Utility of illness symptoms for predicting COVID-19 infections in children.

BACKGROUND: The Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend that symptomatic children remain home and get tested to identify potential coronavirus disease 2019 (COVID-19) cases. As the pandemic moves into a new phase, approaches to differentiate symptoms of COVID-19 versus other childhood infections can inform exclusion policies and potentially prevent future unnecessary missed school days. METHODS: Retrospective analysis of standardized symptom and exposure screens in symptomatic children 0-18 years tested for SARS-CoV-2 at three outpatient sites April to November 2020. Likelihood ratios (LR), number needed to screen to identify one COVID-19 case, and estimated missed school days were calculated. RESULTS: Of children studied (N = 2,167), 88.9% tested negative. Self-reported exposure to COVID-19 was the only factor that statistically significantly increased the likelihood of a positive test for all ages (Positive LR, 5-18 year olds: 5.26, 95% confidence interval (CI): 4.37-6.33; 0-4 year olds: 5.87, 95% CI: 4.67-7.38). Across ages 0-18, nasal congestion/rhinorrhea, sore throat, abdominal pain, and nausea/vomiting/diarrhea were commonly reported, and were either not associated or had decreased association with testing positive for COVID-19. The number of school days missed to identify one case of COVID-19 ranged from 19 to 48 across those common symptoms. CONCLUSIONS: We present an approach for identifying symptoms that are non-specific to COVID-19, for which exclusion would likely lead to limited impact on school safety but contribute to school-days missed. As variants and symptoms evolve, students and schools could benefit from reconsideration of exclusion and testing policies for non-specific symptoms, while maintaining testing for those who were exposed.

Medications Without Borders: Themes in Caregiver Administration of Imported Medications in Pediatrics.

OBJECTIVE: This study aimed to identify motivating factors in why parents administer imported medications to their children. METHODS: In this qualitative study, we enrolled caregivers of patients younger than 18 years who presented for care at a pediatric emergency department. The study team conducted face-to-face interviews with caregivers in the emergency department and used a semistructured question guide to probe for themes regarding the use of imported medications in children. Interviews were recorded, transcribed, translated if necessary, and coded. We applied grounded theory methodology to assess for themes and adapted the Andersen model of health care utilization to provide a framework for the identified themes. RESULTS: We completed 30 interviews, 9 of which were conducted in Spanish. Themes surrounding imported medication usage were categorized into predisposing, enabling, and need factors. Predisposing factors included perception that an ill child needs medication to get better, perception of medication quality, and past experiences with medications. Enabling factors included proximity to foreign countries, cost, limited access to primary care, and convenience of obtaining medications. Need factors included utilization of foreign medications for a "simple illness" and utilization of foreign care for a "second opinion." CONCLUSIONS: Our study used qualitative methodology to gain important insights into the caregiver experience of a diverse patient population. We identify themes not previously published in the medication importation literature. These concepts can provide insights in educational strategies aimed at mitigating the potential dangers of imported medication use in pediatrics.

Seated Position Does Not Change Lumbar Dimensions Compared With Lateral Position.

OBJECTIVE: The infant lumbar puncture (LP) can be a technically challenging procedure. Understanding the anatomical lumbar dimensions may optimize LP conditions. Data from preterm neonates, older children, and adults indicate measurements of the lumbar spine in the seated LP position may be superior when compared with the lateral position. We use point-of-care ultrasound (US) to determine if the seated position, when compared with the lateral decubitus position, significantly affected the lumbar dimensions of infants 12 months or younger presenting to the pediatric emergency department. METHODS: We conducted a prospective observational study of a convenience sample of patients 12 months or younger. We used US to obtain 3 still images oriented longitudinally in the midline over the L3 to L4 interspace in the lateral decubitus and seated positions. A US fellowship-trained emergency physician, blinded to patient position, measured interspinous space, subarachnoid space width, and spinal canal depth. We then compared the means of all 3 dimensions in the lateral and seated positions. RESULTS: From 50 subjects, 49 subjects provided 46 evaluable sets of images for each measure. Interspinous space, spinal canal depth, and subarachnoid space width did not differ significantly between positions. Mean differences did not exceed 0.02 cm for any of the measured dimensions. We report no significant differences in the 3 lumbar dimensions at the seated position when compared with the lateral decubitus position. CONCLUSIONS: For infants younger than 12 months, sonographic measurements of lumbar dimensions did not differ between the positions commonly used for LP.

