Microbial and clinical epidemiology of invasive fungal rhinosinusitis in hospitalized COVID-19 patients, the divergent causative agents.

Since COVID-19 spread worldwide, invasive fungal rhinosinusitis (IFRS) has emerged in immunocompromised patients as a new clinical challenge. In this study, clinical specimens of 89 COVID-19 patients who presented clinical and radiological evidence suggestive of IFRS were examined by direct microscopy, histopathology, and culture, and the isolated colonies were identified through DNA sequence analysis. Fungal elements were microscopically observed in 84.27% of the patients. Males (53.9%) and patients over 40 (95.5%) were more commonly affected than others. Headache (94.4%) and retro-orbital pain (87.6%) were the most common symptoms, followed by ptosis/proptosis/eyelid swelling (52.8%), and 74 patients underwent surgery and debridement. The most common predisposing factors were steroid therapy (n = 83, 93.3%), diabetes mellitus (n = 63, 70.8%), and hypertension (n = 42, 47.2%). The culture was positive for 60.67% of the confirmed cases, and Mucorales were the most prevalent (48.14%) causative fungal agents. Different species of Aspergillus (29.63%) and Fusarium (3.7%) and a mix of two filamentous fungi (16.67%) were other causative agents. For 21 patients, no growth was seen in culture despite a positive result on microscopic examinations. In PCR-sequencing of 53 isolates, divergent fungal taxons, including 8 genera and 17 species, were identified as followed: Rhizopus oryzae (n = 22), Aspergillus flavus (n = 10), A. fumigatus (n = 4), A. niger (n = 3), R. microsporus (n = 2), Mucor circinelloides, Lichtheimia ramosa, Apophysomyces variabilis, A. tubingensis, A. alliaceus, A. nidulans, A. calidoustus, Fusarium fujikuroi/proliferatum, F. oxysporum, F. solani, Lomentospora prolificans, and Candida albicans (each n = 1). In conclusion, a diverse set of species involved in COVID-19-associated IFRS was observed in this study. Our data encourage specialist physicians to consider the possibility of involving various species in IFRS in immunocompromised and COVID-19 patients. In light of utilizing molecular identification approaches, the current knowledge of microbial epidemiology of invasive fungal infections, especially IFRS, may change dramatically.

Invasive fungal rhinosinusitis (IFRS) may infect people with diabetes, cancer, or COVID-19. In this study, various types of fungi were identified from COVID-19-associated-IFRS, encouraging physicians to consider specific treatments.

Rinosinusitis micótica alérgica con destrucción de base de cráneo / Allergic fungal rhinosinusitis with skull base destruction

La sinusitis micótica alérgica es una enfermedad inflamatoria de la mucosa rinosinusal producida por hongos que pueden aislarse de la cavidad de nasal de individuos sanos. Se produce indirectamente por los hongos que actúan como antígeno y desencadenan una reacción inmunológica mediada por IgE que origina pólipos y una secreción mucosa espesa con detritus e hifas denominada mucina. Su presentación clínica más frecuente es una sinusitis crónica unilateral o bilateral con pólipos. Con menos frecuencia, las sustancias originadas por la desgranulación de los eosinófilos producen remodelación o destrucción ósea y la sinusitis puede simular una neoplasia. Se describe el caso clínico de un paciente que padeció una sinusitis micótica alérgica con destrucción ósea masiva de la base del cráneo y que tuvo extensión intracraneal extradural e intraorbitaria de la enfermedad. Fue tratado con éxito mediante cirugía y corticoides. (AU)

Allergic fungal sinusitis is an inflammatory disease of the rhinosinusal mucosa caused by fungi that can be isolated from the nasal cavity of healthy individuals. The pathology is produced indirectly by the fungus that acts as an antigen and triggers an IgE-mediated allergic reaction that causes polyps and a thick mucous discharge with detritus and hyphae called mucin. Its most common clinical presentation is unilateral or bilateral chronic sinusitis with polyps. Less commonly, substances originated by the degranulation of eosinophils cause bone remodeling or destruction, and sinusitis can simulate a neoplasia. We describe the clinical case of a patient who suffered from allergic fungal sinusitis with massive bone destruction of the skull base and who had intracranial, extradural and intraorbital extension of the disease. He was successfully treated with surgery and corticosteroids.Key words: allergic fungal sinusitis, intracranial extension, endoscopic surgery, transorbital transpalpebral approach. (AU)

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

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.

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.

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.

Paediatric mucormycosis: tailoring surgical strategies to compliment antifungal chemotherapy. Different strokes for different folks.

Children manifesting soft-tissue fungal infections are uncommonly seen, more so the subgroup of invasive soft-tissue mucormycosis. Invasive fungal infections in various organs respond differently and are often complicated by an immune-compromised host. Repeated and aggressive clearance of disease till an infection-clear margin is obtained is the mainstay of surgical therapy. This is coupled with appropriate antifungal therapy and the management of any underlying medical conditions. From our experience, we propose a surgical algorithm for therapy of soft-tissue mucormycosis in children.

Surgical resection for persistent localized pulmonary fungal infection prior to allogeneic hematopoietic stem cell transplantation: Analysis of six cases.

