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.

Nanoscale CuO charge and morphology control Fusarium suppression and nutrient biofortification in field-grown tomato and watermelon.

Limited data exist on how surface charge and morphology impact the effectiveness of nanoscale copper oxide (CuO) as an agricultural amendment under field conditions. This study investigated the impact of these factors on tomatoes and watermelons following foliar treatment with CuO nanosheets (NS-) or nanospikes (NP+ and NP-) exhibiting positive or negative surface charge. Results showed plant species-dependent benefits. Notably, tomatoes infected with Fusarium oxysporum had significantly reduced disease progression when treated with NS-. Watermelons benefited similarly from NP+. Although disease suppression was significant and trends indicated increased yield, the yield effects weren't statistically significant. However, several nanoscale treatments significantly enhanced the fruit's nutritional value, and this nano-enabled biofortification was a function of particle charge and morphology. Negatively charged nanospikes significantly increased the Fe content of healthy watermelon and tomato (20-28 %) and Ca in healthy tomato (66 %), compared to their positively charged counterpart. Negatively charged nanospikes also outperformed negatively charged nanosheets, leading to significant increases in the content of S and Mg in infected watermelon (37-38 %), Fe in healthy watermelon (58 %), and Ca (42 %) in healthy tomato. These findings highlight the potential of tuning nanoscale CuO chemistry for disease suppression and enhanced food quality under field conditions.

Histopathological Differences in Adult and Elderly Patients With Chronic Rhinosinusitis.

BACKGROUND: Adult and elderly patients with chronic rhinosinusitis (CRS) undergo similar therapeutic management. Few studies have undertaken sinonasal tissue-level comparisons of these groups. This study examines histopathological differences between adults (>18, <65 years) and the elderly (≥65 years) with CRS, with the goal of optimizing medical management. METHODS: In a retrospective cohort analysis, demographic factors, comorbidities, and a structured histopathological report of 13 variables were compared across adult and elderly patients with CRS who underwent functional endoscopic sinus surgery. These cohorts of adult and elderly patients included patients with and without nasal polyps (NP). RESULTS: Three hundred adult (158 aCRSsNP, 142 aCRSwNP) and 77 elderly (38 eCRSsNP, 39 eCRSwNP) patients were analyzed. Mean age of the adult cohort was 44.4 ± 12.4 years, while that of the elderly cohort was 71.9 ± 5.9 years (P < .001). Significantly more adults compared to elderly individuals demonstrated a positive atopic status (79.7% vs 64.0%, P = .004). Elderly patients exhibited higher rates of comorbid diabetes mellitus than adult patients (21.6% vs 10.3%, P = .009). Adults exhibited more tissue eosinophilia (43.4% vs 28.6%, P = .012) and presence of eosinophil aggregates (25.0% vs 14.3%, P = .029) compared to elderly patients, regardless of NP status. Conversely, the elderly demonstrated significantly more fungal elements (11.7% vs 3.0%, P = .004), and trended toward increased overall inflammation (63.6% vs 55.3%, P = .118) and tissue neutrophilia (35.1% vs 27.3%, P = .117), compared to adults. CONCLUSION: Sinonasal tissue of adult and elderly patients with CRS demonstrates clear histopathological differences. Patient comorbidities, in addition to histopathological characterizations, may provide further context for management optimization. LEVEL OF EVIDENCE: 2. SHORT SUMMARY: Sinonasal tissue samples from adult and elderly patients with CRS demonstrate clear histopathological differences. These patient populations also exhibit unique comorbidities. These distinctions have the potential to inform and optimize management of this condition.

Histopathologic Features of Chronic Rhinosinusitis in Diabetic Patients.