Cigarette smoke extract induces oral squamous cell carcinoma cell invasion in a receptor for advanced glycation end-products-dependent manner.

Oral squamous cell carcinoma (OSCC) affects approximately 30,000 people and is associated with tobacco use. Little is known about the mechanistic effects of second-hand smoke in the development of OSSC. The receptor for advanced glycation end-products (RAGE) is a surface receptor that is upregulated by second-hand smoke and inhibited by semi-synthetic glycosaminoglycan ethers (SAGEs). Our objective was to determine the role of RAGE during cigarette smoke extract-induced cellular responses and to use SAGEs as a modulating factor of Ca9-22 OSCC cell invasion. Ca9-22 cells were cultured in the presence or absence of cigarette smoke extract and SAGEs. Cell invasion was determined and cells were lysed for western blot analysis. Ras and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) activation were determined. Treatment of cells with cigarette smoke extract resulted in: (i) increased invasion of OSCC; (ii) increased RAGE expression; (iii) inhibition of cigarette smoke extract-induced OSCC cell invasion by SAGEs; (iv) increased Ras, increased AKT and NF-κB activation, and downregulation by SAGEs; and (v) increased expression of matrix metalloproteinases (MMPs) 2, 9, and 14, and downregulation by SAGEs. We conclude that cigarette smoke extract increases invasion of OSCC cells in a RAGE-dependent manner. Inhibition of RAGE decreases the levels of its signaling molecules, which results in blocking the cigarette smoke extract-induced invasion.

Emergency Department Point-of-Care Hip Ultrasound and Its Role in the Diagnosis of Septic Hip Arthritis: A Case Report.

We present a case of an 11-year-old girl with eye swelling and hip pain and the use of point-of-care hip ultrasound (US) to facilitate diagnosis of a septic hip. We review the US technique, sonographic findings, and relevant literature regarding point-of-care hip US.

Identification of orally-bioavailable antagonists of the TRPV4 ion-channel.

Antagonists of the TRPV4 receptor were identified using a focused screen, followed by a limited optimization program. The leading compounds obtained from this exercise, RN-1665 23 and RN-9893 26, showed moderate oral bioavailability when dosed to rats. The lead molecule, RN-9893 26, inhibited human, rat and murine variants of TRPV4, and showed excellent selectivity over related TRP receptors, such as TRPV1, TRPV3 and TRPM8. The overall profile for RN-9893 may permit its use as a proof-of-concept probe for in vivo applications.

Pediatric Cranial Vault Fractures: Analysis of Demographics, Injury Patterns, and Factors Predictive of Mortality.