OBJECTIVE: Although invasive fungal disease (IFD) is an important complication in allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of surgery, including the role of surgical resection for persistent pulmonary fungal disease prior to allogeneic HSCT in the current era with a variety of available antifungal agents, is controversial. We investigated the role of surgical resection. METHODS: We retrospectively investigated six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT between April 2007 and June 2016 at our medical center. RESULTS: We present six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT. In our case series, three of four patients who were given a presurgical diagnosis of possible IFD were given a proven diagnosis after surgery, including two cases of invasive aspergillosis (IA) and one case of mucormycosis. All surgeries were performed by video-assisted thoracic surgery (VATS) for lobectomy without major complications. Recurrence of IFD was not observed after allogeneic HSCT in any of the six patients. CONCLUSION: Our experience indicated that surgical resection of persistent localized pulmonary lesions of IFD before allogeneic HSCT was helpful for obtaining a definitive diagnosis and might be useful for reducing recurrence after HSCT.

[Endoscopic transpterygoid intervention for lesions of lateral recess of sphenoid sinus in 4 cases(with literature review) ].

Objective: To investigate the anatomy and application of endoscopic transpterygoid intervention in lesions of lateral recess of sphenoid sinus(LRSS). Method: Four hospitalized patients with lesions of LRSS were studied. The clinical presentations included spontaneous cerebrospinal fuild(CSF) leakage in 2 cases, meningoencephaolece complicated CSF leakage in 1 case and chronic invasive fungal sphenoid sinusitis invading the base of the middle fossa in 1 case. Endoscopic transpterygoid intervention and repairment of skull base defects were performed under general anesthesia. Result: he operations were successfu1 in all patients. One patient suffered from postoperative palatal hypesthesia and all the symptoms mentioned above relieved gradually 6 months after operation. No recurrence was found during the follow-up ranging from 6 to 45 months(mean follow-up period,22.75 months).Conclusion: Endoscopic transpterygoid intervention in lesions of LRSS is a minimally invasive and safe surgical approach.

Results of endoscopic nasal surgery in the treatment of invasive fungal sinusitis in children with cancer and immunosuppression. / Resultados de cirugía endoscópica nasal en el tratamiento de sinusitis fúngica invasiva en niños con cáncer e inmunosupresión.

BACKGROUND AND OBJECTIVE: to describe the results of the treatment of invasive fungal sinusitis with nasal endoscopic surgery in an immunocompromised paediatric oncological population. METHODS: retrospective study of all patients diagnosed with invasive fungal sinusitis operated in the National Paediatric Oncology Unit between 2012 and 2016. Data taken from their medical history included: epidemiological characteristics, oncological diagnosis, haematological data, symptoms, tomographic studies, surgical interventions, results of pathology and cultures, medications received, complications, evolution and survival. RESULTS: 18 patients were identified, 7 male and 11 female. The average age was 12 years, 13 had a diagnosis of acute lymphocytic leukemia and 5 of acute myeloid leukemia. Seventeen patients presented severe neutropenia at the time of diagnosis. The most frequently identified aetiological agent was Aspergillus in 13 patients. In 16 patients (89%) the disease was controlled with nasal endoscopic surgery. Ten patients died due to unrelated causes throughout the study. DISCUSSION AND CONCLUSIONS: Invasive fungal sinusitis should be considered a medical emergency due to its high mortality. The diagnosis is based on a high index of suspicion in patients with predisposing factors (leukaemia, neutropenia, persistent fever, nasogastric tube) and endoscopic nasal evaluation. Antifungal medical treatment and aggressive nasal endoscopic surgery is indicated regardless of the patient's condition to reduce the fungal burden and associated high mortality. The treatment must be provided by a multidisciplinary team that includes paediatrics, haemato-oncology, infectology and otorhinolaryngology.

Scedosporium apiospermum invasive sinusitis presenting as extradural abscess.

INTRODUCTION: Chronic invasive fungal rhinosinusitis (CIFR) is a rare entity generally observed in immunodepressed subjects. The pathogen most frequently identified is Aspergillus spp. Imaging generally reveals invasive pseudoneoplastic features. We report a case of Scedosporium apiospermum (S. apiospermum) CIFR with an atypical clinical and radiological presentation. CASE REPORT: A 72-year-old immunocompetent man presented with chronic headache, neck pain and bilateral limitation of lateral gaze. Imaging revealed an isolated left sphenoidal lesion with marked bone changes and an extradural abscess over the clivus. Large endoscopic sphenoidotomy with type II rhinopharyngectomy was performed and the diagnosis of S. apiospermum CIFR was based on histological examination and fungal culture. The patient refused all medical treatment and did not present any signs of recurrence after 1 year of follow-up. DISCUSSION: S. apiospermum is a fungal species rarely isolated in CIFR. The present case was revealed by an atypical clinical presentation including isolated sphenoidal infection complicated by bilateral abducens nerve paralysis and extradural abscess. Imaging was also unusual, revealing features of fibrous dysplasia or bacterial osteomyelitis rather than the typical pseudoneoplastic appearance. The patient was successfully treated by surgery alone, which may therefore be sufficient treatment in immunocompetent subjects.