OBJECTIVE: To explore how diabetes mellitus impacts chronic rhinosinusitis clinically and on structured histopathology to provide insights on new potential chronic rhinosinusitis endotypes. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic center. METHODS: A retrospective study of chronic rhinosinusitis patients who underwent functional endoscopic sinus surgery from 2015 to 2020 was performed. Structured 13-variable histopathology reports were generated from intraoperative sinonasal specimens. These variables were compared against demographic factors, comorbidities, culture data, and preoperative Lund-Mackay and SNOT-22 scores using logistic regression. RESULTS: There were 411 patients, including 52 diabetics. Diabetes was associated with higher mean body mass index (34.9 vs 29.2; p < .001), age (57.8 vs 48.0; p < .001), and Gram-negative (40.2% vs 22.7%; p < .030) and coagulase-negative Staphylococcus (49.0% vs 28.5%; p = .008) culture rates. Black (23.1% vs 18.7%) and Hispanic (23.1% vs 8.6%) races were more common with diabetes (p = .026). Gender, smoking, polyp status, and Lund-Mackay and SNOT-22 scores did not differ between groups. Diabetics had more fungal elements (13.5% vs 3.3%, p = .018); no other histopathological differences were seen. When controlling for demographic variables and comorbidities, diabetes independently predicted the presence of fungal elements (HR 4.38, p = .018). CONCLUSION: Diabetic chronic rhinosinusitis patients demonstrated increased fungal elements on structured histopathology. Other histopathological features were unaffected by diabetes. These findings may have important implications on the medical and surgical management of diabetic chronic rhinosinusitis patients in which early fungal disease assessment is paramount.

Diversity and Potential Multifunctionality of Archaeal CetZ Tubulin-like Cytoskeletal Proteins.

Tubulin superfamily (TSF) proteins are widespread, and are known for their multifaceted roles as cytoskeletal proteins underpinning many basic cellular functions, including morphogenesis, division, and motility. In eukaryotes, tubulin assembles into microtubules, a major component of the dynamic cytoskeletal network of fibres, whereas the bacterial homolog FtsZ assembles the division ring at midcell. The functions of the lesser-known archaeal TSF proteins are beginning to be identified and show surprising diversity, including homologs of tubulin and FtsZ as well as a third archaea-specific family, CetZ, implicated in the regulation of cell shape and possibly other unknown functions. In this study, we define sequence and structural characteristics of the CetZ family and CetZ1 and CetZ2 subfamilies, identify CetZ groups and diversity amongst archaea, and identify potential functional relationships through analysis of the genomic neighbourhoods of cetZ genes. We identified at least three subfamilies of orthologous CetZ proteins in the archaeal class Halobacteria, including CetZ1 and CetZ2 as well as a novel uncharacterized subfamily. CetZ1 and CetZ2 were correlated to one another as well as to cell shape and motility phenotypes across diverse Halobacteria. Among other known CetZ clusters in orders Archaeoglobales, Methanomicrobiales, Methanosarcinales, and Thermococcales, an additional uncharacterized group from Archaeoglobales and Methanomicrobiales is affiliated strongly with Halobacteria CetZs, suggesting that they originated via horizontal transfer. Subgroups of Halobacteria CetZ2 and Thermococcales CetZ genes were found adjacent to different type IV pili regulons, suggesting potential utilization of CetZs by type IV systems. More broadly conserved cetZ gene neighbourhoods include nucleotide and cofactor biosynthesis (e.g., F420) and predicted cell surface sugar epimerase genes. These findings imply that CetZ subfamilies are involved in multiple functions linked to the cell surface, biosynthesis, and motility.

Histopathologic differences between adult and pediatric patients with chronic rhinosinusitis.

BACKGROUND: Adult and pediatric patients with chronic rhinosinusitis (CRS) may have differing philosophies in therapeutic management. Few studies have examined sinonasal tissue-level comparisons of these groups. This study examines histopathologic differences between children and adults with CRS, with the goal of understanding disease pathogenesis and optimizing medical management for both populations. METHODS: In a retrospective cohort of CRS patients who underwent functional endoscopic sinus surgery (FESS), demographic factors, pertinent comorbidities, and a structured histopathologic report of 13 variables were compared across pediatric and adult CRS patients with and without nasal polyps (pCRSwNP, pCRSsNP, aCRSwNP, aCRSsNP, respectively). RESULTS: A total of 378 adult (181 aCRSsNP, 197 aCRSwNP) and 50 pediatric (28 pCRSsNP, 22 pCRSwNP) patients were analyzed. Significantly more children compared with adults had a comorbid asthma diagnosis (64.5% vs. 37.2%, p = 0.003). Adults with CRS exhibited significantly more tissue neutrophilia (28.9% vs. 12.0%, p = 0.006), basement membrane thickening (70.3% vs. 44.0%, p < 0.001), subepithelial edema (61% vs. 30.0%, p < 0.001), squamous metaplasia (22.0% vs. 4.0%, p < 0.001), and eosinophil aggregates (22.8% vs. 4.0%, p < 0.001) than children with CRS. The majority (66.5%) of adult CRS patients exhibited a lymphoplasmacytic-predominant inflammatory background, whereas the majority (57.8%) of children with CRS exhibited a lymphocyte-predominant inflammatory background. CONCLUSIONS: Sinonasal tissue of adult and pediatric CRS patients demonstrates clear histopathologic differences. Our findings provide insight into differing pathophysiology, which may enable optimization of targeted therapies for patients in each of these unique clinical groups.