BACKGROUND: Pediatric cranial vault fractures are a unique subset of injuries that pose distinct management and treatment challenges. They are anatomically distinct from their adult counterparts with potential implications on the development of the brain and craniofacial skeleton, and require unique considerations for management and treatment outcomes.A detailed analysis of the characteristics and outcomes of pediatric cranial vault fractures remains understudied in this population. Thus, the aim of this study was to characterize the demographics, injury patterns, operative interventions, concomitant injuries, and factors predictive of mortality in pediatric patients sustaining cranial vault fractures. METHODS: A retrospective review of patients less than 18 years of age presenting to the emergency department of a pediatric level I trauma center between 2000 and 2005 with skull fractures was performed. All patients were included regardless of treating specialty, treatment modality, or inpatient status. Patients were stratified into 3 groups (age < = 5 yrs, 5.1-11 yrs, and >11 yrs). ZIP codes were mapped using ArcGIS 10.2 Software (ESRI Inc, Redlands, CA) with ZIP code shapefiles from ESRI's ArcGIS Online. Socioeconomic and demographic variables at the ZIP code level were linked to each geocoded location using the United States Census Bureau summary files, and spatial clusters of injury were performed using GeoDa to conduct a test of local indicator of spatial autocorrelation. Statistical analysis was performed using the SPSS version 17 (SPSS Inc, Chicago, IL). RESULTS: A total of 923 consecutive patients met the inclusion criteria for the study. Caucasian (P < 0.001) males (P = 0.055) were most likely to sustain cranial vault fractures. The average age at injury was 5.97 years. Falls (53.7%) were the most common cause of injury across all age groups, followed by collisions (20.8%), with falls being more common in the youngest age group (< = 5 yrs), and collisions being more common in the older age groups. Direct objects to the head had the highest rate of surgical intervention (P < 0.001). Parietal bone fractures were more frequent in the youngest age group, while frontal and temporal bone fractures were more common in the older age groups. Increasing age was an independent predictor of the need for surgical intervention (P < 0.0001). The overall incidence of blindness and hearing loss was low, and increased with increasing age. Patients with fractures as a result of violent mechanisms were more likely to come from highly impoverished zip codes, compared with patients with nonviolent mechanisms of injury (19.6% versus 8%). Overall mortality was low (2.9%). Temporal bone fractures had the greatest risk of mortality (P < 0.001) with age > = 5 years being an independent predictor of mortality (P < 0.001). Victims of falls, and patients with associated gastrointestinal or musculoskeletal injuries, had a statistically significant increased chance of survival, whereas victims of collisions and patients with concomitant cervical spine, cardiothoracic, or respiratory injuries had a significantly increased risk of death. CONCLUSIONS: Pediatric cranial vault fracture injury patterns are significantly correlated with demographics, mechanisms of injury, presence and type of concomitant injuries, need for surgical intervention, and mortality. Although the need for operative intervention and overall mortality is low, these variables play significant roles in portending prognosis, and an understanding of the metrics presented herein will enable practitioners optimize management and treatment in this unique patient population.

Geographic Patterns of Youth Suicide in San Diego County.

OBJECTIVE: Our objectives were to evaluate for any cluster patterns of youth suicide deaths and characterize the level of child opportunity in the communities where suicide deaths occurred. METHODS: Decedents <18 years were identified from San Diego County Medical Examiner death reports from 2000 to 2020. We mapped decedents' residential Zone Improvement Plan (ZIP) codes and calculated suicide rates per 10,000 youths. ZIP codes identified in overlapping spatial statistical approaches - the spatial scan statistic and Local Moran with Empirical Bayes (EB) rates - were considered a cluster for the final analysis. We obtained Child Opportunity Index (COI) scores for each ZIP code to determine if there were differences in: 1) ZIP codes with suicide deaths compared to ZIPs with no deaths 2) differences in distribution of suicide death rates across quintiles of COI. RESULTS: Scan statistic identified 25 ZIP codes within a cluster (RR 2.6, P = 0.00066). Local Moran with EB rates identified two ZIP codes as a high-high cluster (P < 0.05). The location identified as a cluster in both approaches was in Alpine. The median COI for ZIP codes with suicide deaths was higher at 63.5 (IQR 38-83) compared to 47 (IQR 22.5-75.5) for ZIP codes without suicide deaths. There was a significant difference in suicide rates between Very Low and Moderate levels of Overall opportunity (P = .013). CONCLUSION: We identified a cluster of youth suicides in one of the most populous counties in the country. These findings serve to inform policies and prevention programs that aim to mitigate youth suicide mortality.

Performance of contrast-enhanced mammography for detecting multifocal and multicentric breast cancer and evaluating tumour size, and implications for surgical management: Early experience in a tertiary centre.

INTRODUCTION: To compare diagnostic accuracy of contrast-enhanced mammography (CEM) with standard 2D digital mammography (equivalent to low-energy image; LEM) for detection of multifocal and multicentric breast cancer and evaluation of tumour size and disease extent for preoperative planning. METHODS: Biopsy proven breast cancer patients who underwent CEM preoperatively between January 2021 and January 2023 were included in this study. CEM and LEM images were independently reviewed by at least two blinded readers. Lesion location, number, size (maximal diameter) and extension across the midline and/or nipple invasion were recorded. Tumour number and size estimated on imaging were compared with final operative histology, which served as the gold standard. RESULTS: Forty-nine patients (48 females and 1 male) and 50 cases (one patient had bilateral breast lesions) were included in the analysis. Median patient age was 60 (IQR 51, 69). CEM had significantly higher lesion detection rate compared with LEM, with sensitivities of 78% for LEM and 92% for CEM for the index tumour and 15% for LEM and 100% for CEM for multicentric and multifocal cancer. We found no statistically significant difference in median tumour size measurements on CEM and final surgical specimen (P value = 0.97); however, a significant difference was identified in the tumour size measured on LEM and surgical specimen (P value < 0.001). CONCLUSION: CEM is superior to standard 2D digital mammography for detection of multifocal and multicentric breast cancer and is a reliable and more accurate method for estimating tumour size.

