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.

A multi-institutional review of outcomes in biopsy-proven chronic invasive fungal sinusitis.

BACKGROUND: Chronic invasive fungal sinusitis (CIFS) is a rare, life-threatening infection of the nose and sinuses. This study aims to identify factors that impact survival in 1 of the largest cohorts to date. METHODS: Pathology records were reviewed for biopsy-proven CIFS from 3 tertiary academic institutions from 1995 to 2016. Variables were analyzed using log-rank survival analysis. Univariate Cox regression was performed at 1 and 12 months. RESULTS: Thirty-eight patients were included. Hematologic malignancy and diabetes were the most common underlying diseases (32% each). Aspergillus was the most common fungus (63%). Greater than 75% of the patients had an absolute neutrophil count (ANC) >1000 at the time of diagnosis. Overall survival at 1, 6, and 12 months was 89%, 68%, and 48%, respectively. In univariate analysis, factors associated with worse survival included: ANC <500 at 12 months (hazard ratio [HR] 4.8; p = 0.01), ANC <1000 at 12 months (HR 5.8; p = 0.001), and recent chemotherapy (HR 4; p = 0.01). The following factor was associated with improved survival in univariate analysis: ANC as a linear variable in the entire cohort (HR 0.7; p = 0.005). CONCLUSION: We present a multi-institutional case-series of CIFS and long-term follow-up. ANC <1000 at time of diagnosis and recent chemotherapy (within 1 month of diagnosis) are associated with poorer survival, whereas a rising ANC >1000 is associated with improved survival at 12 months. Further prospective studies are needed to further define factors that affect outcomes.

Complications of sinusitis: An 80-case series from the ENT and neurosurgery departments of the Fann university hospital center of Dakar, Senegal.

INTRODUCTION: Locoregional complications of sinusitis are dominated by oculo-orbital and/or cranioencephalic manifestations that may be life-threatening or jeopardize functional prognosis. The aim of this study was to report epidemiological, diagnostic and therapeutic aspects. MATERIALS AND METHODS: A retrospective study included inpatients managed for sinusitis complications in the ENT and neurosurgery departments of the Fann university hospital center in Dakar, Senegal between January 1, 2005 and December 31, 2016. RESULTS: In all, 80 files were collected. Mean age was 18.5 years, with male predominance. Mean time to treatment was 18.2 days. Cranio-encephalic complications were the most frequent (54 cases; 67.5%): mainly subdural empyema (30 cases) and brain abscess (10 cases). Seventeen patients (21.25%) had oculo-orbital complications: mainly orbital cellulitis (52.9%) and preseptal cellulitis (29.4%). Nine patients (11.25%) had both cranioencephalic and oculo-orbital complications. Acute sinusitis (82.5%) was the main cause of complications. 52.5% of patients showed pansinus involvement. Medical treatment consisted in broad-spectrum antibiotic therapy combining third-generation cephalosporins, metronidazole and gentamycin in cranio-encephalic complications and clavulanic acid and metronidazole in oculo-orbital complications. Thirty-four patients (42.5%) underwent surgical sinus drainage. Neurosurgical drainage was performed in 35 cases (43.75%). Post-treatment course was marked by 6.25% mortality (5 cases) and 16.25% sequelae. CONCLUSION: With 6.25% mortality and a high rate of functional sequelae, complications of sinusitis are a serious concern in our region. Improving prognosis requires earlier management and better coordination between health professionals.

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.

Invasive Fungal Sinusitis: Risk Factors for Visual Acuity Outcomes and Mortality.

PURPOSE: Invasive fungal sinusitis is a rare but potentially lethal disease that primarily affects immunocompromised patients. The purpose of this study was to review an academic medical center's experience in the presentation, diagnosis, and treatment of invasive fungal sinusitis. METHODS: A retrospective chart review was performed at a single institution over a 17-year period. Medical records, radiographic imaging, and operative reports were analyzed. Bivariate and multivariable analyses were performed to determine factors that affected visual acuity outcomes and mortality. RESULTS: Fifty-five patients with histopathologically confirmed invasive fungal sinusitis were included. The average duration of follow up was 1.8 ± 2.6 years (range: 1 week to 10 years). The most common causes of immunosuppression were hematologic malignancy (45%), diabetes (31%), and organ transplantation (9%). At presentation, 35% of individuals were neutropenic (absolute neutrophil count < 500/µl). All patients received systemic antifungal treatment. A surgical intervention was performed on 50 patients (91%), and all but one had functional endoscopic sinus surgery. Nine (16%) patients underwent orbital exenteration. Multivariable analysis of visual acuity outcomes demonstrated that individuals infected with Zygomycota had 6-7 lines worse vision than those infected with Ascomycota (mean difference in logMAR 0.66, 95% confidence interval 0.27 to 1.06, p = 0.001). Patients who had functional endoscopic sinus surgery had 7-8 lines better visual acuity than those without functional endoscopic sinus surgery (mean difference in logMAR -0.76, 95% confidence interval -1.13 to -0.38, p < 0.001). The overall death rate due to infection was 24%. Bivariate models demonstrated no difference in mortality in patients receiving exenteration versus those who did not (p = 0.14). Multivariable analysis of mortality demonstrated that neutropenia increased mortality (adjusted odds ratio 10.05, 95% confidence interval 1.49 to 67.67, p = 0.02). Having a greater number of surgeries was associated with an increased rate of survival (adjusted odds ratio 0.39, 95% confidence interval 0.15 to 0.96, p = 0.04). CONCLUSIONS: Invasive fungal sinusitis is an aggressive disease with significant mortality. Patients with neutropenia had a lower rate of survival, and infection with Zygomycota was associated with worse visual acuity outcomes. Those having functional endoscopic sinus surgery had better final visual acuity, and an increased number of surgeries was associated with a decreased chance of death. Exenteration yielded no observed survival benefit.Endoscopic sinus debridement portends better visual acuity outcomes in patients with invasive fungal sinusitis, whereas exenteration yields no difference in survival benefit.

