Overall survival and prognostic factors in diabetic patients with invasive fungal rhinosinusitis.

BACKGROUND: Patients with diabetes mellitus (DM) are susceptible to invasive fungal rhinosinusitis (IFRS). The mortality rate of IFRS varies greatly among the patients with DM. OBJECTIVE: To identify the prognostic factors for the overall survival of patients with DM and IFRS. METHODS: A retrospective study was conducted in four tertiary hospitals in Thailand, Malaysia and Myanmar. Patients diagnosed with IFRS and DM from 2008 to 2019 were identified. The outcome was the overall survival. Variables analyzed for risk factors were age, HbA1C level, ketoacidosis, white blood cell count, hyperglycemia, duration of DM, current use of diabetic medications, serum creatinine level, and the extensions of IFRS to the orbit, the cavernous sinus and intracranial cavity. RESULTS: Sixty-five diabetic patients with IFRS (age 57.9 ± 13.4 years, male 60%) were identified. The mortality rate was 21.5%. The extensions of IFRS to the cavernous sinus (hazard ratio 5.1, 95% CI [1.4-18.2], p = 0.01) and intracranial cavity (hazard ratio 3.4, 95% CI [1.1-11.3, p = 0.05) predicted mortality. Current use of diabetic medications decreased the mortality risk (hazard ratio 0.2, 95% CI [0.1-0.9], p = 0.03). The 6-month overall survival of the patients with and without the cavernous sinus extension were 51.4% and 83.6%, (p = 0.001), with and without intracranial extension 53.3% and 88.9%, (p = 0.001), and with and without current diabetic medications 82.3% and 57.5%, respectively (p = 0.045). CONCLUSIONS: The extensions of IFRS to the cavernous sinus and intracranial cavity increased the risk of death in patients with DM. Survival was primarily related to current use of diabetic medications.

Predictive factors for invasive fungal rhinosinusitis in diabetic patients: Systematic review and data re-analysis.

This systematic review aims to identify prognostic factors for the overall survival of invasive fungal rhinosinusitis (IFRS) in patients with diabetes using original data from the existing published articles. Systematic searches of Medline, EMBASE, and Cochrane Library databases were performed to include articles from 1988 to 2019 using the terms: "fung*" AND "rhinosinusitis" AND "invasive" AND "diabetes OR ketoacidosis". Data from 258 diabetic patients with IFRS (mean age 55.9 years, 55.6% male, 124 studies) were extracted for data analysis. The mortality rate was 31.8%. Seven variables: plasma glucose level, HbA1C, ketoacidosis, leukopenia, serum creatinine level, duration of diabetes, and the cavernous sinus extension were assessed. Univariate analysis was done for each variable and revealed that the cavernous sinus extension was a significant risk factor. Multivariable logistic regression analysis confirmed that the cavernous sinus extension independently predicted mortality in patients with diabetes (hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.2 to 5.4, p = 0.01). Kaplan Meier curve and Log-rank test were used for analyzing survival outcomes. The twelve-month overall survival rate of the patients with the cavernous sinus extension was 43.9% compared to 73.9% for the patients without the cavernous sinus extension (p = 0.01). Appropriate treatment of this condition could enhance the survival outcomes.

Immune response to fungi in diabetic patients with invasive fungal rhinosinusitis.

This article aims to review the literature regarding the immune response to fungi in diabetic patients with invasive fungal rhinosinusitis. Systematic searches of Medline, EMBASE, and Cochrane Library databases were performed to include articles from 1988 to 2019 which assessed 'immune response to fungi in normal host', 'immune deficiency in diabetes mellitus', or 'immune response to fungi in diabetic patients'. Fungal cell wall activated pattern recognition receptors, resulting in recruitment of innate immune cells and an adaptive immune response. In diabetes mellitus, the expression of class I major histocompatibility complex was reduced. A hyperglycemic state decreased vascular dilation and the formation of neutrophil extracellular traps. The structure of complement was altered with consequent inhibition of complement fixation to bacteria. The balance between complement activation and restriction was broken. Hyperglycemia activated protein kinase C which inhibited neutrophil migration, decreased production of polymorphonuclear cells, decreased chemotaxis and decreased phagocytic activity. Germination and filamentous growth of the fungus within a diabetic host caused angioinvasion, vascular thrombosis and necrosis. Patients with diabetic ketoacidosis had elevated levels of serum iron which regulated endothelial cell damage. Iron and the overexpression of glucose-induced glucose-regulated protein 78 enhanced the susceptibility of endothelial cells to fungi and induced fungal invasion. In summary, associations among the immunopathology of diabetes, the pathophysiology of fungal infections, and the therapeutic outcomes must be considered in clinical practice. In diabetic patients, both the humoral and cellular immune responses of innate and adaptive immune systems were defective. Treatments should aim for the immune function restoration.