Development and preclinical validation of 2-deoxy 2-[18F]fluorocellobiose as an Aspergillus-specific PET tracer.

The global incidence of invasive fungal infections (IFIs) has increased over the past few decades, mainly in immunocompromised patients, and is associated with high mortality and morbidity. Aspergillus fumigatus is one of the most common and deadliest IFI pathogens. Major hurdles to treating fungal infections remain the lack of rapid and definitive diagnosis, including the frequent need for invasive procedures to provide microbiological confirmation, and the lack of specificity of structural imaging methods. To develop an Aspergillus-specific positron emission tomography (PET) imaging agent, we focused on fungal-specific sugar metabolism. We radiolabeled cellobiose, a disaccharide known to be metabolized by Aspergillus species, and synthesized 2-deoxy-2-[18F]fluorocellobiose ([18F]FCB) by enzymatic conversion of 2-deoxy-2-[18F]fluoroglucose ([18F]FDG) with a radiochemical yield of 60 to 70%, a radiochemical purity of >98%, and 1.5 hours of synthesis time. Two hours after [18F]FCB injection in A. fumigatus pneumonia as well as A. fumigatus, bacterial, and sterile inflammation myositis mouse models, retained radioactivity was only seen in foci with live A. fumigatus infection. In vitro testing confirmed production of ß-glucosidase enzyme by A. fumigatus and not by bacteria, resulting in hydrolysis of [18F]FCB into glucose and [18F]FDG, the latter being retained by the live fungus. The parent molecule was otherwise promptly excreted through the kidneys, resulting in low background radioactivity and high target-to-nontarget ratios at A. fumigatus infectious sites. We conclude that [18F]FCB is a promising and clinically translatable Aspergillus-specific PET tracer.

The Aspergillus galactomannan Ag VIRCLIA® Monotest and the sõna Aspergillus galactomannan lateral flow assay show comparable performance for the diagnosis of invasive aspergillosis.

BACKGROUND: Rapid galactomannan tests, such as the sõna Aspergillus GM Lateral Flow Assay (GM-LFA) and the Aspergillus Galactomannan Ag VIRCLIA® Monotest (GM-Monotest), which are suitable for the analysis of single samples, have the potential to accelerate diagnosis of invasive aspergillosis (IA). OBJECTIVES: To compare the performance of the GM-Monotest and the GM-LFA for the diagnosis of IA. PATIENTS/METHODS: Two patient cohorts were analysed: adults who had received an allogeneic haematopoietic stem-cell transplant (alloHSCT-cohort) and patients with proven/probable IA from a 5-year period (cross-sectional IA-cohort). In the alloHSCT-cohort, weekly serum samples were tested, whereas in the cross-sectional IA-cohort sera and bronchoalveolar lavage fluids were analysed. The diagnostic performance was calculated using two definitions for positivity: (1) a single positive GM result and (2) at least two positive GM results from consecutive samples. IA classification followed EORTC/MSG 2019. RESULTS: The alloHSCT-cohort included 101 patients. Four had proven/probable IA, 26 possible IA and 71 no IA. The specificity for one positive serum and two consecutively positive sera was 88.7% and 100% (GM-Monotest) and 85.9% and 98.6% (GM-LFA). Comparison of ROC curves in the alloHSCT-cohort showed no significant difference. The cross-sectional IA-cohort included 59 patients with proven/probable IA. The sensitivity for one positive sample and two consecutively positive samples was 83.1% and 55.1% (GM-Monotest) and 86.4% and 71.4% (GM-LFA). CONCLUSIONS: Both assays showed comparable diagnostic performance with a higher sensitivity for the GM-LFA if two consecutive positive samples were required for positivity. However, due to poor reproducibility, positive GM-LFA results should always be confirmed.

An immunocompetent lady with invasive aspergillosis presenting as disseminated lesions: a case report.

