkship students were randomly assigned to one of two inpatient hospitalist teams: Control group students wrote daily notes that were not addended or used for billing purposes; and Study group students wrote notes that were used for billing. After study group students signed the notes, they were addended and cosigned by a resident and a faculty member who submitted the note for billing. There was no structured feedback or documentation curriculum provided to either study arm. We utilized a sequential mixed methods approach (quant + QUAL); junior and senior residents were given a survey with Likert-type items related to their satisfaction with the process, and an opportunity to participate in focus groups. Sixteen residents who supervised the control group and twenty residents who supervised the study group completed the survey, with responses analyzed using Wilcoxon Rank Sums tests. Focus groups were analyzed using inductive thematic analysis, with consensus among three researchers and respondent validation of participants.
In surveys, residents supervising both groups reported similar satisfaction scores with medical student documentation. There was a trend towards increased time spent providing feedback on notes among the study group, but this did not reach statistical significance. In focus groups, emergent themes included the educational value for students and residents, positive impacts on student experience, minimal negative impacts on patient care, and possible impacts on team workflow.
Medical students' notes are being increasingly used for EMR/billing; therefore, it is important to understand upstream effects on other learners. Recently published qualitative research has explored the resident perspective, but did not use a control group, and had varying results from our own with regard to workflow.5 If use of student notes for billing is to become common practice, more study is needed to understand the impacts on resident learners.
1. Englander R, et al(2016) Toward defining the foundation of the MD degree: Core entrustable professional activities for entering residency. Academic Medicine. 91(10):1352-1358.
2. Power D, Byerley J, Steiner B. (2018) Policy change from the centers for Medicare and Medicaid Services provides an opportunity to improve medical student education and recruit community preceptors. Academic Medicine,
3. Department of Health & Human Services. CMS Manual System Publication100-04 Medicare claims processing:
4. Bruner, J.S. (1961). The act of discovery. Harvard Educational Review, 31: 21-32.
5. Safdar K, Dombrosky EM, Kimberly C, et al. The One Note System: Implementation and Initial Perceptions of Student Documentation in the Electronic Health Records Under the New Centers for Medicare and Medicaid Services Guidelines. Cureus. 2020;12(8):e9702. Published 2020 Aug 12. doi:10.7759/cureus.9702
Shannon Hegemann and Chinenye Dike
Development of splanchnic venous thromboses is a known consequence of pancreatitis, most commonly of the splenic vein. As development of venous thromboses is an uncommon complication of acute recurrent pancreatitis or chronic pancreatitis, there is limited evidence for detection and management. This pediatric recurrent pancreatitis case series demonstrates detection of splenic vein thromboses with subsequent treatment with therapeutic injectable anticoagulation, and then transition to oral anticoagulation with resolution of the thromboses at follow up.
A 13-year-old female with obesity (BMI 99th percentile) and a family history of hereditary pancreatitis presented with her second episode of acute pancreatitis and was started on prophylactic enoxaparin upon admission. On hospital day 6, an abdominal CT showed development of a nonocclusive splenic vein thrombosis and the enoxaparin was increased to therapeutic doses. The patient’s anticoagulation was changed to oral rivaroxaban prior to discharge, which she maintained for several weeks. Follow up ultrasound three months after discharge demonstrated resolution of the splenic vein thrombosis.
A 9-year-old female with obesity (BMI 99th percentile) presented with her third episode of acute pancreatitis requiring IV fluids and opioids for pain management. On hospital day 3, an abdominal CT showed significant worsening of necrotizing pancreatitis involving the entire pancreas and an occlusive splenic vein thrombosis. She was subsequently initiated on therapeutic enoxaparin. Due to severe needle phobia during hospitalization demonstrated while receiving her twice daily enoxaparin injections, she was switched to oral rivaroxaban at discharge. A follow up CT scan five months later revealed near complete resolution of the extensive splenic thrombosis.
