Recreating the microscopic direct access Draf 2a frontal sinusotomy in the endoscopic era and comparison to an angled instrument approach.

PURPOSE: Microscopic Draf 2a frontal sinusotomy relied on direct access. However, the modern-day endoscopic approach is hindered by the anterior-posterior dimensions of the frontal recess. The nasofrontal beak, angled endoscopes, and variable frontal recess anatomy make the surgery challenging. Carolyn's window frontal sinusotomy removes the limitation of anterior-posterior dimensions and is an endoscopic version of the microscopic Draf 2a. This study aims to compare the perioperative outcomes and morbidity from endoscopic direct access Draf 2a compared to angled access Draf 2a. METHODS: Consecutive adult patients (> 18 years) seen at a tertiary referral clinic who underwent Draf 2a frontal sinus surgery using either endoscopic direct access (Carolyn's window) or endoscopic angled instrumentation were included. Patients who underwent Carolyn's window were compared to those with angled Draf 2a frontal sinusotomy. RESULTS: One hundred patients (age 51.96 ± 15.85 years, 48.0% female, follow-up 60.75 ± 17.34 months) were included. 44% of patients used Carolyn's window approach. 100% [95% CI 98.2-100%] of patients achieved successful frontal sinus patency. Both groups were comparable for early morbidities (bleeding, pain, crusting, and adhesions) and late morbidities (retained frontal recess partitions). There were no other morbidities in the early and late postoperative periods. CONCLUSION: The endoscopic direct access Draf 2a, or Carolyn's window, removes the anteroposterior diameter limitation. The frontal sinus patency and early and late surgical morbidities of direct access Draf 2a were comparable with the angled Draf 2a frontal sinusotomy. Surgical modifications, often with drills and bone removal, can be successfully made to enhance access in endoscopic sinus surgery without concern for additional morbidity.

Mucosal brushings for nasal specific IgE to predict house dust mite driven allergic rhinitis.

BACKGROUND: Skin prick testing and serological identification of allergen specific immunoglobulin E (spIgE) are standard tests for allergic rhinitis but can only identify systemic responses. In contrast, nasal allergen challenge (NAC), directly assess localized nasal mucosal reactivity, but is time consuming. Identification of spIgE from nasal brushings (nasal spIgE) is an alternative technique. OBJECTIVE: This study aimed to determine the diagnostic performance of nasal spIgE compared to NAC in order predict house dust mite (HDM) driven AR. METHODS: A diagnostic cross-sectional study involving adult rhinitis patients was performed. Sensitization to HDM allergens (Dermatophagoides pteronyssinus (DP), Dermatophagoides farina (DF) were assessed serologically and/or skin prick test, nasal brushing and NAC. Patients with both positive systemic test and NAC were defined to have HDM driven AR, while patients with a positive systemic test and negative NAC were defined to have non-clinically relevant HDM sensitization. The performance of nasal spIgE to predict positive NAC was determined using the receiver operating curve. The chosen cut-off was then used to predict HDM driven AR among those with positive systemic test. RESULTS: 118 patients (29.42 ± 9.32 years, 61.9% female) were included. Nasal spIgE was predictive of positive NAC (AUC 0.93, 95%CI: 0.88-0.98, p < 0.01). Among those with positive systemic test, the cut-off value of >0.14 kUA/L was able to predict HDM AR from incidental HDM sensitization with 92% sensitivity and 86% specificity. CONCLUSIONS: Nasal spIgE is comparable to NAC. A cut-off value of >0.14 kUA/L identifies HDM-driven AR from incidental sensitization among patients with positive systemic tests for allergy.