Reassessment of clinical implication of pretransplant surgical procedures for pulmonary invasive fungal lesions.

Dealing with the recent series of allogeneic hematopoietic stem cell transplantation (allo-SCT) performed this decade, we reassessed the clinical impact of pretransplant surgical procedures (SP) for pulmonary lesions of invasive fungal disease (IFD) on subsequent transplant outcome. We focused on the clinical outcomes of seven patients with pulmonary IFD who underwent segmentectomy (n = 4), lobectomy (n = 2) or abscess incision with drainage only (n = 1), and compared results to those of 21 patients carrying pulmonary IFD who never underwent invasive SP before allo-SCT. The rate of exacerbation of pulmonary lesions by 180 days after allo-SCT did not differ significantly between groups (32.2% vs 42.9%, P = 0.69). Moreover, no significant differences in non-relapse mortality (46.4% vs 42.3%, P = 0.93) or overall survival (53.6% vs 30.9%, P = 0.45) at 1 year were evident between groups. These results indicate that pretransplant SP for pulmonary lesions might have no survival benefit under the current antifungal prophylaxis or treatment modality.

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.

Surgical debridement for acute invasive fungal rhinosinusitis during the pre-engraftment phase of allogeneic hematopoietic stem cell transplantation: Two case reports.

RATIONALE: Surgical intervention may be not a contraindication for acute invasive fungal rhinosinusitis (AIFR) during the pre-engraftment period of allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENT CONCERNS: We present 2 cases involving patients with AIFR in the pre-engraftment phase of allo-HSCT. DIAGNOSES: Both patients received surgical debridement combined with systemic antifungal treatment. The biopsies identified the diagnosis of AIFR in these 2 cases. OUTCOMES: The 2 patients obtained normal hematopoiesis without recurrence of AIFR. LESSON: Our experience with these 2 cases suggests that prompt endoscopic surgical debridement is not an absolute contraindication for allo-HSCT recipients with AIFR during the pre-engraftment period. If permitted, urgent, radical, and aggressive but careful endoscopic debridement should be performed together with systemic antifungal treatment once AIFR has been diagnosed or suspected.

Advanced surgical technique for invasive fungal sinusitis: endoscopic orbit-sinus combined approach.

BACKGROUND: Invasive fungal sinusitis is usually associated with poor prognosis, but no clear guidelines have been established for surgical treatment. Here, we report the development and application of the endoscopic orbit-sinus combined approach (EOSCA), a novel surgical technique to approach the nasal cavity and orbit concurrently, in patients with invasive fungal sinusitis with orbital infiltration. MATERIAL AND METHODS: Two patients with invasive fungal sinusitis infiltrating the orbit underwent EOSCA. Transnasal endoscopy was performed for maximum debulking of tissues infiltrated by fungi in the nasal cavity and orbit, before making an incision into the palpebral conjunctiva. An endoscope was then inserted into the orbit through the incision in the palpebral conjunctiva to remove adipose tissue and muscles that had been infiltrated by fungi from the orbital regions where the transnasal approach was difficult or impossible. Another surgeon assisted the procedure by operating an endoscope concurrently via the nasal cavity (four-hands technique). RESULTS: We were able to remove lesions safely and with precision, preserving visual acuity and a functional eyeball in both cases. Currently, the patients are alive, with no postoperative complications, recurrence, or disfigurement. CONCLUSIONS: This novel method shows promise as a safe and reliable surgical procedure for patients with invasive fungal sinusitis infiltrating into the orbit, with no postoperative complications, recurrence, or disfigurement.

Utility of intraoperative frozen sections in surgical decision making for acute invasive fungal rhinosinusitis.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFRS) represents a fulminant, potentially fatal, disease process in immunocompromised patients. The diagnosis often rests on high index of clinical suspicion, with relative paucity of data on the diagnostic and therapeutic implications of intraoperative frozen sections. METHODS: Retrospective review was performed for 18 cases undergoing endoscopic sinus surgery for AIFRS. Reliability of intraoperative frozen section diagnosis was evaluated for all patients using final pathology as the gold standard. RESULTS: A total of 66 frozen sections were performed. Diagnostic accuracy of frozen sections illustrated sensitivity of 72.7% (95% confidence interval [CI], 0.57 to 0.85), specificity of 100% (95% CI, 0.85 to 1.00), positive predictive value (PPV) of 100% (95% CI, 0.89 to 1.00), and negative predictive value (NPV) of 64.7% (95% CI, 0.46 to 0.80). There was no statistically significant difference in sensitivity of frozen sections in cases of Mucor and Aspergillus at 68.8%% and 76.2%, respectively (p = 0.61). CONCLUSION: This study represents the largest series assessing the diagnostic accuracy of frozen section analysis in AIFRS. Frozen section analysis is an effective tool for guiding intraoperative decision making in patients with AIFRS with a high PPV. A Low NPV underscores the importance of clinical suspicion and intraoperative decision making based on endoscopic findings when negative frozen section results are encountered. Further, frozen section analysis appears to be equally effective in detecting either Mucor or Aspergillus.