Case Report: Disseminated Edwardsiella tarda infection in an immunocompromised patient.

Human infection caused by bacteria of the Edwardsiella genus is rare and most often presents with gastroenteritis that rarely requires antibiotics. Our case report describes a medically complex patient with chronic steroid use contributing to an immunocompromised state, who presented with fever and abdominal pain. The patient was later found to have Edwardsiella tarda (E. tarda) bacteremia and underwent paracentesis confirming E. tarda bacterial peritonitis requiring a prolonged antibiotic course. This case report aims to illustrate the presentation, diagnosis, and management of an uncommon infection that can have severe complications especially among immunocompromised patients.

Adolescent Experiences With Social Media and Suicidality.

OBJECTIVE: Examine social media experiences of the suicidal adolescent presenting to the emergency department with an acute mental health crisis. METHODS: We used qualitative interviews to obtain in-depth understanding of both negative and positive impacts of social media use on acute adolescent suicidal behavior. A bilingual transcriptionist transcribed audio recordings. Three investigators independently reviewed transcripts to identify themes and develop initial coding scheme through "open coding." Using grounded theory, data collection proceeded along with cultivation of themes until thematic saturation was achieved. Thematic saturation was determined when no new themes were generated from the data. Data were coded in Dedoose software to facilitate reporting of themes and quotes. Techniques to ensure trustworthiness included iterative data collection, use of a coding framework, and multiple coders. RESULTS: Seventeen interviews were conducted from May to October 2020. Median participant age was 15 years. Twenty-four percent were of Hispanic ethnicity and 82% identified as cisgender. Major themes include distraction from negative emotions; facilitated communication resulting in improved social connectedness; metric of connectedness; comparison of self to others; and desensitization and normalization to suicidal acts. Minor theme of increased time on social media is also discussed. These themes echoed components of current suicide theory. CONCLUSIONS: Acutely suicidal adolescents report social media experiences that reflect themes of social alienation and learned capacity for suicidal acts. Themes echo components of current suicide theory. Our participants also reported positive uses of social media. These protective experiences should be leveraged to inform strategies to interrupt behaviors leading to acute suicidality.

Complete resolution of rectal cancer with liver metastases after palliative chemoradiotherapy and unplanned surgical resection-a case report.

Metastatic colorectal cancer has poor prognosis for many patients at time of diagnosis with <20% 5-year survival rate. Recent advancements in palliative chemotherapy have improved patient outcomes as median survival has increased almost 2-fold. We report a 44-year-old gentleman who initially underwent palliative chemoradiotherapy and subsequently a Hartmann's procedure for ypT3N1M1 upper rectal adenocarcinoma with multiple liver metastases. Fortuitously, he made a remarkable recovery with complete radiological resolution of liver metastasis post-operatively. The patient has remained in remission for the past 10 years.

Geographic Variation in Acute Pediatric Mental Health Utilization.

OBJECTIVE: To identify locations with higher need for acute pediatric mental health (MH) interventions or services and describe these communities' socio-demographic characteristics. METHODS: This single-center retrospective study included patients 5 to 18 years old with an emergency department (ED) or hospital admission between 2017 and 2019 for a primary known MH diagnosis or symptoms. We extracted visit data from the electronic medical record, mapped patients to their home census tract, calculated normalized visit rates by census tract, and performed spatial analysis to identify nonrandom geographic clusters and outliers of high utilization. Census tract utilization rates were stratified into quartiles, and socioeconomic and demographic characteristics obtained from the US Census Bureau were compared using analysis of variance, chi-square tests, and multivariable analysis. RESULTS: There were 10,866 qualifying visits across 617 census tracts. ED and hospital admission rates ranged from 2.7 to 428.6 per 1000 children. High utilization clusters localized to neighborhoods with lower socioeconomic status (p < .05). Southern regions with high utilizers were more likely to have fewer children per neighborhood, higher rates of teen births, and lower socioeconomic status. Multivariate analysis showed regions with high utilizers had fewer children per neighborhood, lower median household income, and more families that lacked computer access. CONCLUSION: ED and hospital utilization for pediatric MH concerns varied significantly by neighborhood and demographics. Divergent social factors map onto these locations and are related to MH utilization. Leveraging geography can be a powerful tool in the development of targeted, culturally tailored interventions to decrease acute pediatric MH utilization and advance child MH equity.