Mepolizumab decreases tissue eosinophils while increasing type-2 cytokines in eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis is an often treatment-resistant inflammatory disease mediated by type-2 cytokines, including interleukin (IL)-5. Mepolizumab, a monoclonal antibody drug targeting IL-5, has demonstrated efficacy and safety in inflammatory airway disease, but there is negligible evidence on direct tissue response. The study's aim was to determine the local effect of mepolizumab on inflammatory biomarkers in sinonasal tissue of eosinophilic chronic rhinosinusitis patients. METHODS: Adult patients with eosinophilic chronic rhinosinusitis received 100mg mepolizumab subcutaneously at four-weekly intervals for 24 weeks in this prospective phase 2 clinical trial. Tissue eosinophil counts, eosinophil degranulation (assessed as submucosal eosinophil peroxidase deposition by immunohistochemistry) and cytokine levels (measured in homogenates by immunoassay) were evaluated in ethmoid sinus tissue biopsies collected at baseline and at weeks 4, 8, 16 and 24. RESULTS: Twenty patients (47.7 ± 11.7 years, 50% female) were included. Sinonasal tissue eosinophil counts decreased after 24 weeks of treatment with mepolizumab (101.64 ± 93.80 vs 41.74 ± 53.76 cells per 0.1 mm2 ; p = .035), eosinophil degranulation remained unchanged (5.79 ± 2.08 vs 6.07 ± 1.20, p = .662), and type-2 cytokine levels increased in sinonasal tissue for IL-5 (10.84 ± 18.65 vs 63.98 ± 50.66, p = .001), IL-4 (4.48 ± 3.77 vs 9.38 ± 7.56, p = .004), IL-13 (4.02 ± 2.57 vs 6.46 ± 3.99, p = .024) and GM-CSF (1.51 ± 1.74 vs 4.50 ± 2.97, p = .001). CONCLUSION: Mepolizumab reduced eosinophils in sinonasal tissue, demonstrating that antagonism of IL-5 suppresses eosinophil trafficking. With reduced tissue eosinophils, a local type-2 inflammatory feedback loop may occur. The study exposes mechanistic factors which may explain incomplete treatment response.

Systemic medication requirement in post-surgical patients with eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis (eCRS) is contemporarily managed by surgical creation of a 'neo-sinus' cavity and corticosteroid irrigations. While most patients gain control of their disease with this approach, similar to preventive inhaler therapy in asthma, some patients need systemic therapies. This study aimed to define those patients needing ongoing systemic therapy for eCRS. METHODS: Consecutive adult patients (>18 years) who were seen at a tertiary referral clinic, diagnosed as eCRS and underwent endoscopic sinus surgery were included. Patients were followed up for a minimum of 12 months. All patients had a simple neo- sinus cavity surgically created and used initially a once daily topical corticosteroid irrigation maintenance therapy. Patients who re- quired long term systemic oral corticosteroids and/or biologic therapy were compared to those who remained on topical control. RESULTS: 222 patients with eCRS were assessed (follow-up 2.76 years). Long term systemic therapy was required in 5.4% of pa- tients. Receiver operating curve analysis predicted local treatment failure at an eosinophil count cut-off level 0.455x109/L. Asthma, atopy and aspirin sensitivity also predicted long term systemic therapy. There were no associations with nasal polyposis or revi- sion surgery. Multivariate logistic regression showed elevated blood eosinophil count >0.455 x109/L was 9.27 times more likely to require for systemic medication. CONCLUSION: Pre-operative blood eosinophil count >0.45 x109/L was associated with failure of local therapy following contem- porary management of eCRS. The quantitative value of serum eosinophilia may be a useful predictor of disease progression and those patients in need of systemic therapies, such as biologic agents.

Effect of monoclonal antibody drug therapy on mucosal biomarkers in airway disease: A systematic review.