BACKGROUND: Invasive Aspergillosis is a fungal infection caused by Aspergillus species, typically posing life-threatening risks to immunocompromised individuals. While occurrences in immunocompetent hosts are rare, a recent case report documented fulminant pulmonary aspergillosis in an immunocompetent patient during autopsy. Here, we present a case of invasive aspergillosis in an immunocompetent woman, manifesting with disseminated lesions. CASE PRESENTATION: A 29-year-old Asian woman presented to our hospital in March 2022, reporting chest pain and shortness of breath persisting for two months. Upon examination, she appeared thin and unwell, with no notable abnormalities otherwise. Radiographic imaging revealed an ill-defined lesion in her left lung. Subsequent bronchoscopy and lavage were performed, followed by initiation of empirical antibiotic therapy. Lavage results were negative for gram staining, culture, and ZN staining for AFB, but revealed numerous septate hyphae on fungal smear. Histopathological examination indicated chronic granulomatous inflammation with septal fungal hyphae, indicative of aspergillosis. Subsequent culture confirmed Aspergillus species, prompting initiation of voriconazole therapy. Remarkably, the patient exhibited significant improvement, with weight gain and restored appetite observed within a short period. Within 2 months of treatment, her symptoms resolved, and she resumed near-normal daily activities. CONCLUSION: This case highlights the diagnosis of aspergillosis in an immunocompetent individual presenting with disseminated nodular lesions across the lungs, mediastinum, and abdomen. Clinicians should maintain a high index of suspicion for aspergillosis in cases of non-resolving pneumonia and disseminated nodular lesions, even in patients lacking traditional predisposing factors.

Aspergillosis coinfection in patients with proven mucormycosis.

Although research on aspergillosis and mucormycosis confection is important to optimize antifungal therapy, data on this issue is scarce. Thus, we systematically investigated aspergillosis coinfection in patients with proven mucormycosis. Medical records of adult patients with proven mucormycosis whose formalin-fixed paraffin-embedded (FFPE) tissue sections were available, in a tertiary hospital from August 2007 to July 2023 were retrospectively reviewed to assess coinfection with aspergillosis. We noted cultures of fungi from sterile and non-sterile sites and performed polymerase chain reaction (PCR) assays on FFPE tissues to detect Aspergillus- and Mucorales-specific DNA. Sixty-seven patients with proven mucormycosis, including 12 (18%) with a positive culture of the mucormycosis agent from sterile site cultures, were enrolled. Fungal cultures from sterile and non-sterile sites revealed Aspergillus spp. growth in nine (13%) of the 67 patients, including two sterile and seven non-sterile cultures. The fungal PCR analysis from the FFPE sections was positive for Aspergillus-specific PCR in five (7%) and positive for both Aspergillus- and Mucorales-specific PCR results in eight (12%). Overall, 21 (31%) of the 67 patients with proven mucormycosis had microbiologic and/or molecular evidence of aspergillosis coinfection. Positive blood or bronchoalveolar lavage fluid galactomannan results were more common in the coinfection group (67% [14/21]) than in the mucormycosis group (37% [17/46], P = .024). No significant difference in mortality between the two groups was observed. Approximately one-third of patients with proven mucormycosis exhibited molecular and/or microbiologic evidence of aspergillosis coinfection. Further research is needed to identify patients with aspergillosis and mucormycosis coinfections, for optimal antifungal therapy.

The study aims to investigate the coinfection between mucormycosis and aspergillosis. Key findings reveal that approximately 31% of patients demonstrated evidence of coinfection, which emphasizes the importance of considering both pathogens in diagnosis and treatment decisions.

Interplay between host humoral pattern recognition molecules controls undue immune responses against Aspergillus fumigatus.

Pentraxin 3 (PTX3), a long pentraxin and a humoral pattern recognition molecule (PRM), has been demonstrated to be protective against Aspergillus fumigatus, an airborne human fungal pathogen. We explored its mode of interaction with A. fumigatus, and the resulting implications in the host immune response. Here, we demonstrate that PTX3 interacts with A. fumigatus in a morphotype-dependent manner: (a) it recognizes germinating conidia through galactosaminogalactan, a surface exposed cell wall polysaccharide of A. fumigatus, (b) in dormant conidia, surface proteins serve as weak PTX3 ligands, and (c) surfactant protein D (SP-D) and the complement proteins C1q and C3b, the other humoral PRMs, enhance the interaction of PTX3 with dormant conidia. SP-D, C3b or C1q opsonized conidia stimulated human primary immune cells to release pro-inflammatory cytokines and chemokines. However, subsequent binding of PTX3 to SP-D, C1q or C3b opsonized conidia significantly decreased the production of pro-inflammatory cytokines/chemokines. PTX3 opsonized germinating conidia also significantly lowered the production of pro-inflammatory cytokines/chemokines while increasing IL-10 (an anti-inflammatory cytokine) released by immune cells when compared to the unopsonized counterpart. Overall, our study demonstrates that PTX3 recognizes A. fumigatus either directly or by interplaying with other humoral PRMs, thereby restraining detrimental inflammation. Moreover, PTX3 levels were significantly higher in the serum of patients with invasive pulmonary aspergillosis (IPA) and COVID-19-associated pulmonary aspergillosis (CAPA), supporting previous observations in IPA patients, and suggesting that it could be a potential panel-biomarker for these pathological conditions caused by A. fumigatus.

