Importance of Sinonasal Evaluation Before Transplantation: Systematic Review With Meta-Analysis and Proposal of a Screening Protocol.

OBJECTIVES: The immunocompromised status in transplant recipients promotes the development and exacerbation of rhinosinusitis. However, there are no formal guidelines on pretransplant sinonasal evaluations. Here, we aimed to identify the prevalence and mortality rates of rhinosinusitis in the transplant population and to provide an evidence-based pretransplant screening protocol. MATERIALS AND METHODS: For our meta-analysis and systematic review of available literature, we performed an online search on PubMed, Scopus, and Google Scholar. We included 27 articles for review, which included 22 articles for meta-analysis. We assessed the risk of bias on outcome by using the GRADE system. Primary outcome measures were pretransplant prevalence of rhinosinusitis and overall mortality rates. RESULTS: The prevalence of pretransplant rhinosinusitis in hematopoietic stem cell transplant recipients (22.2%) was significantly higher than the prevalence in solid-organ transplant recipients (3.9%) (relative risk 4.9; 95% CI, 4.2-5.6; P < .01). We found no significant difference in overall mortality between transplant recipients with or without rhinosinusitis. However, hematopoietic stem cell transplant recipients with pretransplant rhinosinusitis showed significantly higher risk of overall mortality (relative risk 2.8; 95% CI, 2.1-3.9; P < .05) compared with solid-organ transplant recipients. CONCLUSIONS: Our research assessed the need for a clinical pretransplant sinonasal assessment in all transplant recipients and advised for routine paranasal sinus computed tomography before hematopoietic stem cell transplant, due to the higher prevalence of rhinosinusitis and risk of mortality in this group. We also presented a proposed screening protocol on pretransplant sinonasal evaluation.

Clinical predictors of revision surgery for chronic rhinosinusitis with nasal polyposis within 5-year follow-up.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) remains a difficult-to-cure disease. The aim of this study was to determine the potential long-term predictors of revision sinus surgery for CRSwNP. METHODS: Prospectively gathered patients with bilateral CRSwNP who received primary endoscopic sinus surgery were enrolled. Clinical variables, including the preoperative Lund-Mackay score (LMS), were collected to clarify possible risk factors for revision surgery within a 5-year follow-up. The symptomatic burden was measured using a 10-cm visual analog scale (VAS) before and 1 year after surgery. Further survival analysis was performed to present the revision-free survival in Kaplan-Meier plotting. RESULTS: Eighty four qualified patients were identified and all of them experienced significant improvement in VAS after primary surgery. The 5-year revision rate was 19.05%, and the mean time of revision surgery was 25.31 ± 17.11 months postoperatively. Nasal allergy (OR = 9.287; p = 0.011) and LMS (OR = 1.29; p = 0.06) were found to be the independent risk factors for revision surgery. The discriminatory power of LMS for revision surgery was acceptable (AUC = 0.79) with the best cutoff point located at LMS > 13.5. Patients with both nasal allergy and LMS≧14 had only half of revision-free survival in comparison to overall survival (38.1% vs. 80.95%, p < 0.001). CONCLUSIONS: In patients with CRSwNP who have concurrent nasal allergy and higher preoperative LMS may indicate an advanced disease status and eventually be in a high risk of revision surgery after a long-term follow-up. An outcome-based staging system will be helpful in the future to improve the prognosis for CRSwNP.

Chronic Rhinosinusitis and Allergy: Increased Allergen Sensitization Versus Real Allergic Rhinitis Multimorbidity: a Systematic Review.

PURPOSE OF REVIEW: The objective of this article is to provide a recent update of the association between allergic inflammation and chronic rhinosinusitis. The systematic approach of this review article critically evaluates the literature published over the past few years and summarizes the specific pathophysiologic pathway of chronic sinonasal inflammation that has been postulated. RECENT FINDINGS: From a systematic search of the Ovid Medline and Embase, 11 studies were included in a qualitative analysis of the association between systemic allergy and chronic rhinosinusitis (CRS). Of the 11 studies, four showed an association, three were inconclusive, and four did not show any association. From the systematic search, 50 studies suggested four possible pathophysiologic pathways that may explain the association of allergic inflammation and CRS, namely, (1) staphylococcal enterotoxin, (2) the innate immunity pathway, (3) mast cell-associated inflammation, and (4) dysbiosis of microbiota. The association of systematic allergy and CRS remains inconclusive. The recent advances in the study of the pathophysiologic pathway of CRS may lead to the possibility of a targeted treatment option for CRS.