BACKGROUND: Monoclonal antibody therapies have a growing role in treating refractory airway disease. OBJECTIVE: The review aimed to summarize the response of respiratory mucosa to monoclonal antibody treatments in inflammatory airway conditions. DESIGN: We conducted a systematic review including risk of bias assessment. DATA SOURCES: MEDLINE, EMBASE and PubMed from 1 January 2000 to 16 November 2019 were searched. ELIGIBILITY CRITERIA: Eligible studies assessed the immunological and histological response of airway mucosa to monoclonal antibody therapy compared with baseline or a comparison group in patients with respiratory diseases (asthma, chronic rhinosinusitis and allergic rhinitis). Any prospective interventional studies, including randomized controlled trials (RCTs) and single-arm trials, were eligible. RESULTS: There were 4195 articles screened, and full-text analysis produced n = 11 studies with extractable data. Nine were RCTs, and two were single-arm trials. These studies focused on asthma (n = 9 articles), chronic rhinosinusitis (n = 1) and allergic rhinitis (n = 1). Five monoclonal antibody drugs were assessed (omalizumab, mepolizumab, dupilumab, benralizumab and tralokinumab). Risk of bias was low (n = 6) or unclear (n = 3) in the RCTs and moderate in the single-arm trials. Omalizumab reduced the mucosal concentration of its target, IgE. Dupilumab reduced the concentration of one of its targets, IL-13, but not IL-4. Omalizumab, mepolizumab and benralizumab reduced tissue eosinophil cell density. Dupilumab decreased mucosal eosinophil granule proteins. Tralokinumab did not affect airway mucosa. CONCLUSIONS: Knowledge of the expected biological response of monoclonal antibody therapy on biomarkers in disease tissue provides an important supplement to data about clinical outcomes. An understanding of the biological effect is essential to identify likely responders, reasons for treatment failure and necessary adjustments to monoclonal antibody treatment. Further investigation into the effect of monoclonal antibody therapy on disease mucosa and more precise endotyping are required to move closer to achieving personalized medicine.

Outcomes of pituitary surgery for Cushing's disease: a systematic review and meta-analysis.

PURPOSE: Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease (CD). This review aimed to synthesize the remission and recurrence rates following TSS for CD and identify predictors of these outcomes. METHODS: Medline (1946-) and Embase (1947-) were searched until 23rd January 2019 for original studies. A meta-analysis was performed of remission and recurrence rates. Studies were excluded if patients had prior radiosurgery/radiotherapy, mixed pathologies or interventions without separated data, follow-up not reported or population size < 20. For recurrence rate syntheses, studies with follow-up < 6 months were excluded. RESULTS: The search produced 2663 studies, of which n = 68 were included, involving 5664 patients. Remission rates after primary and revision TSS were 80% [77-82] and 58% [50-66] at last follow-up. After primary TSS, predictors of remission were micro- v macroadenomas (83% v 68%, p < 0.01), imaging-visible adenomas (81% v 69%, p < 0.01), adenomas confirmed on histopathology (87% v 45%, p < 0.01), absence of cavernous sinus invasion (80% v 30%, p < 0.01), postoperative serum cortisol (MSeC) nadir < 2 µg/dL (< 55 nmol/L; 95% v 46%, p < 0.01) and lower preoperative 24-h urine free cortisol (1250 nmol v 1726 nmol, p < 0.01). For revision TSS, predictors of remission were postoperative MSeC nadir < 2 µg/dL (< 55 nmol/L; 100% v 38%, p < 0.01) and operations for recurrence v persistence (80% v 54%, p < 0.01). Recurrence rates after primary and revision TSS were 18% [14-22] and 28% [16-42]. CONCLUSIONS: TSS is most effective in primary microadenomas, visible on preoperative imaging and without CS invasion, lower preoperative 24-h urine free cortisol and postoperative MSeC nadir < 2 µg/dL (< 55 nmol/L).

Turbinate loss from non-inflammatory sinonasal surgery does not correlate with poor sinonasal function.

