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.

Experiencia de 10 años en pacientes operados por rinosinusitis fúngica invasiva aguda / 10-year experience in patients operated for acute invasive fungal rinosinusitis

INTRODUCCIÓN: La rinosinusitis fúngica invasiva aguda (RSFIA) es una enfermedad poco frecuente, de alta mortalidad. Se presenta principalmente en pacientes inmunocomprometidos con múltiples comorbilidades, lo que dificulta su manejo. El objetivo de este trabajo es describir una cohorte de pacientes operados por RSFIA, sus características clínicas y mortalidad, los agentes etiológicos y el rendimiento de los métodos de diagnóstico. MATERIAL Y MÉTODO: Estudio prospectivo no concurrente de pacientes operados por RSFIA entre el 2005 y 2015 en nuestro centro. RESULTADOS: Se incluyeron 32 pacientes, 62,5% (20/32) hombres, con una edad promedio de 39,4 años (16-65 años). La mortalidad global fue del 71,9%, correspondiendo un 46,9% a mortalidad en agudo y un 25% a tardía. Las neoplasias hematológicas fueron la enfermedad de base más frecuente, correspondiendo al 84,4% (27/32) de los casos, seguida de la diabetes mellitus en un 9,4% (3/32). El 62,5% (20/32) de los pacientes presentó neutropenia al diagnóstico, y un 80% (16/20) de ellos, neutropenia febril. El síntoma más frecuente fue la fiebre en un 65,6% (21/32), luego dolor facial o cefalea en un 53,1% (17/32). Se identificó Aspergillus en el 37,5% (12/32), seguido por Rhizopus en el 31,3% (10/32). No se encontró asociación entre las variables estudiadas y un mayor riesgo de mortalidad. CONCLUSIONES: La RSFIA es una enfermedad agresiva con una alta mortalidad, siendo fundamental el diagnóstico oportuno. Es necesario optimizar los criterios de sospecha para un diagnóstico precoz que permita mejorar el pronóstico

INTRODUCTION: Acute invasive fungal rhinosinusitis (AIFRS) is rare but has high mortality. It is more frequent in immunocompromised patients with multiple comorbidities, which make their management more difficult. The aim of this study is to describe a cohort of patients operated due to AIFRS, their clinical characteristics, mortality, aetiological agent and efficacy of diagnostic tests. MATERIAL AND METHOD: Non-concurrent prospective study of patients with AIFRS who were operated between 2005 and 2015 in our centre. RESULTS: Thirty-two patients were included, 62.5% (20/32) men, with an average age of 39.4 years (16-65 years). Overall mortality was 71.9%; acute mortality 46.9% and late mortality 25%. Haematological malignancies were the most common underlying disease, present in 84.4% (27/32) of cases, followed by diabetes mellitus in 9.4% (3/32). On diagnosis, 62.5% (20/32) of patients were neutropenic, 80% (16/20) of them with febrile neutropenia. Fever was the most frequent symptom, present in 65.6% (21/32) of patients, followed by facial pain or headache in 53.1% (17/32). Aspergillus was identified in 37.5% (12/32) of cases and Rhizopus in 31.3% (10/32). There was no association between the analysed variables and increased risk of mortality. CONCLUSIONS: AIFRS is an aggressive disease with a high mortality rate, therefore a timely diagnosis is fundamental. It is necessary to optimise suspicion criteria for an early diagnosis in order to improve the prognosis

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.

Invasive fungal rhinosinusitis in patients with diabetes.

INTRODUCTION: We report the clinical and radiological features as well as outcomes of invasive fungal rhinosinusitis in patients with diabetes from a tertiary care center in North India. METHODOLOGY: All patients admitted with a diagnosis of invasive fungal rhinosinusitis with pre-existing or newly diagnosed diabetes from 1st January 2008 to 31st December 2015 were included. Hospital records were used to identify clinical features, biochemical investigations and treatment modalities used. The imaging findings were reported at baseline, 30, 60,90 and 120 days of admission and progression of disease was reported as static, worse or improved. The outcomes were sight loss and survival at end of hospital stay. RESULTS: 22 patients of invasive fungal sinusitis and diabetes were identified. At presentation, 5 had ketoacidosis, all of whom died at the end of hospital stay. Loss of vision in one eye was seen in 70% cases. The survival at end of hospital stay was 72.7% and at six months after end of study period was 57.8%. No patients had radiological improvement at day 30 imaging (including those who subsequently improved). CONCLUSION: Radiological improvement is not apparent before two months of therapy. Ketoacidosis is a predictor of mortality in invasive fungal sinusitis with diabetes.