Treatment outcomes in acute invasive fungal rhinosinusitis extending to the extrasinonasal area.

Acute invasive fungal rhinosinusitis (AIFRS) can spread beyond the sinonasal cavity. It is necessary to analyze the association between the specific site involved in the extrasinonasal area and the survival rate to predict patient prognosis. We investigated 50 patients who had extrasinonasal lesions on preoperative gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scan and underwent wide surgical resection of AIFRS. The specific sites with loss of contrast enhancement (LoCE) on Gd-enhanced MRI were analyzed for AIFRS-specific survival rate. The most common underlying disease was diabetes mellitus followed by hematological malignancy. The most common symptoms were headache and facial pain. Seven patients (14.0%) expired because of AIFRS progression. Poor prognosis was independently associated with LoCE at the skull base on preoperative MRI (HR = 35.846, P = 0.004). In patients with AIFRS extending to the extrasinonasal area, LoCE at the skull base was an independent poor prognostic factor.

Factors associated with all-cause mortality in pediatric invasive fungal rhinosinusitis.

INTRODUCTION: Pediatric invasive fungal rhinosinusitis (PIFR) is a potentially lethal infection seen in immunocompromised pediatric patients. Even with timely treatments, mortality ranges between 18 and 80% of the cases. OBJECTIVE: To analyze the factors associated with all-cause mortality in pediatric patients with acute invasive fungal rhinosinusitis. SETTING: Tertiary pediatric referral center. RESULTS: A total of 18 patients were included, 12 male and 6 female. The average age at diagnosis was 8.7 years (range 4 months-17 years), with 56% overall mortality and 44% survival after 60 months. The most common cause of immunosuppression was acute lymphoblastic leukemia. The only factor found affecting mortality was a time between diagnosis and surgery greater than 7 days. CONCLUSION: PIFR is an aggressive entity with high mortality. An appropriate diagnosis with an opportune surgical debridement followed by systemic antifungal therapy is essential to improve survival. Delay in surgical treatment is associated with higher mortality.

Impact of early detection of acute invasive fungal rhinosinusitis in immunocompromised patients.

BACKGROUND: Early diagnosis of acute invasive fungal rhinosinusitis (AIFRS) is vital to improving outcomes in immunocompromised patients. This study evaluated the impact of a systematic protocol with nasal endoscopy and biopsies to early detect AIFRS in immunocompromised patients. Additionally, we compared the accuracy of frozen-section biopsy and culture with formalin-fixed paraffin-embedded (FFPE) biopsy. METHODS: Retrospective cohort in a Tertiary Referral Hospital. Patients with the suspected diagnosis of AIFRS were evaluated following a standardized protocol, including serial nasal endoscopies and biopsies when necessary. The sensitivity and specificity of frozen-section biopsy and culture were also compared with FFPE. RESULTS: The mortality rate related to AIFRS of this standardized cohort (13/43) was 30.2%. Better outcomes were observed in patients with disease limited to the turbinates and in those with higher peripheral neutrophils count. Frozen-section biopsy positivity correlated with FFPE findings for fungi detection (p-value < 0.0001), with a sensitivity of 90.6%, specificity of 72.7%, and accuracy of 86.0%. CONCLUSION: Implementation of this standardized protocol was related to a considerably low mortality rate among patients with suspected AIFRS at our Institution. Frozen-section biopsy revealed high accuracy to diagnose AIFRS. The current protocol including frozen-tissue biopsy improved the evaluation and survival rates of immunocompromised patients with presumed AIFRS.

Association of Chronic Rhinosinusitis With Depression and Anxiety in a Nationwide Insurance Population.

Importance: Chronic rhinosinusitis (CRS) is associated with a decreased quality of life, affecting physical and emotional aspects of daily function, the latter of which could manifest as depression and anxiety. Objective: To evaluate the risk of depression and anxiety in CRS, depending on the CRS phenotype (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]). Design, Setting, and Participants: This retrospective nationwide cohort study used population-based insurance data (consisting of data from approximately 1 million patients). The study population included 16 224 patients with CRS and 32 448 individuals without CRS, with propensity score matching between groups according to sociodemographic factors and enrollment year. Data were collected from January 1, 2002, through December 31, 2013, and analyzed from July 1 through November 15, 2018. Main Outcomes and Measures: Survival analysis, the log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of depression and anxiety for each group. Results: Among the 48 672 individuals included in the study population (58.8% female), the overall incidence of depression during the 11-year follow-up was 1.51-fold higher in the CRS group than in the non-CRS group (24.2 vs 16.0 per 1000 person-years; adjusted HR, 1.54; 95% CI, 1.48-1.61). The incidence of anxiety was also higher in the CRS group than in the comparison group (42.2 vs 27.8 per 1000 person-years; adjusted HR, 1.57; 95% CI, 1.52-1.62). Moreover, the adjusted HRs of developing depression (CRSsNP, 1.61 [95% CI, 1.54-1.69]; CRSwNP, 1.41 [95% CI, 1.32-1.50]) and anxiety (CRSsNP, 1.63 [95% CI, 1.57-1.69]; CRSwNP, 1.45 [95% CI, 1.38-1.52]) were greater in patients with CRSsNP than in those with CRSwNP. Conclusions and Relevance: This observational study suggests that CRS is associated with an increased incidence of depression and anxiety. Specifically, findings from this study found that patients without nasal polyps showed a higher risk of developing depression and anxiety than those with nasal polyps.