A retrospective Italian analysis on the characteristics of invasive fungal infections in the intensive care unit setting: CHARTER-IFI study.

BACKGROUND: Invasive fungal infections (IFI), prevalent in critically ill ICU patients, have gained attention due to post-COVID-19 epidemiological shifts. Notably, COVID-19-associated aspergillosis and candidiasis pose significant risks. WHO recognises key fungal pathogens, emphasising the need for enhanced research and interventions. METHODS: The CHARTER-IFI study retrospectively examines 186,310 individuals admitted to ICUs in Italy from 01/01/2012-01/09/2023, utilising administrative databases covering around 10 million inhabitants. Adult patients were included having at least one ICU discharge diagnosis of IFI at their first IFI-related hospitalisation and having at least 12 months of available data prior to this hospitalisation. RESULTS: A total of 746 IFI patients discharged from ICU (incidence of 4.0 per 1000 ICU-hospitalised patients), were included. Median age was 68 years, 63% were males, and the overall Charlson Comorbidity Index was 2.2. The top three diagnoses were candidiasis (N = 501, 2.7/1000 ICU-hospitalised patients), aspergillosis (N = 71, 0.4/1000), and pneumocystosis (N = 55, 0.3/1000). The evaluation of the comorbidity profile in IFI patients revealed the presence of hypertension (60.5%), use of systemic GC/antibacterials (45.3% during 12 months before and 18.6% during 3 months before hospital admission), cancer (23.1%), diabetes (24.3%) and cardiovascular diseases (23.9%). The mean (±SD) length of hospitalisation in ICU was 19.9 ± 24.1 days (median 11 days), and deaths occurred in 36.1% of IFI patients (within 30 days from discharge). CONCLUSIONS: This retrospective analysis among ICU-hospitalised patients described the burden of IFI in ICU, and its understanding could be crucial to strengthen surveillance, investments in research, and public health interventions as required by WHO.

Skull Base Aspergillus Infection Mimicking Tumor Recurrence: A Nasopharyngeal Carcinoma Case Study.

ABSTRACT: We report a case of recurrent nasopharyngeal carcinoma postnasopharyngectomy, presenting with headaches. MRI revealed abnormal signals of the clivus with enhancement, and FDG PET/CT indicated intense uptake in the nasopharynx, clivus, and left neck lymph nodes. Bone SPECT/CT showed bony erosion and uptake in bilateral skull base areas. Biopsy confirmed aspergillosis. Despite the challenges in distinguishing tumor invasion from Aspergillus infection on MRI, bone SPECT/CT, and FDG PET/CT, the short postsurgery period and extensive uptake suggested skull base osteomyelitis.

Pseudomonas and aspergillus symbiotic coinfections in a case of chronic obstructive pulmonary disease and diabetes mellitus.

Coinfection of Pseudomonas and Aspergillus has not been previously reported in patients with chronic obstructive pulmonary disease (COPD). A middle-aged, thinly built woman (Body Mass Index: 18.1 kg/m²) who smokes bidi (a type of tobacco) and has a history of exposure to open log fires for cooking, has been suffering from COPD for the last 4 years. She has been taking inhaled betamethasone and tiotropium. Additionally, she had uncontrolled diabetes for a few months. She presented with fever, productive cough, shortness of breath and chest pain for 5 days. She required non-invasive ventilation support for type-2 respiratory failure. Chest X-ray and CT confirmed pneumonia, cavities and abscesses in both lungs. Repeated sputum and bronchoalveolar lavage confirmed coinfections with Pseudomonas aeruginosa and Aspergillus fumigatus, respectively. Along with supportive therapy, she was treated with tablet levofloxacin and injection amikacin for 6 weeks based on culture sensitivity reports, and capsule itraconazole for 6 months. She recovered completely to her baseline COPD and diabetes status. This case study confirms that coinfections can occur in COPD and diabetes, highlighting the need for clinicians to be vigilant for the possibility of such symbiotic coinfections.