Pediatric invasive fungal rhinosinusitis: An investigation of 17 patients.

PURPOSE: To investigate outcomes of pediatric patients at a single institution with invasive fungal rhinosinusitis (IFRS) and to determine variables that impact overall survival. METHODS: All pediatric patients at a large tertiary children's hospital diagnosed with IFRS confirmed by surgical pathology from 2009 to 2015 were retrospectively reviewed. Demographics, underlying diseases, symptoms, antifungal therapy, absolute neutrophil count (ANC), surgical management,and outcomes were analyzed. RESULTS: Seventeen patients were identified with IFRS with an average age of 8.7 years and 53% male. Hematologic malignancy was the most common (n = 13) underlying disease. The most common presenting symptoms were fever (82%) and congestion (41%). 15 patients had severe neutropenia (Absolute Neutrophil Count (ANC) < 500) within 2 weeks prior to diagnosis. The average ANC at time of diagnosis was 1420 cells/uL. 16 patients were treated with serial nasal endoscopy and debridement, while 1 patient was treated with an open approach. 16 received combination antifungals while 1 was treated with amphotericin monotherapy. The most common genus cultured was Fusarium (n = 6). The average number of surgical interventions was 3.4, with the average interval between interventions 6.2 days. 13 of 17 (76%) were cleared of IFRS. Overall survival at 6 months was 41%. CONCLUSION: Pediatric IFRS is a life-threatening disease that requires a coordinated surgical and medical approach. Despite a relatively high local control rate, overall mortality remains disappointingly high, reflecting the disease's underlying pathogenesis - lack of host defense and risk of disseminated fungal infection. Further investigation is necessary to reveal optimal management with regards to antifungal therapy, surgery, and utility of labs.

Complete surgical resection and short-term survival in acute invasive fungal rhinosinusitis.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a fulminant fungal infection seen in patients who are immunocompromised. Due to its rarity, there is little evidence regarding the appropriate antifungal treatment regimen, especially the degree of surgical intervention. OBJECTIVE: To assess factors that impact short-term survival in AIFR as defined by survival to hospital discharge and to develop a staging system to predict survival and complete surgical resection. METHODS: Fifty-four patients with histopathologically diagnosed AIFR who met inclusion criteria were identified between 1984 and 2014. Patient characteristics, disease extent, treatment modality, and short-term survival data were collected. Univariate analysis was performed to assess for factors associated with survival and increased likelihood of surgical resection. RESULTS: Of 52 patients with adequate documentation, 36 (69.2%) survived their hospital stay. Complete surgical resection was the only factor associated with improved survival (survival, 95.5%; p < 0.01). A surgical staging system was proposed to guide probability of complete resection and overall prognosis, with stage I disease limited to the nasal cavity, stage II involving the paranasal sinuses, stage III involving the orbit, and stage IV with skull base or intracranial extension. The χ2 analyses showed a decreased likelihood of complete surgical resection with stage III or IV disease compared with stage I (resection, 90.9%) (stage III resection, 37.5% [p = 0.01]; stage IV resection, 16.7% [p = 0.002]). There was a decreased likelihood of survival associated with increasing disease stage compared with stage I (survival, 100%) (stage II survival, 60% [p = 0.009]; stage III survival, 62.5% [p = 0.02]; stage IV survival, 54.6%, [p = 0.006]). CONCLUSION: Although further studies are needed to define specific treatment protocols, analysis of these data indicated that endoscopic sinus surgery with the goal of complete surgical resection may provide the best survival outcomes in select patients when complete surgical resection can be performed. Our staging system represents the first attempt to predict surgical success and prognosis in patients with AIFR.

Mortality risk in patients with chronic rhinosinusitis and its association to asthma.

BACKGROUND: Chronic rhinosinusitis (CRS) is a highly prevalent inflammatory condition, with significant effects on morbidity and quality of life. Given that other chronic inflammatory conditions have been associated with increased mortality risk, we sought to evaluate the relationship between mortality and CRS including the influence of asthma. Our objective was to determine if CRS, with or without asthma, is associated with altered risk of mortality. METHODS: Using a statewide population database, we retrospectively identified 27,005 patients diagnosed with CRS between 1996 and 2012, and 134,440 unaffected controls matched 5:1 on birth year and sex. Risk of mortality was determined from Cox models and Kaplan-Meier curves were used to compare survival. RESULTS: A significant interaction between CRS and asthma status was observed in which CRS appeared to confer a protective effect in asthma patients. Asthma, when present, increased mortality in CRS-negative controls (p-interaction < 0.0001). Independent of asthma status, CRS patients exhibited a decreased mortality risk (hazard ratio [HR] = 0.80; 95% confidence interval [CI], 0.74 to 0.85) compared to controls. However, in patients diagnosed at or before the median age of CRS onset (42 years) independent of asthma status, survival was not improved (HR = 0.98; 95% CI, 0.81 to 1.18). Risk of mortality was greater in CRS with nasal polyps (n = 1643) compared to 25,362 polyp-negative CRS patients (HR = 1.38; 95% CI, 1.09 to 1.77). CONCLUSION: CRS was associated with lower risk of mortality compared to controls, and appeared to mitigate increased mortality from asthma. We posit that better survival conferred by CRS may be secondary to treatment. However, the etiology of this relationship and the effect of CRS treatment on mortality are unknown.

