Faculty Bibliography

Food allergy therapy has experienced rapid growth over the past five years. In addition to avoidance measures and reactive treatment of accidental exposures, physicians can now offer patients multiple therapies for reducing the risk of severe reactions upon accidental exposure, and potentially achieving sustained remission. Many promising therapies are also in the pipeline. In this review, we outline the clinical management of food allergy, including mainstream non-pharmaceutical therapies, such as food oral immunotherapy (OIT), as well as three FDA-approved therapies: Palforzia (pharmaceutical peanut oral immunotherapy), omalizumab (anti-IgE monoclonal antibody), and Neffy (intranasal epinephrine). We also discuss emerging therapies, including novel routes of immunotherapy administration (epicutaneous, subcutaneous, sublingual, oral mucosal) and existing immunomodulatory therapies undergoing trials for use in food allergy, including dupilumab (anti-IL-4 and IL-13 monoclonal antibody), abrocitinib (oral JAK inhibitor) and abatacept (IgG-CTLA-4 fusion protein).

High-density microelectrode arrays have opened new possibilities for systems neuroscience, but brain motion relative to the array poses challenges for downstream analyses. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from action potential data, DREDge enables automated, high-temporal-resolution motion tracking in local field potential data. In human intraoperative recordings, DREDge's local field potential-based tracking reliably recovered evoked potentials and single-unit spike sorting. In recordings of deep probe insertions in nonhuman primates, DREDge tracked motion across centimeters of tissue and several brain regions while mapping single-unit electrophysiological features. DREDge reliably improved motion correction in acute mouse recordings, especially in those made with a recent ultrahigh-density probe. Applying DREDge to recordings from chronic implantations in mice yielded stable motion tracking despite changes in neural activity between experimental sessions. These advances enable automated, scalable registration of electrophysiological data across species, probes and drift types, providing a foundation for downstream analyses of these rich datasets.

OBJECTIVE:Demonstrate a successful laparoscopic removal of endometriosis from within the inguinal canal via a step-by-step video explanation, underscore the importance of pre-operative MRI imaging, and provide education on anatomy and surgical technique. DESIGN/METHODS:Video case presentation of a successful laparoscopic removal of endometriosis from within the inguinal canal. SUBJECTS/METHODS:A single patient with MRI imaging revealing endometriosis invasion into the inguinal canal and local vasculature. The patient included in this video gave consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, etc.) and other applicable sites. EXPOSURE/METHODS:The patient's abdomen was entered and vasculature was identified to prevent major bleeding. Appropriate exposure was achieved by transecting the round ligament to provide a landmark for the inguinal canal. The endometriosis was identified and dissected off the external iliac vasculature and the abdominal wall using the squeeze technique. The endometriosis was then dissected out of the inguinal canal, off the femoral artery, and then removed from the abdomen. Post-operatively, the patient was started on norethindrone acetate to suppress any residual disease and prevent recurrence. MAIN OUTCOME MEASURE/METHODS:Patient's pain and quality of life post-operatively. RESULTS:The patient noted immediate pain relief in the recovery room. One year post-operatively, the patient continued to endorse pain relief and no signs of hernia. CONCLUSION/CONCLUSIONS:Inguinal canal endometriosis is of rare occurrence. It typically presents as a groin lump or pain that is worse with menstruation. As the endometriosis is in close proximity to the abdominal wall and local vasculature, MRI imaging, as well as general surgery and vascular surgery consultation, are necessary for proper surgical planning. These are difficult operations that require proper understanding of pelvic and inguinal canal anatomy.

Gastrointestinal (GI) colonization by methicillin-resistant Staphylococcus aureus (MRSA) is associated with a high risk of transmission and invasive disease in vulnerable populations. The immune and microbial factors that permit GI colonization remain unknown. Male sex is correlated with enhanced Staphylococcus aureus nasal carriage, skin and soft tissue infections, and bacterial sepsis. Here, we established a mouse model of sexual dimorphism during GI colonization by MRSA. Our results show that in contrast to male mice that were susceptible to persistent colonization, female mice rapidly cleared MRSA from the GI tract following oral inoculation in a manner dependent on the gut microbiota. This colonization resistance displayed by female mice was mediated by an increase in IL-17A+ CD4+ T cells (Th17) and dependent on neutrophils. Ovariectomy of female mice increased MRSA burden, but gonadal female mice that have the Y chromosome retained enhanced Th17 responses and colonization resistance. Our study reveals a novel intersection between sex and gut microbiota underlying colonization resistance against a major widespread pathogen.

