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BACKGROUND: Most tympanic membrane (TM) perforations heal spontaneously, but 10%-20% remain chronic and might lead to impaired hearing and recurrent middle ear infections. Alpha1-antitrypsin (AAT) is a circulating tissue-protective protein that is elevated under inflammatory conditions and is currently indicated for genetic AAT deficiency. Recently, AAT has been shown to promote tissue remodeling and inflammatory resolution. OBJECTIVE: This study aimed to examine the effects of local clinical-grade AAT treatment on tissue repair in a mouse model of acute traumatic TM perforation. METHODS: Wild-type mice underwent unilateral TM perforation and were either left untreated or treated locally with human AAT (9 × 10-3 mL at 20 mg/mL on days 0, 1, and 2; n = 15/group). The perforations were evaluated macroscopically on a serial basis. Mice were sacrificed on various days post-injury, and TMs were excised for gene analysis by RT-PCR. RESULTS: There were no adverse reactions in hAAT-treated ears throughout the study period. Compared with untreated animals, TM closure occurred earlier in the treated group (days until full closure, median: 4 and 9, respectively). According to gene expression analysis, VEGF, TGFß, and collagen-5A1 were induced earlier in AAT-treated mice (day 4-5 compared with day 9). Additionally, IL-10 expression levels were higher and IL-6 levels were lower in treated versus untreated mice. CONCLUSION: A local tissue environment rich in AAT promotes early tissue repair in a perforated TM model both macroscopically and molecularly. Studies are underway to examine TM functionality and recombinant AAT formulations for micro-dosing in the format of a single local application. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.
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INTRODUCTION: Necrotizing otitis externa (NOE) is a serious, progressive, and potentially life-threatening infection of the external auditory canal, affecting soft tissue and bone. The most common organism causing NOE is Pseudomonas Aeruginosa and less common are Fungal infections. When managing a patient with NOE, a culture is taken from the EAC in order to tailor the appropriate antimicrobial treatment, however commonly, the culture is sterile. Inflammation biomarkers may be used as adjuncts to inform on the differential diagnosis and as prognostic markers. AIM: To characterize and compare values and ratios of components of the complete blood count (CBC) at admission, at patients with positive swab culture. METHODS: A retrospective study of NOE patients was conducted. We included all patients admitted between the years 2001-2023, for whom a culture swab tested positive. We compared CBC findings at hospitalization between bacteria and fungi-positive culture patients. RESULTS: Eosinophils-to-Neutrophils Ratio (ENR) was significantly lower in the fungal group compared to the bacterial group 0.023 ± 0.02 and 0.04 ± 0.03, respectively (p-value = 0.025). Eosinophils-to-Leukocyte Ratio (ELR) was significantly lower in the fungal group compared to the bacterial group 0.058 ± 0.04 and 0.12 ± 0.1 respectively (p-value = 0.009). For definition of ELR ≤ 0.1 we found that, sensitivity was 88% (95%CI = 0.679-0.979) and NPV 90% (95%CI = 0.709-0.982). For definition of ENR ≤ 0.03 sensitivity was 88% (95%CI = 0.679-0.979) and NPV 88% (95%CI = 0.679-0.979). CONCLUSION: Lower values of ELR and ENR in patients with NOE are associated with fungal infection and can serve as a tool in adjusting an appropriate antimicrobial therapy in cases of sterile or when no culture is available.