[Managements and prognostic analyses in patients with invasive fungal rhinosinusitis].

OBJECTIVE: To evaluate the survival outcomes of invasive fungal rhinosinusitis by analyzing the clinical features. METHODS: A retrospective analysis was performed for cases of invasive fungal sinusitis proved by histological analysis between March 2006 and November 2015. All relevant factors including interval from the onset of symptoms to initiation of diagnosis, clinical characteristics, features of CT and MRI, treatment and prognosis were collected. A total of 18 patients (10 males; 8 females) were identified. The median age was 54 years old. Three patients suffered from acute invasive fungal sinusitis, while the other 15 suffered from chronic invasive fungal sinusitis. RESULTS: The mean duration between onset of symptoms and diagnosis was 5 months. The most common symptom was headache (10/18), followed by visual disturbance (7/18), nasal obstruction (4/18), facial numbness and pain (2/18) and diplopia(2/18). Two patients had diabetes mellitus; one patient had ankylosing spondylitis receiving immunosuppressive drugs treatment for one year. Four patients had the disease confined in the sinus. Complications of this disease included orbital apex involvement in 6 patients, intraorbital and optic nerve involvement in 3 patients, cavernous sinus involvement in 5 patients, pterygopalatine fossa and infratemporal fossa involvement in 5 patients, intracranial extension involvement in 3 patients. Fungal species included aspergillus (15 cases) and mucor (3 cases). Seventeen patients received intravenous antifungal therapy after surgery. The duration of follow-up ranged from 1 to 60 months. Two patients reoccurred and one patient died of the disease. CONCLUSION: Endoscopic debridement combined with intravenous antifungals is efficacious in the management of invasive fungal sinusitis.

Acute invasive fungal rhinosinusitis: Survival analysis and the prognostic indicators.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a highly mortal, progressive fungal infection of the paranasal sinuses and surrounding structures that is almost always seen in patients who are immunocompromised. Despite the use of newer antifungal treatments and early diagnosis, the prognosis of AIFR does not improve significantly. Due to the higher incidence of patients who are immunocompromised and have more complex disease, AIFR is a growing medical issue in tertiary medical centers. OBJECTIVE: The aim of this study was to present the outcomes and analyze the prognostic indicators of patients with AIFR who underwent surgery. METHODS: Between October 2009 and November 2014, 37 patients who underwent surgery for AIFR at a tertiary care university hospital were included in the study. Overall survival and disease-specific mortality and survival rates were calculated to estimate survival function. The impact of age, sex, underlying disease, extent of AIFR, applied medical treatment, and causative species (mucormycosis, aspergillosis) were also taken into consideration. Also, the effect of a variety of laboratory parameters, such as hemoglobin, leukocyte, neutrophil, lymphocyte, platelet, and C-reactive protein (CRP) levels, to survival were evaluated. RESULTS: The median follow-up time was 58 days (interquartile range = 304). Overall and disease-specific mortality rates were 64.9 and 51.4%, respectively. Fever was the most common symptom (86.5%), along with nasal obstruction and/or fullness (48.6%) and epistaxis (48.6%). Age and sex did not have a significant impact on survival (p > 0.05). Palate involvement was significantly associated with mortality (p < 0.05). According to the results of Cox, regression analysis for disease-specific mortality rate, leukocyte and neutrophil counts as well as CRP levels had a significant effect on survival function (p < 0.05). CONCLUSIONS: Palatal involvement was associated with a higher mortality in our study. Also, leukocyte counts, neutrophile counts, and CRP values had a significant impact on survival function. The reversal of the underlying disease and immunosuppression is as important as the medical and surgical treatment.

Acute Invasive Fungal Rhinosinusitis in Children With Hematologic Malignancies: Outcome of Surgical Treatment.