OBJECTIVE: The impact of turbinate resection on nasal function remains a controversial topic. In surgery for inflammatory sinonasal disease, turbinate resection is often avoided. In contrast, turbinate tissue is routinely sacrificed in endoscopic tumor and skull base surgery to achieve negative margins or gain adequate exposure. Anecdotally, these patients experience good self-reported post-operative nasal function despite extensive turbinate tissue loss. This study investigates the impact of turbinate resection on self-reported sinonasal function following endoscopic tumor or skull base surgery. STUDY DESIGN: Retrospective case series. SETTING: Tertiary Australian Hospitals. SUBJECTS AND METHODS: A retrospective review was performed on consecutive post-surgical patients after management for non-inflammatory sinus disease such as tumor resection or endoscopic skull base reconstruction. Outcome variables assessed included a 6-point Likert score for nasal obstruction, a 13-point Likert score for global nasal function and a 5-question sleep score. The degree of turbinate tissue loss (0-4) was determined by the number of inferior or middle turbinate subtotal resections. Regression analysis was performed, accounting for the effect of relevant demographic variables (smoking; asthma; allergic status; gastroesophageal reflux; malignancy; vestibule mucositis) and treatment variables (subtotal septectomy; Draf III; nasal radiotherapy.) RESULTS: 294 patients (age 52.9 ±â€¯17.6 years, 51.0% female) were assessed. Number of turbinates resected was not associated with poorer nasal obstruction score, global nasal function score or sleep score (OR = 1.77[0.93-3.38], OR = 0.60[0.33-1.12], B = 0.56[-1.58-2.69] respectively). Allergy and Draf3 were found to improve postoperative global nasal function score (OR = 2.07[1.04-4.13], P = 0.04, OR = 3.97[1.08-14.49], P = 0.04, respectively). CONCLUSION: In patients where surgery was performed for non-inflammatory sinus disease, turbinate resection is not correlated with poorer postoperative nasal obstruction, sinonasal function nor sleep quality.

Fungal ball of the maxillary sinus and the risk of persistent sinus dysfunction after simple antrostomy.

BACKGROUND: Maxillary sinus fungal ball is a common cause of unilateral maxillary sinusitis. Fungal balls or mycetomas are primarily treated with surgery to remove the fungus. However, this assumes the pre-fungal ball sinus cavity was normal and post-surgery patients may suffer from mucostasis in the sinus cavity with persistent symptoms. It is proposed that fungal balls are potentially a feature of impaired mucus clearance as they are a pathology in their own right. METHODS: A case series of consecutive patients undergoing antrostomy for maxillary sinus fungal ball was performed. Patient factors including age, gender, smoking status, comorbidities (allergy, asthma, and reflux), disease specific factors including duration of symptoms, microbiology (bacterial co-infection, Gram-positive and/or Gram-negative) and preoperative radiologic findings (extent of sinus development, and neo-osteogenesis/bone thickness) were collected. The primary outcome was sinus function defined by evidence of a normal functioning maxillary sinus, with the absence of mucostasis or pooling, on endoscopic exam at three months, six months and last follow-up. Endoscopic evaluation of inflammation was also collected. RESULTS: 28 patients (age 58.5 ± 15.5 years, 64.3% female) were assessed. Mucostasis was present at three months in 39.3%, at six months in 32.1%, and 17.9% at last follow-up. There was no comorbidity or radiologic finding that was associated with failure to normalize. Those patients with mucostasis had a higher modified Lund-Mackay endoscopic score at last follow-up (5.0 ± 0.7 v 0.2 ± 0.6, p < 0.01). CONCLUSIONS: Long term post-operative mucostasis occurred in 17.9% of patients following an adequate maxillary antrostomy for treatment of a fungal ball. Patients with mucostasis had persistent mucosal inflammation and a greater need for further surgery (modified medial maxillectomy).

Nasal mucosal brushing as a diagnostic method for allergic rhinitis.

Background: Allergen specific immunoglobulin E (spIgE) in the nasal mucosa is a biomarker for local allergic rhinitis. Inferior turbinate tissue biopsy is a sensitive method to detect nasal spIgE but is invasive. Nasal brushing is a relatively noninvasive method to detect nasal spIgE that may be of comparable diagnostic utility. Objective: To assess the performance of nasal brushing to obtain a nasal spIgE sample compared with an inferior turbinate tissue biopsy among patients who underwent turbinate surgery. Methods: A diagnostic cross-sectional study that involved participants who were undergoing turbinate surgery was performed. Nasal brushing, inferior turbinate tissue biopsy, blood collection, and skin-prick test (SPT) were performed perioperatively and tested for house-dust allergens. A receiver operating curve was used to assess the performance of the nasal brushings to obtain nasal spIgE samples compared with the inferior turbinate tissue biopsy. The diagnostic utility of nasal brushings of spIgE compared with serum spIgE testing and SPT was also assessed. Results: A total of 157 patients (41.61 ± 14.83 years; 37.6% women) were included. Nasal brushing was an excellent method to sample for nasal spIgE compared with inferior turbinate tissue biopsy (Area under curve (AUC) 0.87 [95% confidence interval {CI}, 0.81-0.93], p < 0.01). Positive house-dust allergen spIgE results of nasal brushings was defined as > 0.1 kUA/L. Nasal brushings for spIgE sampling was also able to predict the presence of serum spIgE (AUC 0.93 [95% CI, 0.89-0.97], p < 0.01) and SPT (AUC 0.80 [95% CI, 0.72-0.87], p < 0.01). Conclusion: Nasal brushing constituted an easy and relatively noninvasive method to sample nasal epithelium. This sampling technique was comparable with an inferior turbinate tissue biopsy and may be developed as a diagnostic tool for the diagnosis of local allergic rhinitis.

