Pediatric Invasive Fungal Rhinosinusitis: A Comprehensive Analysis of Prognostic Factors for Survival.

OBJECTIVE: Pediatric invasive fungal rhinosinusitis (IFS) is a devastating infection that manifests almost exclusively in immunocompromised children. The goal of this work was to determine which clinical features carry prognostic value for survival. METHODS: A retrospective review of children with a histopathological diagnosis of IFS was performed at an academic tertiary care institution from 1990 to 2021. Clinical variables were collected to generate survival and life-table estimators at 6-months and 1-year. RESULTS: Eighteen patients were included in this analysis, with a mean age of 9.8 years (range, 1-17 years). Most children were neutropenic (n = 15, 83.3%), with acute lymphoblastic leukemia (n = 10, 55.6%) representing the most common primary diagnosis. A mean of 3.2 operations (range 1-7 operations) was performed per patient for either mucormycosis (n = 10, 55.6%) or aspergillosis (n = 8, 44.4%). The mean time to absolute neutrophil count recovery was 65.8 days (range 20-137 days), with a 6-month and 1-year survival rate of 47.6% and 41.7%, respectively. Gross total resection (p = 0.006, p < 0.001), number of antifungals (p = 0.0004, p = 0.0003), and total operation number (p = 0.0032, p = 0.0035), served as positive prognostic factors for 6-month and 1-year survival. Conversely, altered mental status (p = 0.0026), cerebral involvement (p = 0.0010), cranial neuropathies (p < 0.0001), hyperglycemia (p = 0.0445, p = 0.0208), and intensive care unit status (p = 0.0013) served as negative prognostic factors for 6-month and 1-year survival. CONCLUSION: Several key elements were identified and found to play a vital role in influencing survival for pediatric IFS. Early diagnosis, prompt medical therapy, and aggressive surgical intervention remain at the forefront in the treatment of this complex opportunistic infection. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1239-1250, 2023.

The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord.

The mechanisms controlling the transition from neurogenesis to gliogenesis in the vertebrate CNS are incompletely understood. We identified a family of transcription factors, called NFI genes, which are induced throughout the spinal cord ventricular zone (VZ) concomitantly with the induction of GLAST, an early marker of gliogenesis. NFIA is both necessary and sufficient for GLAST induction in the VZ. Unexpectedly, NFIA is also essential for the continued inhibition of neurogenesis in VZ progenitors. This function is mediated by the requirement of NFIA for the expression of HES5, a Notch effector. However, Notch effectors are unable to promote glial-fate specification in the absence of NFIA. Thus, NFIA links the abrogation of neurogenesis to a generic program of gliogenesis, in both astrocyte and oligodendrocyte VZ progenitors. At later stages, NFIA promotes migration and differentiation of astrocyte precursors, a function that is antagonized in oligodendrocyte precursors by Olig2.

Biofilm and persistent inflammation in endoscopic sinus surgery.

Bacterial biofilms have been observed in many patients with chronic rhinosinusitis, but their importance is still being investigated. This study examines the association between biofilms and other clinical findings in chronic rhinosinusitis patients. Twenty-four patients with chronic rhinosinusitis who failed medical management underwent endoscopic sinus surgery (ESS). Tissue was collected from the ethmoid sinus and analyzed for the presence of biofilm by hematoxylin and eosin staining, fluorescent in situ hybridization, and confocal scanning laser microscopy. Biofilms were classified as extensive (> 50% of mucosal surface in sample) or present (< 50% of surface). The surgeon remained blinded to the biofilm status of patients until postoperative follow-up was complete. The presence of bacterial biofilm was strongly associated with persistent mucosal inflammation after ESS (53% of biofilm-positive patients vs 0% of biofilm-negative patients, P = 0.009). The amount of biofilm was not important as there was no significant difference between the extensive and present biofilm classifications with respect to inflammation. The presence of biofilm was not associated with prior ESS, allergies, eosinophils, polyps, or presence of fungal elements.

Biofilm detection with hematoxylin-eosin staining.

OBJECTIVE: To demonstrate that hematoxylin-eosin staining can be used to detect the presence of bacterial biofilm in patients with chronic rhinosinusitis (CRS). DESIGN: A prospective study. SETTING: The University of Southern California University Hospital and the Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Keck School of Medicine, Los Angeles. PATIENTS: A total of 34 patients: 24 undergoing endoscopic sinus surgery for CRS and 10 undergoing septoplasty with or without turbinate reduction with no history of sinusitis, were enrolled in the study. MAIN OUTCOME MEASURES: Contiguous sections from patient samples were examined by both hematoxylin-eosin staining and fluorescence in situ hybridization (FISH) with the bacterial-specific probe EUB338 for evidence of bacterial biofilm. RESULTS: Biofilm was detected by hematoxylin-eosin staining in 15 of 24 patients with CRS and 1 of 10 control patients. In all cases, hematoxylin-eosin staining was found to be an accurate predictor of the presence or absence of biofilm using FISH as a control standard. CONCLUSION: Hematoxylin-eosin staining of surgical specimens is a reliable and available method for the detection of bacterial biofilm in chronic infectious disease.