[Research advances on the mechanism of immune regulation of interferon in Aspergillus infection].

Pulmonary aspergillosis is a serious pulmonary fungal infectious disease. It is difficult to manage and has limited treatment options. Existing anti-aspergillus medications have high rates of treatment failure and increased drug resistance, making it difficult to meet the clinical requirements. Therefore, the development of new, effective treatment programs is critical. According to research, interferons play an important role in the body's immune response to bacterial and viral infectious diseases. Inadequate interferon expression or dysfunction can put the body at risk for certain infectious diseases. Interferon has been used in clinical trials to prevent or treat infectious diseases. In recent years, researchers have focused on the immunological role of interferon in Aspergillus infections and its potential for clinical application. This review summarized the most recent advances in the immunoregulatory mechanisms of interferon and its clinical application in Aspergillus infections.

Comparison of galactomannan lateral flow assay and enzyme immunoassay to identify Aspergillus spp. in bronchoalveolar lavage fluid.

Aspergillus species can colonize and infect immunocompetent and immunocompromised hosts. Conventional fungal identification depends on microscopic analysis and microorganism medium growth. Other diagnostic methods, non-growth dependent, to invasive fungal infections, are the biomarkers that detect circulating polysaccharides, for example, 1-3-ß-d-Glucan and galactomannan. Both are polysaccharides present on the external layer of fungi cell wall and can be detected in clinical samples during the growth of the fungus in the patient. This study aimed to compare the galactomannan detection of Lateral Flow Assay and Enzyme Immunoassay methods in Bronchoalveolar Lavage Fluid. The galactomannan antigen in Bronchoalveolar Lavage Fluid was measured using Enzyme Immunoassay according to the manufacturer's instructions (PLATELIA ASPERGILLUS™ BioRad) and, using a Lateral Flow Assay according to the manufacturer's instructions (Galactomannan LFA IMMY©). The 71 samples were Bronchoalveolar Lavage Fluid of patients hospitalized at Unicamp Clinical Hospital between 2019 and 2021; of these samples 12/71 (16.9 %) resulted in positive Galactomannan-Lateral Flow Assay. In contrast, Galactomannan-Enzyme Immunoassay resulted as positive in 9/71 (12.6 %) samples, a difference that showed not significant statistically (p-value = 0.36) Comparing both assays' results identified 8 divergences between them, about 11 % of the total sample. The Sensitivity (73.3 %), Specificity (92.35 %), Positive Predictive Value (62.85 %) and Negative Predictive Value (95.15 %) of Lateral Flow Assay were calculated using the Galactomannan Enzyme Immunoassay as standard. The Lateral Flow Assay demonstrated good results when compared with the Enzyme Immunoassay.

New developments in Aspergillus fumigatus and host reactive oxygen species responses.

Aspergillus fumigatus is a filamentous fungus abundant in the environment and the most common causative agent of a spectrum of human diseases collectively termed aspergillosis. Invasive pulmonary aspergillosis is caused by deficiencies in innate immune function that result in the inability of the host to clear inhaled Aspergillus conidia that then germinate and form invasive hyphae. Myeloid cells, and their ability to generate reactive oxygen species (ROS), are essential for conidia clearance from the host. To combat ROS, A. fumigatus employs an expansive antioxidant system, though how these canonical antioxidant mechanisms contribute to infection initiation and disease progression remain to be fully defined. Recent research has identified noncanonical pathways in the A. fumigatus ROS response and new host populations with ROS deficiencies that are at-risk for invasive aspergillosis. Here, we highlight recent developments in the understanding of ROS at the interface of the dynamic A. fumigatus-host interaction.

Susceptibility Testing of Environmental and Clinical Aspergillus sydowii Demonstrates Potent Activity of Various Antifungals.