Mediating Role of Fine Particles Abatement on Pediatric Respiratory Health During COVID-19 Stay-at-Home Order in San Diego County, California.

Lower respiratory tract infections disproportionately affect children and are one of the main causes of hospital referral and admission. COVID-19 stay-at-home orders in early 2020 led to substantial reductions in hospital admissions, but the specific contribution of changes in air quality through this natural experiment has not been examined. Capitalizing on the timing of the stay-at-home order, we quantified the specific contribution of fine-scale changes in PM2.5 concentrations to reduced respiratory emergency department (ED) visits in the pediatric population of San Diego County, California. We analyzed data on pediatric ED visits (n = 72,333) at the ZIP-code level for respiratory complaints obtained from the ED at Rady Children's Hospital in San Diego County (2015-2020) and ZIP-code level PM2.5 from an ensemble model integrating multiple machine learning algorithms. We examined the decrease in respiratory visits in the pediatric population attributable to the stay-at-home order and quantified the contribution of changes in PM2.5 exposure using mediation analysis (inverse of odds ratio weighting). Pediatric respiratory ED visits dropped during the stay-at-home order (starting on 19 March 2020). Immediately after this period, PM2.5 concentrations, relative to the counterfactual values based in the 4-year baseline period, also decreased with important spatial variability across ZIP codes in San Diego County. Overall, we found that decreases in PM2.5 attributed to the stay-at-home order contributed to explain 4% of the decrease in pediatric respiratory ED visits. We identified important spatial inequalities in the decreased incidence of pediatric respiratory illness and found that brief decline in air pollution levels contributed to a decrease in respiratory ED visits.

Spatial-temporal clusters of pediatric perforated appendicitis in California.

BACKGROUND: Perforated appendicitis is a well-documented child health disparity. Geographic patterns in perforated appendicitis exist in several United States regions, but such patterns have not been described in California. We aimed to analyze spatial-temporal patterns of pediatric perforated appendicitis and identify population characteristics contributing to these cluster patterns. METHODS: We geocoded risk-adjusted perforated appendicitis rates per 1000 appendicitis cases in patients 1-17 years from 2005-2015 in California. We performed a space-time cube analysis to identify hot spot trends. We performed logistic regression to estimate rural classification associated with spatial-temporal hot spots and multivariate analysis to assess effects of socioeconomic factors. RESULTS: In 2005-2015, 43,888 cases of pediatric perforated appendicitis occurred in California. Median risk-adjusted perforated appendicitis rate was 312 per 1000 appendicitis cases. We identified 11 spatial-temporal hot spots of perforated appendicitis. Rural micropolitan counties had 14 times higher odds of being classified as a hot spot (p<0.05, 95% CI 1-185). Poverty was a significant predictor of high perforated appendicitis median risk-adjusted rate (p<0.004). CONCLUSIONS: We identified 11 California hot spots of perforated appendicitis that persisted across a ten-year time span. Incorporating geography alongside our understanding of socioeconomic factors is a critical step in addressing this important child health disparity.

First-in-Human Study of the Biodistribution and Pharmacokinetics of 89Zr-CX-072, a Novel Immunopet Tracer Based on an Anti-PD-L1 Probody.