Patient safety and quality improvements in parotid surgery.

Parotidectomy is the mainstay treatment for tumors of the parotid gland. In an effort to improve clinical outcomes, several modern surgical techniques and perioperative interventions have been evaluated and refined. This review discusses current and actively debated perioperative interventions aimed at improving patient safety and the quality of parotidectomy. Relevant high-impact literature pertaining to preoperative diagnostic modalities, intraoperative surgical techniques, and postoperative care will be described.

Prognostic Indicators of Survival in Sinonasal Diffuse Large B-Cell Lymphoma: A National Cancer Database Analysis.

OBJECTIVES/HYPOTHESIS: This study offers an update on the epidemiologic and prognostic factors and treatment-specific outcomes in patients diagnosed with sinonasal diffuse large B-cell lymphoma (DLBCL). STUDY DESIGN: Retrospective cohort study. METHODS: National Cancer Database was queried from 2004 to 2016 for patients with sinonasal DLBCL. Univariate Kaplan-Meier and multivariate Cox-regression analyses were performed to evaluate the association of suspected prognostic factors with overall survival (OS). RESULTS: A total of 2,222 patients with sinonasal DLBCL were analyzed. OS was 62% at 5 years and 42% at 10 years. Prognostic factors associated with increased survival included African-American race (HR: 0.48, 95% CI: 0.33-0.70), chemotherapy (HR: 0.30, CI: 0.25-0.35), and radiation (HR: 0.80, CI: 0.69-0.93). Prognostic factors associated with decreased survival included patients with Charlson-Deyo scores of 1 (HR: 1.51, CI: 1.25-1.84), 2 (HR: 2.25, CI: 1.67-3.03), and 3 (HR: 2.36, CI: 1.49-3.74) and patients with Lugano stage III (HR: 1.69, CI: 1.09-2.62) and IV (HR: 1.96, CI: 1.46-2.64) disease. Stage-based split multivariate analysis was performed and revealed chemotherapy was independently associated with increased OS in patients with stage I (HR: 0.24, CI: 0.19-0.30), II (HR: 0.17, CI: 0.11-0.28), and IV (HR: 0.41, CI: 0.26-0.64) disease. Radiotherapy was independently associated with increased OS in patients with stage I disease only (HR: 0.67, CI: 0.55-0.83), while immunotherapy was an independent prognostic factor in patients with stage IV disease only (HR: 0.60, CI: 0.37-0.98). CONCLUSION: This study is the largest to date to analyze the association of demographic features and treatment modalities with OS in patients with sinonasal DLBCL. It is the first to investigate the association of immunotherapy with OS in this population. A combination treatment of immunochemotherapy or radioimmunochemotherapy confers increased survival, particularly in patients with advanced disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1515-1522, 2022.

The possibility of short-term hypothalamic-pituitary-adrenal axis suppression with high-volume, high-dose nasal mometasone irrigation in postsurgical patients with chronic rhinosinusitis.