Direct oral anticoagulants (DOACs) should be considered in pediatric patients with pancreatitis-induced thrombosis (PIT) over low-molecular-weight heparin as they have been shown to be as efficacious and safe in the treatment of thromboses in other clinical conditions and are more likely to be more acceptable to the pediatric patient with pancreatitis. Furthermore, the use of DOACs in PIT is an area in critical need for research.
Margaret Hogan Smoot and Terrance Zach
A female infant was born by cesarean section at 36 weeks of gestation after the mother presented with perceived decreased fetal movement, blood-tinged mucous vaginal discharge, and a non-reactive non-stress test. Upon delivery, the infant appeared extremely pale and in mild respiratory distress. A complete blood count upon admission showed profound neonatal anemia, and a Kleihaur-Betke test confirmed fetomaternal hemorrhage as the cause. Transfusions corrected the infant’s hematocrit levels, and she was discharged on day 8 following a normal brain MRI. Fetal to maternal hemorrhage is a known cause of neonatal anemia, however the presentation is nonspecific leading to underdiagnosis which can cause serious complications including infant death. Fetomaternal hemorrhage is a rare and severe phenomenon which requires increased awareness, improved diagnostic testing, and further research.
Ranjana K. Kanchan, Naveenkumar Perumal, Pranita Atri, Ramakanth C. Venkata, Ishwor Thapa, Mohd W. Nasser, Surinder K. Batra, and Sidharth Mahapatra
Introduction Among CNS tumors, medulloblastoma (MB) is the most common malignant pediatric brain tumor. Of the four subgroups, group 3 (G3MB) tumors fare the worst. Haploinsufficiency of 17p13.3 is a hallmark of these high-risk tumors; included within this locus is miR-1253, which has tumor suppressive properties in medulloblastoma. Therapeutic strategies capitalizing on the anti-neoplastic properties of miRNAs can provide promising adjuncts that can improve efficacy while mitigating toxicity of current chemotherapeutic drugs.
Objective In this study, we explored the potentiation of miR-1253 on cisplatin cytotoxicity in group 3 MB.
Methods We used RNA Sequencing to isolate a putative target for miR-1253 that is upregulated in G3MB, has a poor prognostic profile, and is involved in iron balance/ferroptosis. Calein AM quenching, COX IV staining and multiple stains for iron were used to study mitochondrial vs. free cytosolic iron generation. Confocal microscopy and FACs analyses were used to examine ROS generation and lipid peroxidation. Using 2 classical group 3 MB cell lines, possessing c-Myc amplification and i17q, we determined the IC50 of cisplatin in the presence of miR-1253 expression using MTT assay. We also studied colony formation, apoptosis and oxidative stress, as cisplatin is an inducer of both. Finally, ROS and ferroptosis inhibitors were used to study effects on tumor cell rescue from miR-1253 and cisplatin therapy.
Results In silico and in vitro analyses revealed upregulation of ABCB7 in G3MB cancer cells and tumors. Overexpressing miR-1253, in turn, suppressed ABCB7, revealing it as a putative target with poor survival in high-expressing MB tumors. Overexpression also led to a suppression of GPX4, a ferroptosis regulator, consequently increasing labile iron pool within the mitochondria and resulting in mtROS induction. Cisplatin is reported as an inducer of both apoptosis and ferroptosis-mediated cancer cell death. In miR-1253-overexpressing cancer cells, we observed a cumulative effect on cell death and colony formation with cisplatin; treatment with ROS and ferroptosis inhibitors abrogated these effects.
Conclusions We conclude that miR-1253 potentiates the ferroptotic effects of cisplatin via targeting miR-1253/ABCB7/GPX4 axis.
Jeffrey Kepple and Eric Peeples
Background: Survival in trisomy 13 (T13) and 18 (T18) has increased in recent years, but little is known about the prevalence and management of the non-lethal complications in these populations.
Significance of Problem: A subjectively high rate of direct hyperbilirubinemia (DH) was noted at Children’s Hospital & Medical Center compared to the general population. Defining the prevalence, timing, and risk factors for DH will allow for the development of screening and management guidelines.
Hypothesis, Problem or Question: We hypothesized that infants with T13 and T18 would have high rates of DH, with no significant difference in prevalence between the two populations.
