Donaldson, Angela M.

Abstract Objective Rituximab causes B‐cell depletion and hypogammaglobulinemia, increasing risk for infections. This study aims to determine the incidence of chronic rhinosinusitis (CRS) in patients following rituximab therapy. Study Design Retrospective cohort study using chart review of patients prescribed rituximab between January 2019 and January 2025. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Patients with documented rituximab use were included; those with pre‐existing CRS were excluded. Demographic and clinical data—including timing and duration of rituximab therapy, CRS diagnosis, comorbidities (asthma, allergic rhinitis, GERD), and need for sinus surgery—were collected. Descriptive statistics summarized patient characteristics. Group comparisons were performed using t ‐tests, Mann‐Whitney U , and chi‐square tests. Analyses were conducted using SPSS v28. Results Among 17,851 patients prescribed rituximab (median age 64.0 years, M:F ratio 1.1:1), 1105 (6.2%) developed CRS, with an annual incidence of 1.03% (1032 cases per 100,000 person‐years). The median duration of rituximab therapy for those diagnosed with CRS was 5.9 months (IQR, 0.5‐42.6). Most CRS cases occurred after rituximab discontinuation (62.7%, n = 693) compared to during active treatment (37.3%, n = 412). The median delay between rituximab discontinuation and CRS diagnosis was 17.0 months (IQR, 4.3‐41.7). Conclusions This study demonstrates an annual incidence of 1.03% for CRS diagnoses following rituximab. While prior studies report varying CRS incidences in the general population (0.25%‐0.73%), our findings suggest increased risk among rituximab users. Most CRS diagnoses occurred after rituximab discontinuation, emphasizing the need for a comprehensive medication history review during CRS evaluation.

Abstract Objective To examine the impact of immunosuppressive regimens on chronic rhinosinusitis (CRS) development in kidney and liver transplant recipients. Study Design Retrospective cohort study. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Patients who underwent kidney or liver transplantation between November 1, 2021, and November 1, 2022, were included. Patients with documented sinonasal complaints before transplantation were excluded. Diagnoses were based on ICD‐10 codes assigned by board‐certified otolaryngologists, with follow‐up extending through November 2024. Demographic data, relevant comorbidities, CRS diagnoses, and immunosuppressive regimens were collected. Results In total, 1459 transplant recipients (986 kidney, 473 liver) with a mean age of 55.1 years and M:F ratio of 1.5:1 were included. Kidney recipients who received anti‐thymocyte globulin (ATG, Thymoglobulin®) for immunosuppressive induction had a greater risk of CRS compared to those who did not (odds ratio [OR] = 3.0, 95% CI [1.3, 6.9], P = .005). Among liver recipients, patients on cyclosporine, mycophenolate mofetil (MMF), and corticosteroids had a greater risk of CRS compared to those on tacrolimus‐based regimens (OR = 6.0, 95% CI [1.5, 24.1], P = .027). Cyclosporine use was also associated with an increased rate of endoscopic sinus surgery (ESS) compared to tacrolimus (4.2% vs 0.3%, P = .015). Conclusion Tacrolimus‐based regimens are associated with significantly decreased rates of CRS compared to cyclosporine, suggesting that immunosuppressive choice is a modifiable risk factor for sinonasal morbidity in this population.

Abstract Objective To estimate the incidence of de novo chronic rhinosinusitis and identify associated risk factors in kidney and liver transplant recipients without pre‐existing sinonasal complaints. Study design Retrospective cohort study. Setting Multisite study across Mayo Clinic Enterprise locations in Arizona, Florida, Minnesota, and Wisconsin. Methods Records of all patients who underwent kidney or liver transplantation between November 1, 2021, and November 1, 2022 were reviewed. Patients with documented sinonasal complaints prior to transplantation were excluded. Diagnoses were based on ICD‐10 codes assigned by board‐certified otolaryngologists, with follow‐up extending through November 2024. Demographic and clinical variables were collected, and multivariable logistic regression was used to identify predictors of de novo chronic rhinosinusitis. Results Among 1459 transplant recipients (mean age 55.1 years, 59.8% male), the cumulative 2‐year incidence of de novo chronic rhinosinusitis was 2.4% (24/986) in kidney and 2.3% (11/473) in liver transplant recipients ( P = .89). The overall incidence rate was 12.0 cases per 1000 person‐years, exceeding general population estimates. Transplant rejection (OR 3.2, 95% CI 2.5‐3.9, P < .001) and additional organ transplantation (OR 5.0, 95% CI 3.4‐6.5, P = .041) were independently associated with chronic rhinosinusitis development. Conclusion Kidney and liver transplant recipients experience a higher incidence of de novo chronic rhinosinusitis compared to the general population. Transplant rejection and additional organ transplantation significantly increase this risk. Early recognition and management of chronic rhinosinusitis in this population may support improved postoperative outcomes.