Unsupervised cluster analysis of chronic rhinosinusitis with nasal polyp using routinely available clinical markers and its implication in treatment outcomes.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multidimensional disease. In this study, we performed an unsupervised cluster analysis of CRSwNP using routinely available clinical markers. METHODS: We conducted a retrospective review of patients treated with endoscopic sinus surgery due to medically intractable bilateral CRSwNP from 2009 to 2017. Unsupervised cluster analysis was performed using a patient's clinical features, including age, peripheral blood eosinophil, tissue eosinophilia, Lund-Mackay computed tomography (CT) scores, ratio of the CT scores for the ethmoid sinus and maxillary sinus (E/M ratio), and comorbid asthma. Tree analysis was performed to develop a clustering algorithm. Kaplan-Meier survival analysis was performed to determine the revision surgery-free probability corresponding to each cluster. RESULTS: Data were available on 375 patients. Patients were categorized into 6 clusters comprising 2 asthmatic clusters and 4 non-asthmatic clusters. The labels for the 2 asthmatic clusters were: asthmatic non-eosinophilic polyp (cluster A1) and asthmatic eosinophilic polyp (cluster A2). The labels for the 4 non-asthmatic clusters were: non-eosinophilic polyp with older age (cluster NA1); non-eosinophilic pol'yp with younger age (cluster NA2); eosinophilic polyp with lower E/M ratio (cluster NA3); and eosinophilic polyp with higher E/M ratio (cluster NA4). The 4-year revision-free rates were 100% (cluster NA1), 80.3% (NA2), 98.0% (NA3), 66.7% (NA4), 100% (A1), and 66.7% (A2). The clusters showed statistically significant differences in terms of 4-year revision-free rates (log-rank p < 0.05). CONCLUSION: Cluster analysis identified 2 asthmatic clusters and 4 non-asthmatic clusters in CRSwNP. Each cluster corresponded to a different clinical outcome.

Inpatient Mortality After Endoscopic Sinus Surgery for Invasive Fungal Rhinosinusitis.

OBJECTIVES:: Invasive fungal rhinosinusitis is a rare, life-threatening condition that affects the paranasal sinuses. The standard of care after diagnosis includes surgical debridement and aggressive medical management. Despite treatment, mortality remains unacceptably high. Most data are derived from small cohort experiences, with limited identification of mortality risk factors in the acute setting. The authors used a large national database to better understand clinical factors associated with inpatient mortality for this challenging condition. METHODS:: Using the 2000-2014 National (Nationwide) Inpatient Sample database, the authors identified 979 adult patients with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code of mucormycosis or aspergillosis and a procedure code of sinus surgery. Multivariate imputation by chained equation was performed to account for missing data, followed by multivariate logistic regression to identify predictors of inpatient mortality. RESULTS:: In total, 979 adult patients were identified, with a median age of 57 years. The inpatient mortality rate was 15.8%. The most prevalent comorbidity was hematologic disorders (42.9%). Mucormycosis versus aspergillosis was associated with increased odds of inpatient mortality (odds ratio, 2.95; 95% confidence interval, 2.00-4.34; P < .001). The odds of inpatient mortality were significantly increased between patients with hematologic disorders and those without (odds ratio, 1.92; 95% confidence interval, 1.08-3.39; P = .024). Diabetes (odds ratio, 0.53; 95% confidence interval, 0.34 - 0.80; P = .003) was associated with the lowest odds of inpatient mortality. CONCLUSIONS:: This represents the first population-based study evaluating the factors associated with inpatient mortality. These findings support prior observations demonstrating that the underlying immune dysfunction and type of fungal infection are important predictors of early mortality.