The incidence of acute invasive fungal rhinosinusitis (AIFR) is rising due to more aggressive chemotherapy and longer survival of immunosuppressed patients. Early diagnosis and appropriate but nonmutilating surgical treatment are particularly problematic in the pediatric population. This study aimed to evaluate the outcome of surgery for pediatric AIFR. Medical records of children surgically treated for AIFR between 1998 and 2014 were reviewed. Diagnosis was based on both histopathological and microbiological confirmation. Surgery was performed with curative intent and repeated for any resectable extension. The children underwent endoscopy and magnetic resonance imaging every 2 and 6 months, respectively, during the first postoperative year. Thirteen patients (2-18 years old) met the EORTC/MSG criteria for proven invasive fungal sinusitis; fungal invasion was diagnosed by preoperative biopsy and confirmed in the surgical specimen. All patients underwent an average of two endoscopic procedures (range 1-3), and four of them also underwent an open surgery. The local control rate was at least 79%. There was no facial disfiguration during follow-up (average 41 months). Although AIFR is still associated with high mortality, aggressive medical and surgical treatment provides local control in most cases. Fair outcome should encourage a maximal joint effort of pediatric hemato-oncologists and otorhinolaryngologists in the management of AIFR.

Prognostic factors for survival in patients with acute invasive fungal rhinosinusitis.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is an aggressive opportunistic infection with a high mortality rate. There are few reports that demonstrate an improvement in the overall prognosis. Furthermore, definite prognostic factors related to patient survival remain unclear. OBJECTIVE: The objective of this study was to evaluate the various clinical factors related to survival of patients with AIFR. METHODS: This is a retrospective case series with patients treated for AIFR between 1997 and 2013. A total of 45 patients with AIFR were enrolled for analysis. We evaluated demographics, clinical characteristics, and disease course. RESULTS: Mean age of patients was 59.6 years. AIFR developed most commonly in patients with immunocompromised host, such as diabetes (n = 23) or hematologic malignancy (n = 17). There were two main genera of fungus, Aspergillus (n = 30) and Mucor (n = 14). Headache, cranial neuropathy, visual loss, and orbital pain were the most common presenting symptoms. Overall survival was 53%. Underlying hematologic malignancy and diabetes were significantly associated with overall survival, and accompanying severe neutropenia and elevated C-reactive protein (CRP) were also related to poor prognosis. Initial presentation with facial swelling, involvement of nasal septum, or shorter symptom duration was also associated with survival reduction. Multivariate analysis revealed that CRP more than 5.50 mg/dL (Hazard ratio [HR], 9.04; p = .003) was an independent prognostic factor in patients with AIFR. CONCLUSIONS: Overall survival rate remained approximately 50% in patients with AIFR. The prognosis of AIFR is significantly influenced by underlying diseases, accompanying neutropenia, CRP levels, symptom duration, involvement of septum, and the presence of facial swelling. Elevation of CRP, in particular, was an independent predictor of poor outcomes and should be monitored appropriately.

The prognostic value of gadolinium-enhanced magnetic resonance imaging in acute invasive fungal rhinosinusitis.

OBJECTIVES: This study aimed to assess the prognostic value of gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) in acute invasive fungal rhinosinusitis (AIFRS) and offer recommendations for determining surgical extent based on loss of contrast enhancement (LoCE), which reveals tissue ischemia from fungal invasion. METHODS: Preoperative and postoperative Gd-enhanced MRI was evaluated in 21 patients with confirmed AIFRS who underwent wide debridement and antifungal therapy. Patients were subdivided by AIFRS-specific survival. LoCE and contrast enhancement (CE) of intrasinonasal and extrasinonasal sites in preoperative and postoperative MRI were compared between the two groups. RESULTS: All patients had preoperative intrasinonasal LoCE and CE lesions, which did not differ between survivors and non-survivors. Bone destruction on CT was detected in 8 of 16 survivors (50%) and 4 of 5 non-survivors (80%). Intrasinonasal LoCE lesions were completely removed by surgery in all cases. Postoperative extrasinonasal LoCE lesions were found in all non-survivors but no survivors (p < 0.001). However, postoperative intrasinonasal and extrasinonasal CE lesions were detected in both survivors and non-survivors (p = 0.119 and p = 0.111, respectively). In addition, remission of hematologic diseases at the time of diagnosis of AIFRS and blood sugar control in diabetic patients were significantly associated with AIFRS-specific survival (p = 0.028 and p = 0.023, respectively). CONCLUSIONS: LoCE lesions, which have to be surgically removed, should be screened using Gd-enhanced MRI for an earlier diagnosis of AIFRS, determination of surgical extent, and management of follow-up. Remnant LoCE lesions after surgery, active hematologic diseases, and poorly controlled blood sugar adversely affect the AIFRS-survival.