PURPOSE: CX-072, a PD-L1-targeting Probody therapeutic, is engineered to be activated by tumor proteases that remove a masking peptide. To study effects on biodistribution and pharmacokinetics, we performed 89Zr-CX-072 positron emission tomography (PET) imaging. EXPERIMENTAL DESIGN: Patients received ∼1 mg, 37 MBq 89Zr-CX-072 plus 0, 4, or 9 mg unlabeled CX-072 and PET scans at days 2, 4, and 7. After that, treatment comprised 10 mg/kg CX-072 q2 weeks (n = 7) + 3 mg/kg ipilimumab q3w 4× (n = 1). Normal organ tracer uptake was expressed as standardized uptake value (SUV)mean and tumor uptake as SUVmax. PD-L1 expression was measured immunohistochemically in archival tumor tissue. RESULTS: Three of the eight patients included received 10-mg protein dose resulting in a blood pool mean SUVmean ± SD of 4.27 ± 0.45 on day 4, indicating sufficient available tracer. Tumor uptake was highest at day 7, with a geometric mean SUVmax 5.89 (n = 113) and present in all patients. The median follow-up was 12 weeks (4-76+). One patient experienced stable disease and two patients a partial response. PD-L1 tumor expression was 90% in one patient and ≤1% in the other patients. Mean SUVmean ± SD day 4 at 10 mg in the spleen was 8.56 ± 1.04, bone marrow 2.21 ± 0.46, and liver 4.97 ± 0.97. Four patients out of seven showed uptake in normal lymph nodes and Waldeyer's ring. The tracer was intact in the serum or plasma. CONCLUSIONS: 89Zr-CX-072 showed tumor uptake, even in lesions with ≤1% PD-L1 expression, and modest uptake in normal lymphoid organs, with no unexpected uptake in other healthy tissues.

Conditional PD-1/PD-L1 Probody Therapeutics Induce Comparable Antitumor Immunity but Reduced Systemic Toxicity Compared with Traditional Anti-PD-1/PD-L1 Agents.

Immune-checkpoint blockade has revolutionized cancer treatment. However, most patients do not respond to single-agent therapy. Combining checkpoint inhibitors with other immune-stimulating agents increases both efficacy and toxicity due to systemic T-cell activation. Protease-activatable antibody prodrugs, known as Probody therapeutics (Pb-Tx), localize antibody activity by attenuating capacity to bind antigen until protease activation in the tumor microenvironment. Herein, we show that systemic administration of anti-programmed cell death ligand 1 (anti-PD-L1) and anti-programmed cell death protein 1 (anti-PD-1) Pb-Tx to tumor-bearing mice elicited antitumor activity similar to that of traditional PD-1/PD-L1-targeted antibodies. Pb-Tx exhibited reduced systemic activity and an improved nonclinical safety profile, with markedly reduced target occupancy on peripheral T cells and reduced incidence of early-onset autoimmune diabetes in nonobese diabetic mice. Our results confirm that localized PD-1/PD-L1 inhibition by Pb-Tx can elicit robust antitumor immunity and minimize systemic immune-mediated toxicity. These data provide further preclinical rationale to support the ongoing development of the anti-PD-L1 Pb-Tx CX-072, which is currently in clinical trials.

Aligning Partners in Pediatric Health: Using Geographical Information Systems to Plan Community Coalitions.

Introduction: Compared with adults, children have higher emergency department (ED) utilization for asthma exacerbation. While community coalitions have been shown to prevent ED visits for asthma, there is little guidance on where to best implement these efforts. Geographical information systems (GIS) technology can help in the selection and coordination of potential coalition partners. This report proposes a model to be used by clinicians and child health equity advocates to strategize high-impact community health interventions. The aims were to identify the clusters of ED utilization for pediatric asthma, evaluate sociodemographic features of the population within the clusters, and identify potential primary care and school community partners. Methods: This model uses ED visit data from 450 nonmilitary California hospitals in 2012. We obtained ZIP code-level counts and rates for patients younger than 18 years discharged with a diagnosis code of 493 for asthma conditions from the California Office of Statewide Health Planning and Development's Open Portal. We applied GIS spatial analysis techniques to identify statistically significant cluster for pediatric asthma ED utilization. We then locate the candidate community partners within these clusters. Results: There were 181 720 ED visits for asthma for all age groups in 2012 with 70 127 visits for children younger than 18 years. The top 3 geographic clusters for ED utilization rates were located in Fresno, Inglewood, and Richmond City, respectively. Spatial analysis maps illustrate the schools located within 0.5- and 1-mile radii of primary care clinics and provide a visual and statistical description of the population within the clusters. Conclusion: This study demonstrates a model to help clinicians understand how GIS can aid in the selection and creation of coalition building. This is a potentially powerful tool in the addressing child health disparities.