Importance Acute invasive fungal rhinosinusitis (AIFRS) is a rapidly progressive and potentially life-threatening infection that predominantly affects immunocompromised patients. Recent advances in diagnostic imaging, antifungal therapy, and surgical techniques may have altered its incidence, morbidity, and mortality. Objective To evaluate temporal trends in the pooled proportion, morbidity, and mortality of AIFRS in immunocompromised patients and assess the association of diagnostic and therapeutic advances. Data Sources Systematic searches of Ovid MEDLINE, Ovid Embase, PubMed, Scopus, Web of Science, Cochrane, and Google Scholar from 1977 through October 20, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study Selection Prospective, retrospective, and cross-sectional studies and case series reporting pooled proportion, morbidity, or mortality of AIFRS in immunocompromised patients were included. Non-English articles, reviews, editorials, and studies with fewer than 10 patients were excluded. Data Extraction and Synthesis Two independent reviewers extracted data using standardized templates; disagreements were resolved by consensus. Risk of bias was assessed using the Newcastle-Ottawa Scale and Murad tool for case series. Random-effects meta-analysis generated pooled proportion, morbidity, and mortality rates with 95% CIs. Heterogeneity was quantified using I 2 statistics. Meta-regression and sensitivity analyses evaluated temporal trends and study-level effects. Main Outcomes and Measures Pooled proportion, morbidity, and mortality rates of AIFRS stratified by publication period (1983-2012 vs 2013-2025). Results A total of 205 studies comprising 48 437 immunocompromised patients (median [range] age, 49.4 [5.2-68.8] years), including 10 311 (21.3%) with AIFRS, were analyzed. The pooled proportion was 11.8% (95% CI, 7.9%-17.2%), rising to 16.6% (95% CI, 8.7%-29.2%) in studies from 2013 to 2025. Overall mortality was 31.2% (95% CI, 28.3%-34.3%), declining from 41.9% (95% CI, 35.0%-49.1%) before 2013 to 28.2% (95% CI, 25.1%-31.4%) after 2013. Morbidity was 37.0% (95% CI, 32.9%-41.4%), with similar rates across periods (39.3% before 2013 vs 36.4% after 2013). The most common complications were vision loss, exophthalmos/proptosis, and orbital exenteration. Conclusions and Relevance This systematic review and meta-analysis suggests that the pooled proportion of AIFRS among immunocompromised patients has increased while mortality has declined, reflecting advances in diagnostic and therapeutic approaches. Early detection and aggressive management remain critical to improving outcomes.

Background A substantial proportion of patients with chronic rhinosinusitis (CRS) remain partly controlled or uncontrolled despite endoscopic sinus surgery (ESS) and maximal medical therapy. For these difficult-to-treat cases, topical antibiotic irrigations have been proposed as an adjunctive therapy, particularly when delivered via large-volume, low-pressure systems that enhance sinus penetration post-ESS. Evidence on their efficacy and prescribing patterns in this population remains limited. Objective This study aims to evaluate the use and outcomes of topical antibiotic irrigations in patients with difficult-to-treat CRS. Methods A retrospective, multi-site cohort study was conducted across tertiary academic medical centers. Adult patients with persistent CRS symptoms despite bilateral full-house ESS and conventional postoperative medical management were included. Patients with cystic fibrosis or granulomatosis with polyangiitis were excluded. Demographic, clinical, and treatment data were collected. Primary outcomes were infection resolution at 8 weeks and changes in Sino-Nasal Outcome Test-22 (SNOT-22) scores. Results Sixty-seven patients met inclusion criteria. Mupirocin (41.8%), tobramycin (23.9%), and gentamicin (17.9%) were the most commonly prescribed agents. After 8 weeks, 62.7% of patients achieved infection clearance. Among 44 patients with SNOT-22 data, scores improved significantly from 34.8 ± 20.2 to 21.8 ± 14.7 ( P < .001). Improvement in SNOT-22 scores was more pronounced in patients who cleared the infection compared to those who did not. Conclusion Large-volume topical antibiotic irrigations were associated with high infection resolution rates and clinically meaningful SNOT-22 improvements in patients with difficult-to-treat CRS. These findings support their potential utility as an adjunctive therapy in select postsurgical patients and warrant further prospective investigation.

