Resource Utilization and Risk Factors for Esophageal Injury in Pediatric Esophageal Foreign Bodies.

OBJECTIVE: While management protocols of pediatric esophageal foreign bodies (EFBs) are well-delineated, resource utilization can be improved. This study's objectives were to explore hospital charges/costs for pediatric patients who present with EFBs and to identify patient risk factors associated with esophageal injury. METHODS: A retrospective chart review of patients undergoing aerodigestive foreign body removal at a tertiary-care children's hospital from 2018 to 2021 was conducted. Data collected included demographics, medical history, presenting symptoms, EFB type, surgical findings, and hospital visit charges/costs. RESULTS: 203 patients were included. 178 of 203 (87.7%) patients were admitted prior to operation. Unwitnessed EFB ingestion (p < 0.001, OR = 15.1, 95% CI = 5.88-38.6), experiencing symptoms for longer than a week (p < 0.001, OR = 11.4, 95% CI = 3.66-38.6) and the following presenting symptoms increased the odds of esophageal injury: dysphagia (p = 0.04, OR = 2.45, 95% CI = 1.02-5.85), respiratory distress (p = 0.005, OR = 15.5, 95% CI = 2.09-181), coughing (p < 0.001, OR = 10.1, 95% CI = 3.73-28.2), decreased oral intake (p = 0.001, OR = 6.60, 95% CI = 2.49-17.7), fever (p = 0.001, OR = 5.52, 95% CI = 1.46-19.6), and congestion (p = 0.001, OR = 8.15, 95% CI = 2.42-27.3). None of the 51 asymptomatic patients had esophageal injury. The median total charges during the encounter was $20,808 (interquartile range: $18,636-$24,252), with operating room (OR) (median: $5,396; 28.2%) and inpatient admission (median: $5,520; 26.0%) contributing the greatest percentage. CONCLUSIONS: Asymptomatic patients with EFBs did not experience esophageal injury. The OR and inpatient observation accounted for the greatest percentage of the hospital charges. These results support developing a potential algorithm to triage asymptomatic patients to be managed on a same-day outpatient basis to improve the value of care. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

DAT and TH expression marks human Parkinson's disease in peripheral immune cells.

Parkinson's disease (PD) is marked by a loss of dopamine neurons, decreased dopamine transporter (DAT) and tyrosine hydroxylase (TH) expression. However, this validation approach cannot be used for diagnostic, drug effectiveness or investigational purposes in human patients because midbrain tissue is accessible postmortem. PD pathology affects both the central nervous and peripheral immune systems. Therefore, we immunophenotyped blood samples of PD patients for the presence of myeloid derived suppressor cells (MDSCs) and discovered that DAT+/TH+ monocytic MDSCs, but not granulocytic MDSCs are increased, suggesting a targeted immune response to PD. Because in peripheral immune cells DAT activity underlies an immune suppressive mechanism, we investigated whether expression levels of DAT and TH in the peripheral immune cells marks PD. We found drug naïve PD patients exhibit differential DAT+/TH+ expression in peripheral blood mononuclear cells (PBMCs) compared to aged/sex matched healthy subjects. While total PBMCs are not different between the groups, the percentage of DAT+/TH+ PBMCs was significantly higher in drug naïve PD patients compared to healthy controls irrespective of age, gender, disease duration, disease severity or treatment type. Importantly, treatment for PD negatively modulates DAT+/TH+ expressing PBMCs. Neither total nor the percentage of DAT+/TH+ PBMCs were altered in the Alzheimer's disease cohort. The mechanistic underpinning of this discovery in human PD was revealed when these findings were recapitulated in animal models of PD. The reverse translational experimental strategy revealed that alterations in dopaminergic markers in peripheral immune cells are due to the disease associated changes in the CNS. Our study demonstrates that the dopaminergic machinery on peripheral immune cells displays an association with human PD, with exciting implications in facilitating diagnosis and investigation of human PD pathophysiology.

A novel approach to study markers of dopamine signaling in peripheral immune cells.

Human monocytes express known markers of dopamine synthesis, storage and clearance, including dopamine transporter (DAT), tyrosine hydroxylase (TH), all subtypes of dopamine receptors and vesicular monoamine transporter 2 (VMAT2). Immunohistochemical and immunofluorescent methodologies have traditionally been employed to determine DAT and TH expression in the CNS, their detection in the blood and specifically in the peripheral monocytes has not been studied by flow cytometry. Flow cytometry assays are widely used in medicine and in basic, preclinical or clinical research to quantify physical and chemical characteristics of target cell populations. Here, we have established a highly sensitive and reproducible flow cytometry panel to detect and quantify DAT and TH expression in freshly isolated or cryopreserved human peripheral monocytes. In healthy humans (n = 41 biological replicates), we show baseline DAT and TH expressing monocytes constitute ~12% of the peripheral blood mononuclear cell (PBMC) fraction when examined in fresh isolation from whole blood. Using an identical flow cytometry panel, we found that cryopreservation of PBMCs using multiple techniques resulted in altered PBMC populations as compared to fresh isolation and relative to one another. Among these, we identified an optimum cryopreservation method for detecting TH and DAT in cryopreserved PBMCs. Our data provide a sensitive and reproducible approach to examine dopamine signaling in peripheral human immune cells. This approach can be applied to study peripheral dopamine signaling under healthy and potentially under disease conditions. The use of dopamine signaling could also be explored as a technique to monitor therapeutic interventions particularly those targeting DAT and TH in the periphery.