BACKGROUND: Medically refractory chronic rhinosinusitis (CRS) is often treated with functional endoscopic sinus surgery (FESS) and high-volume steroid nasal irrigation. While budesonide is the most common steroid irrigation for this indication, mometasone has a superior pharmacokinetic profile, which may allow dose escalation. The safety and efficacy of mometasone at higher concentrations than previously used in treating CRS have not been explored. METHODS: Patients were recruited from a tertiary level clinic between June 2018 and December 2019. Inclusion criteria included adults (>18 years); CRS diagnosis; previous FESS; pre-treatment morning cortisol within normal range; minimum of twice daily high-volume sinonasal mometasone irrigations (total dose of 4 mg) for 12 weeks; and post-treatment morning cortisol measured within 2 weeks following the study period. Patients with potential for endogenous or exogenous disruption of the HPA axis were excluded. RESULTS: 14 patients were enrolled in this prospective cohort study. In all but one patient, pre- and post-treatment morning cortisol levels were not significantly different and were within normal limits (6.7-25.4 µg/dL). Following an uninterrupted 12-week treatment course, no evidence of HPA axis suppression was found (P = 0.915). The single patient who was found to have a low (1.3 µg/dL) post-treatment morning serum cortisol level reportedly received an intraarticular steroid shot several days prior to the blood draw. She remained asymptomatic and her rechecked serum cortisol was within normal limits at 12.3 µg/dL. CONCLUSIONS: High-volume 2 mg twice daily sinonasal mometasone irrigations did not cause HPA axis suppression in a representative sample of patients with refractory CRS post-FESS with normal baseline cortisol levels.

Ticks as novel sentinels to monitor environmental levels of per- and polyfluoroalkyl substances (PFAS).

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, ubiquitous pollutants. It is important to continuously monitor the presence of PFAS contamination, utilizing both legacy and new sentinels. In this study, environmental PFAS levels were evaluated using ticks as a sentinel model due to their world-wide distribution, hematophagous nature, and ease of collection and sampling. Hematophagy in discrete blood meals, from a suite of vertebrates, allows ticks to sample dozens of species of consumers and bioaccumulation across communities. Four different species of ticks, across two states (NY, n = 28 in mid-April of 2020 and FL, n = 32 between 2015 and 2020) with two sampling sites in each state were analyzed for the presence of 53 PFAS. The total PFAS concentration in ticks was the lowest at Newburgh (NY), a site that has been undergoing remediation efforts, while the highest total PFAS concentrations were measured in ticks at the Sweetwater site, a wastewater treatment wetland. Detection of PFAS and the potential for variation between tick species and between locations are necessary to establish the utility of ticks as sentinels, in addition to assessing additional environmental factors, such as other wildlife, water, or soil.

Defining the Allergic Endotype of Chronic Rhinosinusitis by Structured Histopathology and Clinical Variables.

BACKGROUND: Atopy has a strong association with chronic rhinosinusitis (CRS). OBJECTIVE: To understand whether patients with atopy and CRS can be defined by markers of tissue histopathology, systemic biomarkers, and clinical factors, which may guide their response to new pharmacologic agents. METHODS: In a retrospective cohort of CRS patients who underwent functional endoscopic sinus surgery, a structured histopathology report consisting of 12 variables, comorbid conditions, preoperative total serum IgE levels, and preoperative modified Lund-Kennedy endoscopic and sinonasal outcome test (SNOT-22) scores were compared between atopic CRS (aCRS) and non-aCRS control patients in a multivariable model. RESULTS: A total of 380 CRS patients were enrolled, 286 of whom had comorbid atopy (aCRS). Compared with non-aCRS, aCRS patients had significantly higher preoperative total SNOT-22 scores (40.45 ± 22.68 vs 29.70 ± 20.68, P = .015) and symptom-specific SNOT-22 scores in all domains except psychological dysfunction. Relative to non-aCRS, aCRS patients had increased tissue eosinophilia (P < .0001), eosinophil aggregates (P < .0001), Charcot-Leyden crystals (P < .04), fibrosis (P < .02), total serum IgE levels (P < .04), polyploid disease (P < .001), and a prevalence of comorbid asthma (P < .0001) and aspirin exacerbated respiratory disease (AERD) (P < .003). Patients with aCRS demonstrated increased tissue eosinophilia compared with non-aCRS patients even after controlling for polypoid disease, asthma, and AERD. CONCLUSION: In the context of CRS, atopy appears to be a specific predictor of CRS severity linked to specific histopathologic variables, including enhanced eosinophilic aggregates. Moving forward, allergic status may be a useful way to identify an atopic endotype of CRS patients. Furthermore, after surgery, patients are often maintained on intranasal corticosteroids. In patients whose disease is unresponsive to steroids, we may look to atopic status to identify another management therapy. Atopic CRS patients, irrespective of polyp and asthmatic status, could be optimal candidates for biologic agents such as T-helper cell, eosinophil, and/or IgE-targeted therapies.