BACKGROUND:Children born very preterm (VPT) are at high risk for attention problems. This study's purpose was to describe the Conners Kiddie Continuous Performance Test (K-CPT) assessment in children born VPT, including rates of clinically elevated scores, change over time, and associations between K-CPT scores and parent reported attention problems. METHODS:We studied 305 children from a multi-site study of children born VPT who completed at least one K-CPT assessment at age 5, 6, and/or 7 years. Parent-reported ADHD symptoms and diagnosis were also collected. We calculated K-CPT completion rates, mean scores, and rates of clinically elevated scores at each timepoint. Linear mixed models examined change over time in K-CPT scores. Correlations and generalized linear models investigated associations between K-CPT scores and ADHD symptoms and diagnoses. RESULTS:K-CPT scores showed expected age-related improvements from age 5-7, with significant intra- and inter-individual variability. Up to 1/3 of children had clinically elevated attention problems and another 1/3 had subclinical elevations. K-CPT scores were modestly correlated with parent-rated ADHD symptoms and children with a parent-reported ADHD diagnosis performed worse on nearly all K-CPT metrics. CONCLUSION/CONCLUSIONS:Performance-based measures like the K-CPT can be useful for research and clinical practice in VPT populations. IMPACT/CONCLUSIONS:Attention problems are a specific area of weakness for children born very preterm. Performance-based tests of attention have benefits and drawbacks compared to parent report measures yet are understudied in this population. We examined one performance-based measure (the Conners Kiddie Continuous Performance Test [K-CPT]) in 305 children born very preterm. We observed improving task scores from age 5-7 years with significant intra- and inter-individual variability, a sizable proportion of children with clinically and subclinically elevated scores, and modest associations between K-CPT scores and parent reported attention problems. The K-CPT could be a useful clinical and research tool in this population.

BACKGROUND AND PURPOSE/OBJECTIVE:Perfusion and perfusion-related parameter maps obtained using dynamic susceptibility contrast (DSC) MRI and dynamic contrast enhanced (DCE) MRI are both useful for clinical diagnosis and research. However, using both DSC and DCE MRI in the same scan session requires two doses of gadolinium contrast agent. The objective was to develop deep-learning based methods to synthesize DSC-derived parameter maps from DCE MRI data. MATERIALS AND METHODS/METHODS:Independent analysis of data collected in previous studies was performed. The database contained sixty-four participants, including patients with and without brain tumors. The reference parameter maps were measured from DSC MRI performed following DCE MRI. A conditional generative adversarial network (cGAN) was designed and trained to generate synthetic DSC-derived maps from DCE MRI data. The median parameter values and distributions between synthetic and real maps were compared using linear regression and Bland-Altman plots. RESULTS:Using cGAN, realistic DSC parameter maps could be synthesized from DCE MRI data. For controls without brain tumors, the synthesized parameters had distributions similar to the ground truth values. For patients with brain tumors, the synthesized parameters in the tumor region correlated linearly with the ground truth values. In addition, areas not visible due to susceptibility artifacts in real DSC maps could be visualized using DCE-derived DSC maps. CONCLUSIONS:DSC-derived parameter maps could be synthesized using DCE MRI data, including susceptibility-artifact-prone regions. This shows the potential to obtain both DSC and DCE parameter maps from DCE MRI using a single dose of contrast agent. ABBREVIATIONS/BACKGROUND:=plasma volume.