Local specific Immunoglobulin E among patients with nonallergic rhinitis: a systematic review.

BACKGROUND: Allergen specific immunoglobulin can be present in the nasal mucosa of patients with non-allergic rhinitis (NAR). This condition is defined as local allergic rhinitis. However, the reported presence of nasal specific immunoglobulin E (nspIgE) among NAR is variable. The aim of this review was to summarize the studies which reported the presence of nspIgE among patients diagnosed as NAR. METHODS: Embase (1947- ) and Medline (1946-) were searched until 6th June 2017. A search strategy was utilized to identify studies on nspIgE among patients with NAR. The target population was patients with symptoms of rhinitis, but negative systemic allergen sensitization. Studies with original data on detectable nspIgE among the NAR population were included. Meta-analysis of single proportions as a weighted probability %(95%CI) was performed. Heterogeneity was explored amongst studies. RESULTS: A search strategy returned 2286 studies and 21 were included. These studies involved 648 participants with NAR. NspIgE was detected using either; 1. nasal secretions, 2. epithelial mucosa sampling, 3. tissue biopsies or 4. In-situ tests. Metaanalysis was performed on studies with nasal secretions. The weighted proportion of detectable nspIgE in nasal secretions within patients with NAR was 10.2 (7.4-13.4) %. Population definitions partly explained variability. Detection of nspIgE was lower in patients without a history suggestive of allergy compared to those with a positive allergic history (0 (0-3.1) % v 19.8 (14.5-25.6) %, p<0.01). CONCLUSION: NAR with positive allergy history suggests presence of nspIgE. These patients warrant further allergology evaluation to confirm localized nasal allergy, as they benefit from allergy therapy such as immunotherapy.

The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages.

The NLRP3 inflammasome is a multimeric protein complex that controls the production of IL-1ß, a cytokine that influences the development of both innate and adaptive immune responses. Helminth parasites secrete molecules that interact with innate immune cells, modulating their activity to ultimately determine the phenotype of differentiated T cells, thus creating an immune environment that is conducive to sustaining chronic infection. We show that one of these molecules, FhHDM-1, a cathelicidin-like peptide secreted by the helminth parasite, Fasciola hepatica, inhibits the activation of the NLRP3 inflammasome resulting in reduced secretion of IL-1ß by macrophages. FhHDM-1 had no effect on the synthesis of pro-IL-1ß. Rather, the inhibitory effect was associated with the capacity of the peptide to prevent acidification of the endolysosome. The activation of cathepsin B protease by lysosomal destabilization was prevented in FhHDM-1-treated macrophages. By contrast, peptide derivatives of FhHDM-1 that did not alter the lysosomal pH did not inhibit secretion of IL-1ß. We propose a novel immune modulatory strategy used by F. hepatica, whereby secretion of the FhHDM-1 peptide impairs the activation of NLRP3 by lysosomal cathepsin B protease, which prevents the downstream production of IL-1ß and the development of protective T helper 1 type immune responses that are detrimental to parasite survival.-Alvarado, R., To, J., Lund, M. E., Pinar, A., Mansell, A., Robinson, M. W., O'Brien, B. A., Dalton, J. P., Donnelly, S. The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages.