Experimental Design: Retrospective cohort study of infants born between Jan 1, 2012 and March 1, 2020 and admitted to the NICU at Children’s or the Nebraska Medical Center within the first month of life. Data collected included bilirubin, ALT, AST, and GGT levels, liver imaging, and any treatment administered. DH is defined as conjugated bilirubin >1 mg/dL, but the cutoff of >2 mg/dL has a higher association with underlying pathology. Fisher’s exact test and Mann-Whitney U test were used for categorical and continuous variables in DH for both cutoffs.
Results/Data: Thirty-five patients met inclusion criteria: 13 with T13 and 22 with T18. When using the >1 mg/dL cutoff, DH was seen in 7/13 (53.8%) patients with T13 and 9/22 (40.9%) with T18, which was not significantly different between the two diagnoses. Twelve of the 16 infants with DH developed DH in the first two weeks of life and, although it did not reach significance, patients with T13 tended to present with DH earlier than those with T18 (median 5 vs. 12 days of life). DH occurred more often in infants who received TPN (81.3 vs. 36.8%, p=0.016). DH was associated with higher peak AST (p=0.004), ALT (p=0.002), but not GGT (p=0.176) levels. The presence of an abnormal ultrasound was not associated with DH. Six infants were treated with phenobarbital or ursodiol, and 5/6 normalized their conjugated bilirubin levels within one week of starting therapy.
Conclusions: DH was common in infants with T13 and T18, and at a qualitatively higher prevalence than what has previously been reported in the general population, even if excluding those infants who received TPN. Clinicians should consider screening for DH starting within the first week of life in both trisomy 13 and 18, continuing weekly if <1 mg>/dL until discharge from hospital.
Karl Khandalavala, Kari Simonsen, and Jeffrey A. Robinson
Introduction: The novel SARs-CoV2 coronavirus has infected approximately 30,000,000 people in the USA. To date, approximately 146 million doses of SARs-CoV2 vaccines have been administered. Perceptions of rapid vaccine development have resulted in reported vaccine hesitancy and refusal. Though not currently FDA approved for use in pediatric populations, but pediatric vaccination may contribute to herd immunity. Previous study demonstrates that physician recommendations significantly impact perceptions of routine pediatric immunizations among parents. Given this historical data, this study aimed to describe the strength of recommendation by pediatricians for the SARs-CoV2 vaccine for pediatric patients and their parents.
Methods: A 10-question single-institution anonymous survey was distributed to physicians in the Department of Pediatrics, consisting of 2 demographic questions, 5 Likert-style survey questions on vaccine recommendations, and 2 free-responses for comments on current vaccine development for thematic analysis.
Results: There were 90 survey responses, and no responses were excluded from analysis. The most common sources of vaccine information among pediatricians were peer-reviewed journals (51%) and major broadcast or print materials (30%). A majority of pediatricians indicated that they read about vaccine information either weekly (44%) or monthly (27%). Of the survey respondents, 99% indicated that they had personally received a SARs-CoV2 vaccine. For pediatric vaccine recommendations, 69% responded that they strongly encouraged their pediatric patients to receive a SARs-CoV2 vaccine, compared to 87% recommending SARs-CoV2 vaccine for parents and 96% recommending the annual influenza vaccine. Thematic analysis of free response questions demonstrated that physicians cited the need for herd immunity (42%) and the protection of their patients (41%) as reasons for recommending the vaccine, and cited lack of research or FDA approval of vaccine use in pediatric populations (61%) as reasons for recommending against receiving the vaccine.
Conclusions: This single-center survey study demonstrated that a majority of pediatricians strongly encourage their pediatric patients to receive a SARs-CoV2 vaccine, though not as strongly as they recommend vaccination to their patients’ parents or vaccination against influenza. Thematic analysis indicated that physicians cite the need for population-level herd immunity as well as individual-level protection from SARs-CoV2 infection as a basis for their vaccine recommendations.