The genus Aspergillus consists of a vast number of medically and environmentally relevant species. Aspergillus species classified in series Versicolores are ubiquitous in the environment and include the opportunistic pathogen Aspergillus sydowii, which is associated with onychomycosis and superficial skin infections. Despite frequent clinical reports of A. sydowii and related series Versicolores species, antifungal susceptibility data are scarce, hampering optimal treatment choices and subsequent patient outcomes. Here, we employed antifungal susceptibility testing (AFST) based on microbroth dilution on a set of 155 series Versicolores strains using the common antifungals amphotericin B, itraconazole, voriconazole, posaconazole, isavuconazole and micafungin with the addition of luliconazole and olorofim. All strains were identified using partial calmodulin gene sequencing, with 145 being A. sydowii, seven A. creber and three A. versicolor, using the latest taxonomic insights. Overall, tested antifungals were potent against the entire strain collection. In comparison to A. fumigatus, azole and amphotericin B MICs were slightly elevated for some strains. AFST with luliconazole and olorofim, here reported for the first time, displayed the highest in vitro activity, making these antifungals interesting alternative drugs but clinical studies are warranted for future therapeutic use.

Brilacidin, a host defense peptide mimetic, potentiates ibrexafungerp antifungal activity against the human pathogenic fungus Aspergillus fumigatus.

Aspergillus fumigatus is the primary etiological agent of aspergillosis. Here, we show that the host defense peptide mimetic brilacidin (BRI) can potentiate ibrexafungerp (IBX) against clinical isolates of A. fumigatus. BRI + IBX can inhibit the growth of A. fumigatus voriconazole- and caspofungin-resistant clinical isolates. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against viruses, bacteria, and fungi. In vitro, combination of BRI + IBX plays a fungicidal role, increases the fungal cell permeability, decreases the fungal survival in the presence of A549 epithelial cells, and appears as a promising antifungal therapeutic alternative against A. fumigatus. IMPORTANCE: Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Aspergillus fumigatus causes a series of distinct invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. A. fumigatus causes a spectrum of distinct clinical entities named aspergillosis, which the most severe form is the invasive pulmonary aspergillosis. There are few therapeutic options for treating aspergillosis and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a synergizer o fibrexafungerp (IBX) against A. fumigatus. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. We propose the combination of BRI and IBX as a new antifungal combinatorial treatment against aspergillosis.

Number of sinus procedures reduces inpatient mortality for invasive fungal rhinosinusitis.

OBJECTIVES: To evaluate surgical outcomes of invasive fungal rhinosinusitis MATERIALS AND METHODS: The National Inpatient Sample Database (2000-2015 Q3) was queried for patients with a diagnosis of aspergillosis and/or mucormycosis and a diagnosis of acute sinusitis using the International Classification of Diseases, Ninth Edition. Factors associated with inpatient mortality were then identified with multivariate logistic regression. RESULTS: 514 adult patients with a median age of 57.0 years were identified, of which 231 (44.9 %) underwent sinus surgery. Surgical patients had a longer length of stay (17.0 vs 9.0 days, p < 0.001) and higher total charges ($139,762.00 vs $57,945.00, p < 0.001). The number of sinus procedures was associated with reduced odds of inpatient mortality (OR 0.69; p < 0.001) in multivariate analysis. Hypertension (OR 0.34, p = 0.002) and chronic kidney disease (OR 0.23, p = 0.034) were associated with reduced odds of inpatient mortality. Total number of procedures (OR 1.24; p = 0.002), mucormycosis (OR 2.75, p = 0.002), age (OR 1.03, p = 0.006) and acid-base disorders (OR 2.85, p = 0.012) were associated with increased odds of inpatient mortality. CONCLUSION: This represents the first large scale study to evaluate outcomes for invasive fungal rhinosinusitis. These findings suggest the odds of inpatient mortality decrease with greater extent of sinus surgery performed. The potentially protective roles of hypertension and chronic kidney disease should be evaluated in future research.

Platelet-derived biomaterial controls aspergillus fumigatus keratitis by decreasing fungal burden: an in vivo study.

