Pott's Puffy: First Shot is the Best Shot.

OBJECTIVE: Low incidence of Pott's Puffy tumor (PPT) has caused studying risk factors and recurrences of the disease to be difficult. We used the comparatively increased incidence at our institution to evaluate potential risk factors for the disease process itself and prognostic factors for recurrence of the disease. METHODS: Single institutional retrospective chart review identified 31 patients from 2010 to 2022 with PPT compared with a control group of 20 patients with either chronic rhinosinusitis or recurrent sinusitis. Patient mean age of PPT was 42 (range of 5 to 90) with the majority of the patient population as male (74%) and Caucasian (68%) in the setting of rural West Texas. Patient mean age of the control group was 50.7 (range of 30-78) with majority of patient population as male (55%) and Caucasian (70%). Interventions studied were functional endoscopic sinus surgery (FESS), FESS with trephination, and cranialization with or without FESS to compare prognostic factors for recurrence rates of PPT. These patients' prognostic risk factors for recurrence and risk factors to develop PPT were analyzed using Analysis of Variance (ANOVA) χ 2 statistical analysis with Fischer exact testing. RESULTS: Mean age was 42 years (range of 5-90) with the majority of the PPT patient population as male (74%) and Caucasian (68%) with an overall incidence of about 1 in 300,000. Pott's Puffy tumor patients were significantly favored in the younger and male population compared with the control patients. Risk factors of no prior allergy diagnosis, previous trauma, medication allergy to penicillin class or cephalosporin class, and lower body mass index were significant in the PPT population compared with the control group. Significant prognostic factors for recurrence of PPT were prior history of sinus surgery and operative treatment choice. Fifty percent (3/6) of patients with prior sinus surgery had recurrence of PPT. Of our 4 treatment options (FESS, FESS with trephination, FESS with cranialization, or cranialization alone), ;FESS had a recurrence of PPT of 0% (0/13), FESS with trephination had a recurrence of PPT of 50% (3/6), FESS with cranialization had a recurrence of PPT of 11% (1/9), and cranizalization alone had a recurrence of PPT of 0% (0/3). Of note, postop chronic rhinosinusitis was seen in 46% (6/13) of FESS alone, 17% (1/6) with FESS with trephination, 0% (0/9) with FESS with cranialization, and 33% (1/3) with just cranialization alone. CONCLUSIONS: Pott's Puffy tumor patients were younger and predominately male when compared to the control patients. No prior allergy diagnosis, previous trauma history, medication allergy to penicillin class or cephalosporin class, and lower body mass index are risk factors for PPT. There are 2 prognostic factors that predict recurrence of PPT: first operative treatment choice and prior sinus surgery. History of prior sinus surgery tends to increase the recurrence of PPT. The first operative treatment plan is the best shot at definitively treating PPT. Correct management surgically can prevent recurrence of PPT as well as long-term recurrence of chronic rhinosinusitis. With early diagnosis and mild disease, FESS is sufficient to prevent recurrence of PPT but chronic sinusitis may continue to occur if frontal sinus outflow track is not well opened. If considering trephination, a definitive cranialization may be more suited for more advanced disease since our study showed 50% of recurrence of PPT with trephination and FESS along with 17% chronic sinusitis long term. More advanced diseases with higher WBCs and intracranial extension do better with more aggressive surgical management with a cranialization with or without FESS which shows to reduce rates of PPT recurrence significantly.

Antagonistic and cooperative AGO2-PUM interactions in regulating mRNAs.

Approximately 1500 RNA-binding proteins (RBPs) profoundly impact mammalian cellular function by controlling distinct sets of transcripts, often using sequence-specific binding to 3' untranslated regions (UTRs) to regulate mRNA stability and translation. Aside from their individual effects, higher-order combinatorial interactions between RBPs on specific mRNAs have been proposed to underpin the regulatory network. To assess the extent of such co-regulatory control, we took a global experimental approach followed by targeted validation to examine interactions between two well-characterized and highly conserved RBPs, Argonaute2 (AGO2) and Pumilio (PUM1 and PUM2). Transcriptome-wide changes in AGO2-mRNA binding upon PUM knockdown were quantified by CLIP-seq, and the presence of PUM binding on the same 3'UTR corresponded with cooperative and antagonistic effects on AGO2 occupancy. In addition, PUM binding sites that overlap with AGO2 showed differential, weakened binding profiles upon abrogation of AGO2 association, indicative of cooperative interactions. In luciferase reporter validation of candidate 3'UTR sites where AGO2 and PUM colocalized, three sites were identified to host antagonistic interactions, where PUM counteracts miRNA-guided repression. Interestingly, the binding sites for the two proteins are too far for potential antagonism due to steric hindrance, suggesting an alternate mechanism. Our data experimentally confirms the combinatorial regulatory model and indicates that the mostly repressive PUM proteins can change their behavior in a context-dependent manner. Overall, the approach underscores the importance of further elucidation of complex interactions between RBPs and their transcriptome-wide extent.