Computational modeling of tau pathology spread reveals patterns of regional vulnerability and the impact of a genetic risk factor.

Neuropathological staging studies have suggested that tau pathology spreads through the brain in Alzheimer's disease (AD) and other tauopathies, but it is unclear how neuroanatomical connections, spatial proximity, and regional vulnerability contribute. In this study, we seed tau pathology in the brains of nontransgenic mice with AD tau and quantify pathology development over 9 months in 134 brain regions. Network modeling of pathology progression shows that diffusion through the connectome is the best predictor of tau pathology patterns. Further, deviations from pure neuroanatomical spread are used to estimate regional vulnerability to tau pathology and identify related gene expression patterns. Last, we show that pathology spread is altered in mice harboring a mutation in leucine-rich repeat kinase 2. While tau pathology spread is still constrained by anatomical connectivity in these mice, it spreads preferentially in a retrograde direction. This study provides a framework for understanding neuropathological progression in tauopathies.

Distinct Histopathologic Features of Complicated Sinusitis.

BACKGROUND: Sinusitis complicated by intracranial or orbital extension can be life-threatening and require emergent intervention. Histologic features of complicated sinusitis have yet to be determined and may have significant implications for understanding pathophysiology. METHODS: A structured histopathology report was utilized to analyze sinus tissue extracted during functional endoscopic sinus surgery (FESS). A total of 13 histopathology variables were compared between patients with complicated sinusitis (CS), CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP). RESULTS: About 24 CS, 149 uncomplicated CRSsNP, and 191 uncomplicated CRSwNP patients were analyzed. Nasal tissue from CS and CRSwNP patients demonstrated similar levels of overall inflammation (66.7% vs. 69.6% with moderate/severe inflammation, P = .466). Relative to CRSsNP, CS patients showed significantly greater overall inflammation (66.7% vs. 41.6%, P = .019). CS patients demonstrated significantly fewer eosinophils per high power field (eos/HPF) and eosinophil aggregates compared to CRSwNP patients (20.8% vs. 70.7% with 5+eos/HPF, P < .0001; 4.2% vs. 33.5%, P < .0001). Relative to CRSsNP patients, CS patients demonstrated enhanced neutrophil infiltration (45.8% vs. 28.0%, P = .011). About 91.7% of CS patients demonstrated a lymphoplasmacytic predominant inflammatory infiltrate, compared to 69.8% of CRSsNP and 62.8% of CRSwNP patients (P < .0001). CONCLUSION: Significant histopathological differences were evident in patients with CS, CRSsNP, and CRSwNP. CS patients did not perfectly fit either a CRSsNP or CRSwNP profile, underscoring the importance of delineating the histopathological features of CS. This study offers insight into the histologic aspects of CS, providing initial evidence that it is an aggressive neutrophilic inflammatory process.

Patients' Perceptions of Resident Surgeon Involvement in Otolaryngology.

OBJECTIVES: To assess patient acceptance of resident involvement in otolaryngologic procedures and to evaluate the impact of a written preoperative educational pamphlet. STUDY DESIGN: Prospective cohort study. METHODS: This is a prospective survey study at a large tertiary care academic center. In addition to standard perioperative instructions and informed consent, 87 out of 183 patients received a pamphlet with information on the role of the otolaryngology resident. RESULTS: Greater than 90% of all patients surveyed recognized that resident physicians are directly involved in delivering care at teaching hospitals and may have assisted in their surgical procedure. Ninety percent of patients receiving educational pamphlets were aware residents may have performed portions of their procedure versus 71% in the control group (P = .001). Ninety-seven percent of patients receiving pamphlets wanted to know how much of their procedure was performed by a resident versus 71% of the control group (P < .001), and patients undergoing single-surgeon procedures were less likely to want to know how much was performed by a resident (P < .05). Ninety-six percent in the pamphlet group agreed that residents improved the quality of their care versus 79% of the control group (P = .001). DISCUSSION: Resident surgeons are well received by the large majority of otolaryngology patients. Structured perioperative information regarding surgical training facilitates an honest and open informed consent discussion between the patient and surgeon and helps to establish a solid foundation of trust. CONCLUSION: Implementation of this practice is simple and inexpensive. It should be considered for any clinical practice with a focus on surgical education. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2448-2454, 2021.