Utility of narrow band imaging in the diagnosis of middle turbinate head edema.

PURPOSE: Middle turbinate head edema has recently been found to have high specificity for diagnosis of inhalant allergy. However, subtle mucosal edema can be difficult to appreciate under white light endoscopy. Narrow band imaging (NBI) has the potential to demonstrate edema by identifying reduced mucosal vascularity and improve sensitivity for the detection of mucosal edema. Narrow band imaging was assessed to determine its utility in objectifying mucosal edema. MEATERIALS AND METHODS: A cross-sectional diagnostic study was performed on patients with edematous mucosa of the middle turbinate head. Under traditional white light endoscopy, areas of edematous mucosa were identified. Using NBI, these areas were compared to areas of normal mucosa on the middle turbinate head. NBI images of these same areas were then converted to grey scale and a vascularity index was created by pixel analysis and brightness in Fiji Image J software (Wisconsin, US). RESULTS: Thirty-three middle turbinates were assessed (age 42.4 ±â€¯12.5, 42.4% female). NBI discriminated between areas identified under white light endoscopy as edematous and normal (158.2 ±â€¯48.4 v 96.9 ±â€¯32.7 p < 0.01). Receiver operating curve (ROC) analysis suggested a threshold of 115 brightness units to define endoscopically visible edematous mucosa with sensitivity 70% and specificity 79% (ROC AUC, p = 0.85). CONCLUSIONS: NBI can differentiate edematous from normal mucosa. The potential for an objective measure of mucosal edema may assist research efforts and may provide a more sensitive tool for subtle mucosal inflammatory changes.

Comparison of Allergen Immunotherapy Alone and in Conjunction With Turbinate Surgery for Nasal Obstruction in Perennial Allergic Rhinitis Patients.

BACKGROUND: Nasal obstruction, triggered by allergic rhinitis, often does not resolve with allergen-specific immunotherapy (AIT) alone, thus inferior turbinate reduction surgery (ITR) may be required. This study aims to investigate the impact of combined treatment on nasal obstruction, as evidence is currently limited. METHODOLOGY/PRINCIPAL: A retrospective cohort study of perennial allergic rhinitis patients experiencing nasal obstruction and undergoing ≥12 months AIT was conducted. Two groups were derived, those undergoing AIT-with or without an ITR. Patient reported nasal obstruction (evaluated with questionnaires) and nasal airway function (Nasal Peak Inspiratory Flow [NPIF] and Nasal Airflow Resistance [NAR]) were monitored. The change from baseline to 12 months post-treatment in each group were compared. RESULTS: A total of 118 patients (33.71 ± 14.43 years, 41.5% female) were recruited, 72% had AIT and 28% AIT&ITR. At baseline, the AIT&ITR group had a higher level of nasal obstruction (>moderate%; 63.6% vs 52.9%, P = .048). Post treatment, AIT&ITR group reported greater reduction in nasal obstruction (>1 category change: 75.8% vs 48.2%, P = .002). Similarly, the AIT&ITR group had greater improvement in nasal function by NPIF (-13.9 ± 110.3 L/minute vs -3.4 ± 78.1 L/minute, P = .049) and NAR (-0.120 ± 0.342 Pa/cm³/second vs -0.093 ± 0.224 Pa/cm³/second, P = .050). CONCLUSIONS: Allergic rhinitis patients, with moderate to severe nasal obstruction, who undergo combined AIT&ITR have greater relief of nasal obstruction and improved airflow analysis compared to AIT alone.

Headache in Patients with Sellar Disease: Clinicomorphological Predictors of Headache and the Outcome of Endoscopic Transsphenoidal Surgery.