Rachel Nelson and Russell Hopp
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food disease characterized by delayed vomiting and diarrhea, often at the first ingestion of the food. The clinical phenotype of FPIES, including trigger food and disease course, varies by region. A literature review of the most common FPIES foods in children in the United States and worldwide includes cow’s milk, soy, oats, rice, and egg.
We sought to survey the most common FPIES foods seen at Children’s hospital in the past five years.
A data search of the EPIC electronic medical record using FPIES codes ICD-10 (K52.21) and ICD-9 (558.3) as the primary diagnosis revealed 40 cases and 23 foods.
The five most common foods seen in FPIES cases presenting at Children’s Hospital are oat, rice, sweet potato, milk and egg. Fish was much more common in our cohort than in the previously studied populations.
We also report the most recently diagnosed FPIES cases at Children’s hospital. One case with two less common food triggers, and a case of FPIES with concomitant IgE positivity to the food (atypical FPIES).
This original piece, "Spring" using chalk pastel on textured paper evokes a sense of warmth, life and playfulness. The art-work (13"x11") depicting an infant playing with a stethoscope makes use of vibrant strokes and a color scheme that I believe captures some of the more endearing features of children, a certain courage and curiosity frequently encountered by professionals within pediatrics. The infant stares back, briefly yet frozen in time, offering its attention as a gift to the viewer.
3D Printed Adjustable Glasses: A New Model of Corrective Lens Delivery for Pediatric Refractive Error in Underserved Communities
Nathan Ostlie, Mari Ogino, Donny Suh, Gabe Linke, and James Hermsen
Uncorrected refractive error (URE) remains a major cause of preventable vision impairment in the pediatric population with large inequities in disease burden. The present study aims to elucidate the global burden of pediatric URE and explore the current lens delivery systems which address this problem. Within this framework, we introduce a new model of corrective lens delivery that may improve upon existing models.
The present study involved an extensive literature review of epidemiological data to determine the global prevalence of URE. Prevalence data was then compared against WHO data on refractionist coverage gaps divided by region. Four current models for corrective lens delivery, plus our newly proposed model, were compared across five general categories (Fit, Appearance, Pathologies Corrected, Cost to Patient, Distribution System).
In children, the estimated pooled prevalence (EPP) of myopia, hyperopia, and astigmatism was 11.7% (95% CI: 10.5–13.0), 4.6% (95% CI: 3.9–5.2), and 14.9% (95% CI: 12.7–17.1), respectively. The highest prevalence of astigmatism and hyperopia occurs in The Americas at double and triple the global average respectively. The regions with the poorest coverage of URE were Sub-Saharan Africa, Southeast Asia and The Americas. Existing solutions delivering coverage to these areas often lacks the ability to correct for astigmatism. Our modular glasses design provides a one-size-fits-all frame with circular lens mounts to accommodate any axis of astigmatism. 3D printed materials allow these frames to be constructed at a fraction of the cost of conventional frames.
While corrective lenses are made available through a variety of distribution models, the infrastructure to fit and deliver these glasses to remote and resource poor areas remains a major challenge leading to inequities in URE treatment. The flexibility of our glasses design allows for these glasses to be distributed in rural and urban environments alike, with minimal training required to fit and assemble, at a low cost to patients.
Encephalocele is a defect of the neural tube. Dandy Walker malformation (DWM) is a defect involving agenesis or hypoplasia of the cerebellar vermis, cystic dilation of the fourth ventricle, and enlargement of the posterior fossa. This is a case of a female preterm infant born at 36 weeks’ gestation who presented with DWM and an encapsulated occipital encephalocele at birth. The pregnancy was complicated by poorly controlled maternal diabetes. Prenatal ultrasound indicated a central nervous system anomaly. Amniocentesis did not show chromosomal abnormality. The infant also presented with polydactyly of the right thumb. MRI showed evidence of soft tissue within the defect and confirmed the presence of DWM. Renal ultrasound was normal. Whole exome sequencing revealed three variants of possible pathologic or unknown significance. No variants of known clinical significance were found. The encephalocele was repaired by ventriculoperitoneal shunt and cranioplasty at 18 days of age.
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