Histopathologic features of biologic therapy nonresponders in chronic rhinosinusitis with nasal polyposis.

BACKGROUND: Biologics are effective for chronic rhinosinusitis with nasal polyposis (CRSwNP) by reducing type 2 inflammation. Nonresponders often require functional endoscopic sinus surgery (FESS) and represent a challenging population potentially due to non-type 2 pathophysiology. This study characterizes the histopathologic features of biologic nonresponders. METHODS: A retrospective review of 257 CRSwNP patients undergoing FESS was conducted. The biologic nonresponder group included patients with prior biologic therapy who exhibited persistent symptoms and polyp burden. Those with CRSwNP not prescribed biologic therapy were selected as controls. Demographics, comorbidities, and structured histopathology consisting of 13 variables were collected. RESULTS: Of 257 CRSwNP patients, 20 were on biologics prior to FESS. Fourteen patients (70.0%) received dupilumab, one (5.0%) received mepolizumab, one (5.0%) received omalizumab, and four (20.0%) tried multiple biologics. The mean age for the biologic nonresponder group was 45.8 years compared to 50.4 years for the controls. Nonresponders had a significantly increased incidence of reduced tissue eosinophilia, defined as <5 per high power field (55% vs. 31.2%, p = 0.044) and increased basement membrane thickening (100% vs. 78.1%, p = 0.019). The remaining 11 variables did not reach statistical significance. CONCLUSION: Histopathologic analysis of biologic nonresponders demonstrates decreased eosinophilia and thickened basement membranes. These findings, particularly low tissue eosinophils, are consistent with a non-type 2 CRSwNP that may be recalcitrant to biologic therapies. Histopathologic analysis done in conjunction with FESS may aid clinicians in understanding response to biologic therapies in patients with CRSwNP who have persistent symptom burden necessitating FESS.

Peritonsillar Abscess Size as a Predictor of Medical Therapy Success.

OBJECTIVE: To evaluate the success of sole medical therapy (MT) versus surgical therapy (ST) in patients with both clinically and radiographically confirmed peritonsillar abscess (PTA). To also determine treatment safety based on abscess size, and identify predictors of treatment failure. METHODS: This was a retrospective cohort of 3 hospitals in a single academic health system. A total of 214 immunocompetent patients diagnosed with uncomplicated PTA underwent a contrasted CT scan of the neck. About 87 patients were treated with sole MT (intravenous antibiotics and steroids), and 127 patients were treated with ST (MT plus drainage). RESULTS: Treatment failure occurred in 8.0% of the MT group and 7.9% of the ST group (P = 1.00). In PTAs <2 cm, treatment failure occurred in 5.3% of the MT group and 5.0% of the ST group (P = 1.00). In PTAs ≥2 cm, treatment failure occurred in 13.3% of the MT group and 9.0% treated with ST (P = .53). Size ≥2 cm (OR - 3.46, P = .08) and IV clindamycin as sole IV antibiotic (OR - 2.46, P = .15) trended toward predicting treatment failure. In addition to those considered failures, 7.0% of the ST group returned to the ED with pain versus 0% of the MT group (P = .01). CONCLUSION: Frequency of treatment failure was not significantly different among patients receiving MT and ST. Abscesses ≥2 cm in size were more likely to fail in both groups and ST was not statistically superior. Sole MT for uncomplicated PTA may help reduce unnecessary procedures and healthcare costs.

Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway.

Neuronal activity regulates the phosphorylation states at multiple sites on MeCP2 in postmitotic neurons. The precise control of the phosphorylation status of MeCP2 in neurons is critical for the normal development and function of the mammalian brain. However, it is unknown whether phosphorylation at any of the previously identified sites on MeCP2 can be induced by signals other than neuronal activity in other cell types, and what functions MeCP2 phosphorylation may have in those contexts. Here we show that in neural progenitor cells isolated from the adult mouse hippocampus, cell cycle-linked phosphorylation at serine 421 on MeCP2 is directly regulated by aurora kinase B and modulates the balance between proliferation and neural differentiation through the Notch signalling pathway. Our findings suggest MeCP2 S421 phosphorylation may function as a general epigenetic switch accessible by different extracellular stimuli through different signalling pathways for regulating diverse biological functions in different cell types.