Objectives Sellar pathologies are frequently found on imaging performed to investigate headache. However, both headache and incidental sellar lesions are common. Hence, this study prospectively examined headache prevalence, phenotype, and severity in patients with sellar pathologies and the impact of transsphenoidal surgery on headache. Methods Patients undergoing transsphenoidal resection of sellar lesions were consecutively recruited. At baseline, participants were defined as having headache or not and headache phenotype was characterized using validated questionnaires. Headache severity was assessed at baseline and 6 months postoperatively using the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Score (MIDAS). Tumor characteristics were defined using radiological, histological, and endocrine factors. Primary outcomes included baseline headache prevalence and severity and headache severity change at 6 months postoperatively. Correlation between headache and radiological, histological, and endocrine characteristics was also of interest. Results Sixty participants (62% female, 47.1 ± 18.6 years) were recruited. Sixty-three percent possessed baseline headache. HIT-6 scores were higher in patients with primary headache risk factors, including younger age (R 2 = -0.417, p = 0.010), smoking history (63.31 ± 7.93 vs 54.44 ± 9.21, p = 0.0060), and family headache history (68.13 ± 7.01 vs 54.94 ± 9.11, p = 0.0030). Headaches were more common in patients with dural invasion (55.70 ± 12.14 vs 47.18 ± 10.15, p = 0.027) and sphenoid sinus invasion (58.87 ± 8.97 vs 51.29 ± 10.97, p = 0.007). Postoperative severity scores improved more with higher baseline headache severity (HIT-6: R 2 = -0.682, p < 0.001, MIDAS: R 2 = -0.880, p < 0.0010) and dural invasion (MIDAS: -53.00 ± 18.68 vs 12.00 ± 17.54, p = 0.0030). Conclusion Headaches in sellar disease are likely primary disorders triggered or exacerbated by sellar pathology. These may respond to surgery, particularly in patients with severe headache and dural invasion.

A helminth cathelicidin-like protein suppresses antigen processing and presentation in macrophages via inhibition of lysosomal vATPase.

We previously reported the identification of a novel family of immunomodulatory proteins, termed helminth defense molecules (HDMs), that are secreted by medically important trematode parasites. Since HDMs share biochemical, structural, and functional characteristics with mammalian cathelicidin-like host defense peptides (HDPs), we proposed that HDMs modulate the immune response via molecular mimicry of host molecules. In the present study, we report the mechanism by which HDMs influence the function of macrophages. We show that the HDM secreted by Fasciola hepatica (FhHDM-1) binds to macrophage plasma membrane lipid rafts via selective interaction with phospholipids and/or cholesterol before being internalized by endocytosis. Following internalization, FhHDM-1 is rapidly processed by lysosomal cathepsin L to release a short C-terminal peptide (containing a conserved amphipathic helix that is a key to HDM function), which then prevents the acidification of the endolysosomal compartments by inhibiting vacuolar ATPase activity. The resulting endolysosomal alkalization impedes macrophage antigen processing and prevents the transport of peptides to the cell surface in conjunction with MHC class II for presentation to CD4(+) T cells. Thus, we have elucidated a novel mechanism by which helminth pathogens alter innate immune cell function to assist their survival in the host.

Carolyn's Window Approach to Unilateral Frontal Sinus Surgery.

OBJECTIVES: Due to the complexity and variety of the frontal recess and sinus anatomy, traditional Draf 2a frontal sinus surgery is challenging. The thickness of the nasofrontal beak and anterior-posterior dimensions of the frontal recess contribute to this complexity. Carolyn's window technique eliminates the limitation of anterior-posterior depth to facilitate a Draf 2a frontal sinusotomy. The approach is a 0° endoscope technique and provides an excellent view of the frontal sinus and recess. We describe Carolyn's window approach to frontal sinus surgery and the perioperative outcomes. METHODS: Consecutive adult patients in whom Carolyn's window technique was applied for frontal sinus dissection as part of the endoscopic management of both inflammatory and neoplastic disease were assessed. The primary outcome was frontal sinus patency. Secondary outcomes were surgical morbidity, defined as early (<90 days) or late (>90 days). RESULTS: Forty-five patients (49.1 ± 17.9 years, 48.9% Female) were assessed. All patients had successful frontal sinus patency (100% [95CI: 92.1%-100%]). Morbidities were adhesion (4.8%), crusting (2.4%), pain (1.2%), and bleeding (1.2%) in the early postoperative period. There were no other morbidities in the early and late postoperative periods. CONCLUSION: Carolyn's window approach to frontal sinusotomy is a technique that evolves from previously described approaches. Successful frontal sinus patency with very low morbidities is achieved while still working with a 0° endoscope. The "axillectomy" performed simplifies frontal recess surgery by removing the anteroposterior diameter limitation and the dexterity required in angled endoscopy and instrumentation. The inferior-based lateral wall mucosal flap and free mucosal grafting expedite the mucosal healing process. Laryngoscope, 133:2496-2501, 2023.

