Diagnostic accuracy of eosinophil-to-lymphocyte ratio and eosinophil-to-neutrophil ratio as biomarkers for differentiating between fungal and bacterial infection in necrotising otitis externa.

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.

Acute otitis media in the first two months of life and the impact of pneumococcal conjugate vaccines: A retrospective cohort study.

BACKGROUND: Information on pneumococcal vaccination's impact on the prevention of acute otitis media (AOM) at very young ages is limited. OBJECTIVES: To define the trends in tympanocentesis-proven AOM incidence, clinical characteristics, microbiology, and antibiotic resistance in infants <2 months of age in southern Israel, before and after the sequential introduction of 7- and 13-valent PCVs. METHODS: A retrospective population-based cohort study including children <2 months of age diagnosed with AOM at the pediatric emergency room between January 2005-Decmber 2009 (pre-vaccination group, group 1) and January 2013-July 2021 (post-PCV13 introduction, group 2). RESULTS: 160 patients were enrolled, 89 (55.6%) in group 1 and 71 (44.4%) in group 2. The mean incidence of AOM decreased from 1.2 cases/1000 live births for group 1 to 0.45 cases/1000 live births for group 2, P < 0.001.130 (81.25%) patients were hospitalized, with higher hospitalization rates in group 1 vs. group 2 (84/89, 94% vs. 46/71, 65%, P < 0.001). Hospitalization length was longer in group 1 vs. group 2 (4.07 ± 4.09 days vs. 2.70 ± 1.82 days, P = 0.021). Positive MEF cultures were reported in 94/160 (58.75%) patients, with a decrease in positivity rates between the 2 groups (71/89, 80% vs. 23/71, 32%, P < 0.001). S. pneumoniae was the most common pathogen (55/94, 58.5%); it was the most frequent pathogen isolated in group 1 (46/71, 65%), and the second most common pathogen in group 2 (9/23, 39%), P = 0.03. A significant increase was recorded in the percentages of patients with negative MEF cultures (from 21% to 68%, P < 0.001). CONCLUSIONS: The introduction and implementation of PCV13 in southern Israel was associated with a decrease in AOM in children <2 months of age and of S. pneumoniae recovery in these patients and was accompanied by less admissions and shorter hospitalizations. An increase in the proportions of negative bacterial cultures from MEF was recorded during the study period.

Tumor Tissue Explant Culture of Patient-Derived Xenograft as Potential Prioritization Tool for Targeted Therapy.

Despite of remarkable progress made in the head and neck cancer (HNC) therapy, the survival rate of this metastatic disease remain low. Tailoring the appropriate therapy to patients is a major challenge and highlights the unmet need to have a good preclinical model that will predict clinical response. Hence, we developed an accurate and time efficient drug screening method of tumor ex vivo analysis (TEVA) system, which can predict patient-specific drug responses. In this study, we generated six patient derived xenografts (PDXs) which were utilized for TEVA. Briefly, PDXs were cut into 2 × 2 × 2 mm3 explants and treated with clinically relevant drugs for 24 h. Tumor cell proliferation and death were evaluated by immunohistochemistry and TEVA score was calculated. Ex vivo and in vivo drug efficacy studies were performed on four PDXs and three drugs side-by-side to explore correlation between TEVA and PDX treatment in vivo. Efficacy of drug combinations was also ventured. Optimization of the culture timings dictated 24 h to be the time frame to detect drug responses and drug penetrates 2 × 2 × 2 mm3 explants as signaling pathways were significantly altered. Tumor responses to drugs in TEVA, significantly corresponds with the drug efficacy in mice. Overall, this low cost, robust, relatively simple and efficient 3D tissue-based method, employing material from one PDX, can bypass the necessity of drug validation in immune-incompetent PDX-bearing mice. Our data provides a potential rationale for utilizing TEVA to predict tumor response to targeted and chemo therapies when multiple targets are proposed.