Fungal keratitis is a severe corneal infection characterized by suppurative and ulcerative lesions. Aspergillus fumigatus is a common cause of fungal keratitis. Antifungal drugs, such as natamycin, are currently the first-line treatment for fungal keratitis, but their ineffectiveness leads to blindness and perforation. Additionally, the development of fungal resistance makes treating fungal keratitis significantly more challenging. The present study used platelet-derived biomaterial (PDB) to manage A. fumigatus keratitis in the animal model. Freezing and thawing processes were used to prepare PDB, and then A. fumigatus keratitis was induced in the mice. Topical administration of PDB, natamycin, and plasma was performed; quantitative real-time PCR (qPCR) and histopathologic examination (HE) were used to assess the inhibitory effect of the mentioned compounds against fungal keratitis. The qPCR results showed that PDB significantly decreased the count of A. fumigatus compared to the control group (P-value ≤ 5). Natamycin also remarkably reduced the count of fungi in comparison to the untreated animal, but its inhibitory effect was not better than PDB (P-value > 5). The findings of HE also demonstrated that treatment with PDB and natamycin decreased the fungal loads in the corneal tissue. However, plasma did not show a significant inhibitory effect against A. fumigatus. PDB is intrinsically safe and free of any infections or allergic responses; additionally, this compound has a potential role in decreasing the burden of A. fumigatus and treating fungal keratitis. Therefore, scientists should consider PDB an applicable approach to managing fungal keratitis and an alternative to conventional antifungal agents.

SUBA-itraconazole in the treatment of systemic fungal infections.

Conventional itraconazole (c-ITZ) can be used for a variety of fungal infections although variable absorption has been a significant limitation. Super-bioavailable itraconazole (SUBA-ITZ) is a novel formulation that overcomes absorption concerns by utilizing a polymer-matrix to disperse active drug and facilitate dissolution. The pH-driven matrix allows concurrent proton pump inhibitor administration without significant effects on drug concentrations. The enhanced bioavailability of SUBA-ITZ allows for lower dosing, while achieving similar serum concentrations as c-ITZ and SUBA-ITZ is now US FDA approved in the treatment of blastomycosis, histoplasmosis and aspergillosis. Common side effects of SUBA-ITZ include gastrointestinal disorders, peripheral edema and drug-induced hypertension. Given the significant differences in pharmacokinetics between the formulations, c-ITZ and SUBA-ITZ capsules are not considered interchangeable. It is important to note that drug errors may occur when transitioning a patient from one formulation to another.

Itraconazole is an antifungal agent used in the treatment of a number of mycoses. Prior formulations (versions) of itraconazole required strict dietary requirements and often had poor absorption. A new itraconazole formulation has since been developed ­ super bioavailable itraconazole (SUBA-itraconazole). This has no food requirements, has superior absorption and maintains effectiveness against a number of fungal infections.

Chelerythrine ameliorates Aspergillus fumigatus keratitis through suppressing the LOX-1/p38 MAPK signaling pathway.

PURPOSE: Aspergillus fumigatus (A. fumigatus) keratitis is a type of infectious corneal disease that significantly impairs vision. The objective of this study is to evaluate the therapeutic potential of chelerythrine (CHE) on A. fumigatus keratitis. METHODS: The antifungal activity of CHE was assessed through various tests including the minimum inhibitory concentration test, scanning electron microscopy, transmission electron microscopy, propidium iodide uptake test and plate count. Neutrophil infiltration and activity were assessed using immunofluorescence staining and the myeloperoxidase test. RT-PCR, western blotting assay, and ELISA were performed to measure the expression levels of proinflammatory cytokines (IL-1ß and IL-6), NF-E2-related factor (Nrf2), heme oxygenase-1 (HO-1), and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), as well as to determine the ratio of phosphorylated-p38 (p-p38) mitogen-activated protein kinase (MAPK) to p38 MAPK. RESULTS: In vitro, CHE inhibited the growth of A. fumigatus conidia, reduced fungal hyphae survival, and prevented fungal biofilm formation. In vivo, CHE reduced the severity of A. fumigatus keratitis and exhibited an excellent anti-inflammatory effect by blocking neutrophil infiltration. Furthermore, CHE decreased the expression levels of proinflammatory cytokines and LOX-1 at both mRNA and protein levels, while also decreasing the p-p38 MAPK/p38 MAPK ratio. Additionally, CHE increased the expression levels of Nrf2 and HO-1. CONCLUSION: CHE provides protection against A. fumigatus keratitis through multiple mechanisms, including reducing fungal survival, inducing anti-inflammatory effects, enhancing Nrf2 and HO-1 expression, and suppressing the signaling pathway of LOX-1/p38 MAPK.