Prelacrimal Approach to Maxillary Sinus Pathology.

BACKGROUND: Access to the anterior, lateral, inferior, and inferomedial maxillary sinus has been a limitation of the middle meatal antrostomy. Expanded techniques such as the modified medial maxillectomy provide access to many of these areas but require remucosalization, and crusting can occur during the recovery phase. The prelacrimal approach (PLA) offers direct 0° endoscope access to these areas. Additionally, PLA can preserve the nasolacrimal duct and mucosal coverage. OBJECTIVES: We describe the current surgical technique and outcomes of PLA patients. METHODS: Consecutive adult patients with pathology addressed by PLA to the maxillary sinus were assessed. The primary outcome was the restoration of the lateral wall, and the secondary outcomes were early (< 90 days) and late morbidity (> 90 days). RESULTS: Forty patients (52.8 ± 17 years, 62.5% female) were assessed. All patients had successful restoration of the lateral nasal wall (100% [95CI: 91.2%-100%]). The complications reported were primarily dysesthesia (early 10% and late 2.5%). CONCLUSION: The PLA provides robust access to the anterior, lateral, inferior, and inferomedial maxilla. PLA offers rapid mucosal recovery while preserving the normal physiology and the lacrimal systems with low morbidity.

A Scoping Review of Artificial Intelligence Research in Rhinology.

BACKGROUND: A considerable volume of possible applications of artificial intelligence (AI) in the field of rhinology exists, and research in the area is rapidly evolving. OBJECTIVE: This scoping review aims to provide a brief overview of all current literature on AI in the field of rhinology. Further, it aims to highlight gaps in the literature for future rhinology researchers. METHODS: OVID MEDLINE (1946-2022) and EMBASE (1974-2022) were searched from January 1, 2017 until May 14, 2022 to identify all relevant articles. The Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist was used to guide the review. RESULTS: A total of 2420 results were identified of which 62 met the eligibility criteria. A further 17 articles were included through bibliography searching, for a total of 79 articles on AI in rhinology. Each year resulted in an increase in the number of publications, from 3 articles published in 2017 to 31 articles published in 2021. Articles were produced by authors from 22 countries with a relative majority coming from the USA (19%), China (19%), and South Korea (13%). Articles were placed into 1 of 5 categories: phenotyping/endotyping (n = 12), radiological diagnostics (n = 42), prognostication (n = 10), non-radiological diagnostics (n = 7), surgical assessment/planning (n = 8). Diagnostic or prognostic utility of the AI algorithms were rated as excellent (n = 29), very good (n = 25), good (n = 7), sufficient (n = 1), bad (n = 2), or was not reported/not applicable (n = 15). CONCLUSIONS: AI is experiencing an increasingly significant role in rhinology research. Articles are showing high rates of diagnostic accuracy and are being published at an almost exponential rate around the world. Utilizing AI in radiological diagnosis was the most published topic of research, however, AI in rhinology is still in its infancy and there are several topics yet to be thoroughly explored.

Bacterial colonization differences between central compartment atopic disease and eosinophilic chronic rhinosinusitis.

KEY POINTS: Culturable bacterial colonization is similar between type 2 CRS phenotypes Staphylococcus aureus coinfection is similar between eosinophilic CRS and CCAD Patients with CCAD were younger, consistent with current knowledge of the disease.

CCAD or eCRS: Defining Eosinophilic Subpopulations in Chronic Rhinosinusitis.

BACKGROUND: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone. OBJECTIVE: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS. METHODS: A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry. RESULTS: 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (τb = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm2, p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00-6.00] vs 6.00[6.00-6.75], p = 0.015). Other outcomes were similar. CONCLUSIONS: Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations.