OBJECTIVES Pancreatic cancer (PC) is a lethal malignancy that lacks specific diagnostic markers. The present study explores the diagnostic potential of the most differentially overexpressed secretory mucin MUC5AC alone and in combination with CA19-9 using multi-center training and validation sets. METHODS The expression of MUC5AC in benign pancreatic pathologies, PC precursor lesions, primary PC tissues and metastatic lesions was evaluated by immunohistochemistry. Circulating MUC5AC levels were measured using sandwich ELISA assay developed in-house, and CA19-9 was measured using radioimmunoassay. A combined training set (n =346) was used to evaluate the diagnostic (n =241) and predictive (n =105, total samples 201 from pre- and post-surgical and chemotherapy set) significance of MUC5AC. Results were further validated with a pre-defined cut-off value using independent sets from the Mayo Clinic (n =94) and the University of Pittsburgh Medical Center (n =321). RESULTS Tissue expression analyses indicated the de novo expression of MUC5AC in pancreatic intraepithelial precursor lesions 1A (PanIN1A); the expression was maintained through all stages of progression to invasive adenocarcinoma. The median circulating MUC5AC levels in patients with resectable early-stage PC (EPC) (stage 1/2; 67.2 ng/ml, IQR: 23.9–382.1) and unresectable late-stage PC (LPC) (stage 3/4; 389.7 ng/ml, IQR: 87.7–948.6) were significantly higher compared with (P-value ≤0.0001) benign controls (BC) (7.2 ng/ml, IQR: 0.4–26.5) and (P-value ≤0.0001) chronic pancreatitis (CP) controls (8.4 ng/ml, IQR: 1.5–19.2). In the diagnostic training set (n =241), MUC5AC efficiently differentiated EPC from healthy controls (HC) (83%/80% sensitive (SN)/specific (SP)), BC (67%/87% SN/SP), and CP (83%/77% SN/SP). Independent validation sets from the Mayo Clinic and UPMC confirmed the diagnostic potential of MUC5AC to differentiate EPC from BC (68%/73%; 65%/83%) and CP (68%/79%; 65%/72%). Furthermore, MUC5AC and CA19-9 combination significantly improved (p-value < 0.001) the diagnostic accuracy for differentiating resectable cases from controls. CONCLUSIONS MUC5AC is a valuable diagnostic biomarker, either alone or in combination with CA19-9, to differentiate PC from CP and benign controls.

Background In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR‐Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR‐Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence‐based findings and recommendation from the full document. Methods ICAR‐Allergic Rhinitis 2023 employed established evidence‐based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results ICAR‐Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion The ICAR‐Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Background Osteoma of the paranasal sinuses are benign bony masses most commonly found in the frontal sinus. In the past, due to the anatomical complexity of the frontal sinus, these often required an open approach, but with the invention of angled tools and endoscopes, many rhinologists are now attempting endoscopic or combined resections. No large systematic reviews currently exist that describe the surgical management of frontal sinus osteoma. Objective To perform a systematic review detailing the surgical resection of frontal sinus osteoma. Review Methods: A systematic literature review was performed using PubMed, Embase, and Ovid databases. Data extracted included demographics, clinical presentation, radiologic, histologic findings, surgical approach, and recurrence. Results A total of 32 studies, with 477 surgically resected tumors, were included in the analysis. Sex data were available for 179 patients (M:F, 93:86), with a mean age of 43.2 years. All resected tumors presented symptomatically: facial pain/headache (80.2%), recurrent sinusitis (30.5%), mucocele (4.3%), cosmetic deformity other than proptosis (12.8%), and proptosis (5.5%). Transnasal endoscopic surgery alone was the most common surgical approach utilized (44.9%), followed by open osteoplastic flaps (36.9%) and endoscopic assisted (18.2%). Osteoma with anterior (79%) and posterior (73%) attachments were treated statistically more often with endoscopic approach compared with floor (42%) and extrasinus (50%) attachment ( P < .0005). There was no statistical difference in approach to masses that crossed the sagittal plane extending from the lamina papyracea (63% endoscopic, 29% endoscopic assisted, 8% open, P = .21). Mean follow-up was 29.7 months, with recurrence or persistent residual disease occurring in 12 patients. Conclusion Despite the increasing use of endoscopic alone procedures for expanding indications, patients may still require an open or endoscopic assisted approach for complete removal.

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Background Studies have not yet examined the trends and risk factors of biphasic and recurrent anaphylaxis in the United States using International Classification of Diseases, tenth revision (ICD‐10) CM codes. The goal of this study is to examine the trends of biphasic and recurrent anaphylaxis in all patient care settings (inpatient, outpatient, emergency department, and observation). Methods We used the Clinformatics database from 2015 to 2017. Our main outcome measure was recurrent anaphylactic events occurring within 1 year after the initial event. We used Cox proportional hazards modeling to assess the factors associated with recurrent anaphylaxis and the Kaplan‐Meier method to estimate time to recurrence. Results There were a total of 19,039 patients with incident anaphylaxis in 2016 and, of these, 2017 had a recurrent anaphylaxis event in the 12‐month period after the index date (10.6%). The most common trigger for recurrent anaphylaxis is venom followed by food allergens. Pediatric patients aged <18 years were more likely to develop recurrent anaphylaxis compared with patients aged 18 to 64 years (hazard ratio [HR], 1.53). Patients with allergic rhinitis and asthma were more likely to develop recurrent anaphylaxis compared to those without these comorbidities (HR, 1.15 and 1.27, respectively). Conclusion This is the first national study using ICD‐10 CM codes looking at rates of biphasic and recurrent anaphylaxis in all patient care settings. Recurrent anaphylaxis is more common in the first 3 days after the initial event, in younger patients (<18 years), and in patients with allergic rhinitis and/or asthma. Physicians need to prescribe epinephrine auto‐injectors and educate their patients about the risk of recurrence.