Improved growth and morphological plasticity of Haloferax volcanii.

Some microbes display pleomorphism, showing variable cell shapes in a single culture, whereas others differentiate to adapt to changed environmental conditions. The pleomorphic archaeon Haloferax volcanii commonly forms discoid-shaped ('plate') cells in culture, but may also be present as rods, and can develop into motile rods in soft agar, or longer filaments in certain biofilms. Here we report improvement of H. volcanii growth in both semi-defined and complex media by supplementing with eight trace element micronutrients. With these supplemented media, transient development of plate cells into uniformly shaped rods was clearly observed during the early log phase of growth; cells then reverted to plates for the late log and stationary phases. In media prepared with high-purity water and reagents, without supplemental trace elements, rods and other complex elongated morphologies ('pleomorphic rods') were observed at all growth stages of the culture; the highly elongated cells sometimes displayed a substantial tubule at one or less frequently both poles, as well as unusual tapered and highly curved forms. Polar tubules were observed forming by initial mid-cell narrowing or tubulation, causing a dumbbell-like shape, followed by cell division towards one end. Formation of the uniform early log-phase rods, as well as the pleomorphic rods and tubules were dependent on the function of the tubulin-like cytoskeletal protein, CetZ1. Our results reveal the remarkable morphological plasticity of H. volcanii cells in response to multiple culture conditions, and should facilitate the use of this species in further studies of archaeal biology.

Inter-pathologist Agreement on Structured Histopathology Reporting in Chronic Rhinosinusitis.

BACKGROUND: Structured histopathology reporting is increasingly being utilized in rhinology to characterize endotypes in chronic rhinosinusitis and guide management decisions after sinus surgery. OBJECTIVE: The goal of this investigation is to evaluate inter-observer agreement in structured histopathology reporting. METHODS: Two experienced head and neck pathologists independently compiled structured histopathology reports for tissue samples collected during functional endoscopic sinus surgery. Cohen's standard kappa (κ) coefficients were calculated for each histopathologic variable to assess inter-pathologist agreement. RESULTS: A total of 92 cases were analyzed. Substantial inter-pathologist agreement was reached on tissue eosinophil count (κ = 0.64, P < .001), the presence of eosinophil aggregates (κ = 0.62, P < .001), and the presence of fungal elements (κ = 0.74, P < .001). There was moderate agreement on the degree of inflammation (κ = 0.56, P < .001) and the presence of squamous metaplasia (κ = 0.46, P < .001). There was fair agreement on the presence of neutrophil infiltrates (κ = 0.33, P < .001), the presence of hyperplastic changes (κ = 0.40, P < .001), and the presence of fibrosis (κ = 0.24, P = .022). There was only slight agreement on the degree of subepithelial edema (κ = 0.20, P = .008). The κ coefficients for basement membrane thickening and mucosal ulceration were not statistically significant. CONCLUSION: High inter-pathologist agreement was demonstrated for several salient histopathologic variables, including tissue eosinophil count and the presence of eosinophil aggregates. However, refining the definitions of certain histopathologic variables may improve the reproducibility of structured histopathology reporting.

α-Synuclein modulates tau spreading in mouse brains.

α-Synuclein (α-syn) and tau aggregates are the neuropathological hallmarks of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively, although both pathologies co-occur in patients with these diseases, suggesting possible crosstalk between them. To elucidate the interactions of pathological α-syn and tau, we sought to model these interactions. We show that increased accumulation of tau aggregates occur following simultaneous introduction of α-syn mousepreformed fibrils (mpffs) and AD lysate-derived tau seeds (AD-tau) both in vitro and in vivo. Interestingly, the absence of endogenous mouse α-syn in mice reduces the accumulation and spreading of tau, while the absence of tau did not affect the seeding or spreading capacity of α-syn. These in vivo results are consistent with our in vitro data wherein the presence of tau has no synergistic effects on α-syn. Our results point to the important role of α-syn as a modulator of tau pathology burden and spreading in the brains of AD, PDD, and DLB patients.