[Diagnosis of peripheral cavitary squamous cell lung carcinoma with Aspergillus infection using LungPro navigation system: a case report].

Virtual bronchoscopic navigation (VBN) is increasingly being used to diagnose peripheral lung lesions, allowing precise guidance of the bronchoscope to the target lesions, thereby improving diagnostic accuracy. This paper reported a patient admitted due to hemoptysis, with an initial clinical diagnosis of squamous cell lung carcinoma with brain and bone metastases. Previous attempts had failed to obtain tissue samples from the lung lesions. Upon admission, the LungPro navigation system was used to perform a bronchoscopic transparenchymal nodule access (BTPNA). Pathological examination of the lung tissue and microbiological analysis of bronchoalveolar lavage fluid confirmed the diagnosis of peripheral cavitary squamous cell lung carcinoma with Aspergillus infection. Following antifungal and antineoplastic treatment, the patient's symptoms improved markedly and she was subsequently discharged.

Clinicopathological study of otomycosis in a tertiary hospital in South-west Nigeria.

Background: Otomycosis is common in environments with hot, humid weather, and it may be challenging to manage. Objectives: To profile common clinical presentations, the pathogenic fungi, the treatment modalities with responses, and explore clinical factors associated with having positive fungal culture in Otomycosis. Methods: Retrospective review of patients with Otomycosis. Demographic and clinical parameters, otoscopic findings and mycological study results were recorded. The treatment modalities used and treatment response were summarized. Comparative statistical analyses of associated factors to positive fungal culture were performed with Chi square test, and Student's t-test, using SPSS version 22.0. Results: Total of 71 patients with M: F=1:1.8, mean age 38.5±19.8 years. Average duration of symptoms was 5.4 ±4.6 weeks; common presenting complaint was itchy ear (33.8%). Majority of patients (85.9%) had unilateral ear involvement, 50.0% applied ototopic medications before presentation, 8.5% had multiple co-morbidities. 20 patients had positive fungal culture results; common fungal isolate was Aspergillus niger 9 (45.0%).Clinical factors associated with positive culture of fungus were age, non-previous use of ototopic drugs, and presence of co-morbidity. The most common treatment was local ear debridement and use of topical antifungal creams. Majority (91.5%) of the patients responded with resolution of fungal infection. Complications rate was 8.4%. Conclusions: Otomycosis commonly present with itchy ears, the pathogenic fungi commonly being Aspergillus species. The factors associated with positive fungal culture were age, non-usage of ototopic agents and presence of co-morbidity. Treatment modality used was local debridement and topical antifungal agents, which produced favourable response in most patients.

Is there still a place for serum galactomannan in the diagnosis of invasive aspergillosis in children at high risk and under antifungal prophylaxis?

BACKGROUND: The performance of serum galactomannan (GM) for the diagnosis of invasive aspergillosis (IA) has been studied mainly in adults. Paediatric data are scarce and based on small and heterogeneous cohorts. OBJECTIVE: To evaluate the performance of serum GM for the diagnosis of IA in a paediatric oncologic population at high risk of IA and to clarify the impact of antifungal prophylaxis on this test. METHODS: We performed a retrospective study from January 2014 to December 2020 in the paediatric oncologic haematologic department of the University Hospital of Bordeaux. The diagnosis of IA was made using the recommendations of the EORTC and the MSGERC. RESULTS: Among the 329 periods at high risk of IA in 222 patients, the prevalence of IA was 1.8% (3 proven and 3 probable IA). In the total population, the sensitivity, and the positive predictive value (PPV) were respectively 50% and 17.6%. Under antifungal prophylaxis, the sensitivity and PPV dropped, respectively, to 33.3% and 14.3%. In this group, the post-test probability of IA was 2% for a negative serum GM and only 14%. CONCLUSION: In this large cohort of children at high risk of IA, the incidence of IA is low and the diagnostic performance of GM is poor, especially in the case of mould-active prophylaxis. Screening should be targeted rather than systematic and should be reserved for patients at highest risk for IA without mould-active prophylaxis. Combination with other tests such as Aspergillus PCR would increase the accuracy of GM in screening setting.