IMPORTANCE/UNASSIGNED:It remains unclear whether children and adolescents with SARS-CoV-2 infection are at heightened risk for long-term kidney complications. OBJECTIVE/UNASSIGNED:To investigate whether SARS-CoV-2 infection is associated with an increased risk of postacute kidney outcomes among pediatric patients, including those with preexisting kidney disease or acute kidney injury (AKI). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study used data from 19 health institutions in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) initiative from March 1, 2020, to May 1, 2023 (follow-up ≤2 years completed December 1, 2024; index date cutoff, December 1, 2022). Participants included children and adolescents (aged <21 years) with at least 1 baseline visit (24 months to 7 days before the index date) and at least 1 follow-up visit (28 to 179 days after the index date). EXPOSURES/UNASSIGNED:SARS-CoV-2 infection, determined by positive laboratory test results (polymerase chain reaction, antigen, or serologic) or relevant clinical diagnoses. A comparison group included children with documented negative test results and no history of SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Outcomes included new-onset chronic kidney disease (CKD) stage 2 or higher or CKD stage 3 or higher among those without preexisting CKD; composite kidney events (≥50% decline in estimated glomerular filtration rate [eGFR], eGFR ≤15 mL/min/1.73 m2, dialysis, transplant, or end-stage kidney disease diagnosis), and at least 30%, 40%, or 50% eGFR decline among those with preexisting CKD or acute-phase AKI. Hazard ratios (HRs) were estimated using Cox proportional hazards regression models with propensity score stratification. RESULTS/UNASSIGNED:Among 1 900 146 pediatric patients (487 378 with and 1 412 768 without COVID-19), 969 937 (51.0%) were male, the mean (SD) age was 8.2 (6.2) years, and a range of comorbidities was represented. SARS-CoV-2 infection was associated with higher risk of new-onset CKD stage 2 or higher (HR, 1.17; 95% CI, 1.12-1.22) and CKD stage 3 or higher (HR, 1.35; 95% CI, 1.13-1.62). In those with preexisting CKD, COVID-19 was associated with an increased risk of composite kidney events (HR, 1.15; 95% CI, 1.04-1.27) at 28 to 179 days. Children with acute-phase AKI had elevated HRs (1.29; 95% CI, 1.21-1.38) at 90 to 179 days for composite outcomes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this large US cohort study of children and adolescents, SARS-CoV-2 infection was associated with a higher risk of adverse postacute kidney outcomes, particularly among those with preexisting CKD or AKI, suggesting the need for vigilant long-term monitoring.

BACKGROUND:The HIV/AIDS epidemic remains critical in sub-Saharan Africa, with UNAIDS establishing "95-95-95" targets to optimize HIV care. Using the 2020 Zimbabwe Population-based HIV Impact Assessment (ZIMPHIA) geospatial data, this study aimed to identify patterns in these targets and determinants impacting the HIV care continuum in underserved Zimbabwean communities. METHODS:Analysis techniques, including Gaussian kernel interpolation, optimized hotspot, and multivariate geospatial k-means clustering, were utilized to establish spatial patterns and cluster regional HIV care continuum needs. Further, we investigated healthcare availability, access, and social determinants and scrutinized the association between socio-demographic and behavioral covariates with HIV care outcomes. RESULTS:Disparities in progress toward the "95-95-95" targets were noted across different regions, with each target demonstrating unique geographic patterns, resulting in four distinct clusters with specific HIV care needs. Key factors associated with gaps in achieving targets included younger age, male gender, employment, and minority or no religious affiliation. CONCLUSIONS:Our study uncovers significant spatial heterogeneity in the HIV care continuum in Zimbabwe, with unique regional patterns in "95-95-95" targets. The spatial analysis of the UNAIDS targets presented here could prove instrumental in designing effective control strategies by identifying vulnerable communities that are falling short of these targets and require intensified efforts. We provide insights for designing region-specific interventions and enhancing community-level factors, emphasizing the need to address regional gaps and improve HIV care outcomes in vulnerable communities that lag behind.

Primary brain tumors are the most common solid tumor and cause of cancer-related deaths in children. Their clinical presentation depends on the age of the child and the location of tumor. Tumors in infancy often present with nonspecific symptoms, while focal neurological symptoms are more evident in older children. In this article, we review the most common acute neurological effects of pediatric primary brain tumors and their treatments.