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.

The role of galactomannan Aspergillus antigen in diagnosing acute invasive fungal sinusitis.

BACKGROUND: Pathologic diagnosis remains the gold standard for final diagnosis of acute invasive fungal sinusitis (AIFS); however, other less invasive tests could suggest the presence of AIFS in at-risk populations where early diagnosis is crucial. Serum galactomannan Aspergillus antigen has been shown to correlate with a diagnosis of invasive pulmonary aspergillosis; however, it has not adequately been evaluated in regard to AIFS. The objective of this study is to evaluate the statistical relevance of galactomannan in predicting diagnosis of AIFS. METHODS: This study was a retrospective review of pathologic records using Co-Path from 2006 to 2017, incorporating 2 separate searches with designated criteria identifying patients who received pathologic evaluation for invasive fungal sinusitis. Electronic medical records were subsequently reviewed. After exclusions isolating at-risk populations and removing duplications, 78 cases were reviewed using the indicated search criteria. Of these, 38 met further criteria of having had both pathologic evaluation and galactomannan analysis. Statistical variables were assessed, as well as all-cause mortality. Peak and closest galactomannan levels were evaluated. RESULTS: Overall, galactomannan had a sensitivity of 44.8% (95% confidence interval [CI], 26.5% to 64.3%), specificity of 100% (95% CI, 66.4% to 100%), positive predictive value of 100% (95% CI, 74.3% to 100%), and negative predictive value of 36% (95% CI, 18.0% to 57.5%). No significant association was observed in galactomannan status and mortality in this patient population. CONCLUSION: Positive serum galactomannan can be an indication of AIFS in patients with a high clinical suspicion. In our study, a positive galactomannan always correlated with a positive pathologic diagnosis. However, given its low sensitivity, one must use caution in relying on galactomannan as a screening tool in diagnosis of AIFS.

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.

A multi-institutional review of outcomes in biopsy-proven acute invasive fungal sinusitis.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is a rare, aggressive infection occurring in immunocompromised patients. In this study we examined factors that affect survival in AIFS, and whether immune-stimulating therapies (IST) improve survival. METHODS: Pathology records of biopsy-proven AIFS were reviewed from 3 academic institutions from 1995 to 2016. Univariate and multivariate Cox regressions were performed at 1 and 3 months from diagnosis. RESULTS: One hundred fourteen patients were included; 45 received IST. In the univariate analysis, the following factors were associated with worse survival: hematologic malignancy (3-month hazard ratio [HR], 3.7; p = 0.01); recent chemotherapy (within 1 month of AIFS diagnosis) (3-month HR, 2.3; p = 0.02); recent bone marrow transplant (BMT) (3-month HR, 2.5; p = 0.02); and infection with atypical fungi (1-month HR, 3.1; p = 0.04). The following were associated with improved survival in univariate analysis: increasing A1c% (1-month HR, 0.7; p = 0.01) and surgical debridement (1-month HR, 0.1; p = 0.001). One third of patients with a hematologic malignancy had an absolute neutrophil count (ANC) >1000 at the time of diagnosis. ANC was not associated with prognosis in these patients. The following were associated with worse survival in multivariate analyses: hematologic malignancy; recent chemotherapy; atypical organisms; and cavernous sinus extension. In multivariate analyses, IST was associated with a 70% reduction in mortality at 1 month (p = 0.02). CONCLUSION: We presented the largest series of AIFS. Further studies are needed to examine the importance of ANC in diagnosis and prognosis. Patients diagnosed with atypical organisms may be at higher risk of death. IST likely improves short-term survival, but prospective studies are needed.

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.

Invasive fungal sinusitis in the pediatric population: Systematic review with quantitative synthesis of the literature.

BACKGROUND: Invasive fungal sinusitis (IFS) represents an often fatal condition within the pediatric population. In an effort to characterize demographics, treatment modalities, and prognostic factors, we performed a systematic review. METHODS: We systematically reviewed EMBASE, Medline, TRIPdatabase, SCOPUS and the Cochrane database for invasive fungal nasal and sinus infections limited to individuals <18 years of age. Case series including 3 or more patients were included. Demographics, treatment and outcomes were analyzed using R Gui statistical software. RESULTS: Twelve studies met inclusion criteria (103 patients). There was male preponderance of 48.5% with median age of 11 years old. Majority of patients had underlying leukemia (44.6%). Aspergillus was the predominant organism (47%). Isolated nasal findings occurred in 14% of patients and nasal findings occurred in 49% overall. Absolute neutrophil count (ANC) of immunocompromised patients was below 600 in most patients (99%). Average and median length of neutropenia was 2 weeks. All patients were prescribed amphoterocin with 50% as single medicinal therapy. Surgery occurred in 82.8% of cases. The mortality rate was 46%. Univariate analysis identified presenting with facial pain as a negative predictor of overall mortality (OR 0.296, 95% CI: 0.104-0.843, p < 0.05). CONCLUSION: Mortality remains high in pediatric patients with IFS. An ANC of <600 occurred in the majority of immunocompromised patients at a duration of 2 weeks. Presenting with facial pain was a negative predictor of mortality. Many studies label this condition as invasive fungal sinusitis; however, approximately one seventh presented with only nasal findings and half overall had nasal involvement.