Dual blockade of IL-4 and IL-13 with dupilumab ameliorates sensorineural olfactory dysfunction in mice with eosinophilic sinonasal inflammation.

BACKGROUND: Dupilumab, an antibody that binds IL-4Rα and inhibits IL-4 and IL-13 signals, has demonstrated efficacy in chronic rhinosinusitis with nasal polyps (CRSwNP) primarily characterized by type 2 inflammation. Current evidence suggests that the rate of improvement in olfactory dysfunction with dupilumab exceeds that of nasal polyp reduction, yet the underlying mechanism remains undisclosed. We hypothesize that dupilumab may initially ameliorate sensorineural olfactory dysfunction. METHODOLOGY: Male BALB/c mice were intranasally administered ovalbumin and Aspergillus protease for 12 weeks to induce eosinophilic sinonasal inflammation. Dupilumab treatment was also administered. The mice underwent histological assessment, olfactory behavioural test, and gene expression profiling to identify neuroinflammatory markers within the olfactory bulb. RESULTS: Dupilumab treatment resulted in a reduction in the number of mucosal protruding lesions, as well as decreased infiltration of eosinophils and neutrophils, along with a decrease in olfactory sensory neuron injury. Furthermore, there was a downregulation in the mRNA expression related to microglia activation and neuroinflammation in the olfactory bulb. CONCLUSIONS: Dupilumab improves the sensorineural pattern of olfactory dysfunction in mice, potentially explaining why olfaction improves more rapidly than polyp reduction in patients with CRSwNP.

Impaired thrombin generation in Reelin-deficient mice: a potential role of plasma Reelin in hemostasis.

BACKGROUND: Reelin is a large extracellular glycoprotein that is present in the peripheral blood. That Reelin interacts with the coagulation components and elicits a functional role in hemostasis has not yet been elucidated. OBJECTIVES: The hemostatic activity of Reelin is investigated and defined in this study. METHODS: The interplay of Reelin with coagulation components was elucidated by far-Western and liposome/platelet binding assays. In vivo and ex vivo hemostasis-related analyses of Reelin-deficient mice and plasma were also performed. RESULTS: Reelin interacted with the liposomes containing phosphatidylserine (PS) or phosphatidylcholine. Instead of interacting with known Reelin receptors (ApoE receptor 2, very low density lipoprotein receptor and integrin ß1), Reelin interacted with PS of the activated platelets. The interaction between Reelin and the coagulation factors of thrombin and FXa was also demonstrated with the Kd of 11.7 and 21.2 nm, respectively. Reelin-deficient mice displayed a prolonged bleeding time and an increase in rebleeding rate. Despite the fact that Reelin deficiency had no significant effect on the clotting time of prothrombin and activated partial thromboplastin time, the fibrin clot formation was abnormal and the fibrin clot structure was relatively loosened with reduced clot strength. Abnormal fibrinogen expression did not account for the hemostatic defects associated with Reelin deficiency. Instead, thrombin generation was impaired concomitant with an altered prothrombin cleavage pattern. CONCLUSIONS: By interacting with platelet phospholipids and the coagulation factors, thrombin and FXa, Reelin plays a selective role in coagulation activation, leading to thrombin generation and formation of a normal fibrin clot.

Klebsiella pneumoniae pharyngitis mimicking malignancy: a diagnostic dilemma.

Acute pharyngitis is a common disease. However, acute pharyngitis caused by Klebsiella pneumoniae with a gross appearance mimicking hypopharyngeal malignancy has never previously been reported. We report the case of a 57-year-old man with a right hypopharyngeal tumor which was disclosed by fiberoptic laryngoscopy and computed tomography scan. However, both the frozen and final pathologies showed no evidence of malignant cells, and a bacterial culture revealed the growth of K. pneumoniae. The hypopharyngeal lesion completely regressed after 2 weeks of antibiotic treatment. Clinicians should perform biopsy along with tissue culture for tumor-like lesions because infectious agents can lead to lesions with malignancy-like appearance.

Critical airway induced by formalin injection: case report.

BACKGROUND: Formalin is a saturated aqueous solution comprising 37-40 per cent formaldehyde. It is often used in histopathology laboratories as a tissue preservative. The ingestion or injection of formalin has an immediate, powerful and destructive impact on humans. This paper reports a case of formalin injection and reviews the relevant world literature. CASE REPORT: A 36-year-old male attempted suicide by injecting formalin into the right side of his neck, resulting in a critical airway situation. An endotracheal tube was inserted and a tracheostomy was then performed to secure his airway. After receiving medical treatment, including antibiotics and N-acetyl cysteine, the status of the patient's airway improved. CONCLUSION: When examining patients who have injected substances into their neck, the possibility of deep neck inflammation with airway compromise should be considered. Immediate management, which should include establishment of a definitive airway and prophylactic infection control, is crucial.