Abstract Objective Recurrent acute rhinosinusitis (RARS) significantly decreases quality of life. Transplant recipients (TR) are particularly vulnerable to rhinologic conditions. There is a lack of guidelines for managing RARS in this population. Our study aims to determine the prevalence of and risk factors for RARS among TR and assess the need for sinus surgery within this group. Study Design Retrospective cohort. Setting Mayo Clinic between 2017 and 2022. Methods A total of 1116 patients met the inclusion criteria and were divided based on the presence or absence of a new incident RARS diagnosis during the posttransplant period and frequency of sinus surgery. Logistic regression (LR) analysis was performed to identify the odds ratio. Results In total, 111/1116 (9.95%) had RARS. Patients with RARS had an increased history of asthma, viral infection, and rheumatoid arthritis (RA) ( P = .003) in the pretransplant period. According to the LR analysis, patients with neutropenia, RA, and mantle cell lymphoma were 1.91, 2.71, and 4.02 times more likely to develop RARS (95% CI: 1.19‐3.05, P = .01), (95% CI: 0.90‐8.14, P = .07), and (95% CI: 1.16‐13.89, P = .02) during the posttransplant period, respectively. In those that developed RARS, only 5.5% failed medical therapy and required surgery. Conclusion This is the first cohort to investigate the incidence of RARS in TR and the predictive factors associated with its development posttransplant. We found that patients with pretransplant comorbidities such as RA, viral infections, hematologic deficiencies, and malignancies were at an increased risk for developing RARS, though this is not linked to an increased necessity for sinus surgery.

AbstractThe American Academy of Otolaryngology–Head and Neck Surgery Foundation has published a supplement to this issue of Otolaryngology–Head and Neck Surgery featuring the updated “Clinical Practice Guideline: Adult Sinusitis”. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 developed recommendations address diagnostic accuracy for adult rhinosinusitis, the appropriate use of ancillary tests to confirm diagnosis and guide management (including radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function), and the judicious use of systemic and topical therapy. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, an immunocompromised state, and ciliary dyskinesia. An updated guideline is needed as a result of new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group.

AbstractThe American Academy of Otolaryngology–Head and Neck Surgery Foundation has published the updated “Clinical Practice Guideline: Adult Sinusitis” as a supplement to this issue of Otolaryngology–Head and Neck Surgery. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 developed recommendations address diagnostic accuracy for adult rhinosinusitis, the appropriate use of ancillary tests to confirm diagnosis and guide management (including radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function), and the judicious use of systemic and topical therapy. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia. An updated guideline is needed as a result of new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group.MethodsThis executive summary describes the guideline developed using the 55‐page protocol published as the American Academy of Otolaryngology–Head and Neck Surgery Foundation's Clinical Practice Guideline Development Manual (3rd edition), which summarizes the methodology for assessments of current data, topic prioritization, development of key action statements, application of value judgements, and related procedures. The guideline update group represented the disciplines of otolaryngology–head and neck surgery, infectious disease, family medicine, allergy and immunology, advanced practice nursing, and a consumer advocate.Differences from Prior GuidelineThis clinical practice guideline is as an update, and replacement, for an earlier guideline published in 2015 by the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO‐HNSF).1 An update was planned for 5 years after the initial publication date and was further necessitated by new primary studies and systematic reviews that might suggest a need for modifying clinically important recommendations.2 Changes in content and methodology from the prior guideline include the following: New evidence from 14 guidelines, 194 systematic reviews, and 133 RCTs. Emphasis on patient education and counseling with new explanatory tables. Expanded action statement profiles to explicitly state quality improvement opportunities, confidence in the evidence, intentional vagueness, and differences of opinion. Enhanced external review process to include public comment and journal peer review. New algorithm to clarify decision making, watchful waiting, action statement relationships. Extension of watchful waiting (without antibiotic therapy) as an initial management strategy to all patients with uncomplicated acute bacterial rhinosinusitis (ABRS) regardless of severity, not just patients with “mild” illness (prior guideline). Clarified the recommended timeline for the diagnosis, conservative management and antibiotic treatment of ABRS. Change in recommendation to first‐line antibiotic therapy for ABRS amoxicillin, with or without clavulanate, from amoxicillin alone (prior guideline). Addition of aspirin exacerbated respiratory disease (AERD) as a chronic condition that modifies management of chronic rhinosinusitis (CRS). Three new key action statements on managing CRS that focus on the use of biologics (recommend against when patients do not have polyps and educate patients about them when they do) and a recommendation against the empiric use of antibiotics for CRS solely as a third‐party requirement for surgery or imaging.