Optical Density Index Research Articles

Identifying Gaps in the International Consensus Case Definitions for Invasive Aspergillosis: A Review of Clinical Cases Not Meeting These Definitions.

International consensus definitions for invasive aspergillosis (IA) in research are rigorous, yet clinically significant cases are often excluded from clinical studies for not meeting proven/probable IA case definitions. To better understand reasons for the failure to meet criteria for proven/probable infection, we herein review 47 such cases for their clinical and microbiological characteristics and outcomes. Data on 47 cases that did not meet consensus IA definitions but were deemed significant were derived from a retrospective, observational, multicenter survey of 382 presumed IA cases across Australasia, of which findings of 221 proven/probable infections were recently published. The clinical, microbiological, and radiologic characteristics of these cases were analyzed. Mortality outcomes were compared with those of 221 proven/probable cases. Of 47 cases studied, 15 lacked classical host factors; 22 exhibited only a single positive Aspergillus polymerase chain reaction result; 7 lacked typical IA radiologic findings on chest computed tomography; and 3 had borderline galactomannan optical density indices (<1.0 but ≥0.5) in bronchoalveolar lavage fluid. The median age of patients was 61 years (IQR, 52-68); 34 were male (72%). Seven patients (15%) required intensive care admission. All patients had lung as the primary site of infection. Antifungal treatment was initiated in 42 patients (89%). All-cause 90-day mortality was 33%, similar to the 30% mortality in the comparative cohort (n = 221). Our findings highlight the limitations of current consensus definitions for IA. Notably, the mortality of patients not meeting these definitions was similar to that of patients with proven/probable IA. Further studies, especially of patients with a single positive Aspergillus polymerase chain reaction result and those without host factors, are needed to determine if future consensus definitions may benefit from modifications.

IgG reactivity to different desmoglein-3 ectodomains in pemphigus vulgaris: novel panels for assessing disease severity.

Pemphigus vulgaris (PV) is an autoimmune disease characterized by IgG autoantibodies targeting desmoglein-3 (Dsg3), leading to blistering of mucous membranes and skin. Although commercial ELISA kits effectively diagnose PV, correlation with clinical phenotype remains unclear. This study assesses multiple panels for monitoring disease severity and activity by profiling IgG autoantibodies against Dsg3's various extracellular ectodomains. We designed and expressed different extracellular domains of Dsg3 in HEK293T cell line and developed 15 different ELISA panels, each using a single or multi ectodomains encompassing the entire extracellular region of Dsg3 to detect specific autoantibodies against the particular part of Dsg3. To validate our approach, we compared our ELISA panel for the full Dsg3 (EC1-5) against a commercial kit using 154 random serum samples from PV patients, demonstrating a strong correlation. For evaluation of IgG autoantibody profiles in our panels, 59 PV patients were included, along with 11 bullous pemphigoid patients, and 49 healthy controls. For all the included subjects, 15 predefined ELISA panels were tested. The IgG autoantibodies against EC1 were detected in 86% of patients with a positive full Dsg3 ectodomain (EC1-5) ELISA, with 26% against EC2, 14% for EC3, 29% for EC4, and 23% for EC5. Among the panels with multiple Dsg3 ectodomains, EC1-3 and EC1-4 were representative of the entire Dsg3 ectodomain in terms of ELISA positivity across all included patients. A significant correlation (P<0.05) was observed between ELISA optical density (OD) and Pemphigus Disease Area Index (PDAI) scores in five panels, EC1, EC2-3, EC2-5, and EC3-4 in addition to the full ectodomain. It suggests an association with disease severity. Interestingly, while the ELISA panel for the entire Dsg3 extracellular ectodomains did not differentiate disease phases, in three of our panels, including EC1, EC3-5, and EC2-5, ANOVA analysis showed a statistically significant difference between the groups of patients in remission, partial remission or persistent lesions, and those with active disease (new cases or relapse). Among these three panels, EC1 was the only one that showed a significant difference in the multiple comparisons analysis; patients in the active phase had higher levels of autoantibodies than those in 'partial remission or persistent lesions' and 'complete remission' groups. The level of autoantibodies against EC1 was not only correlated with the full ectodomain but also associated with higher disease severity and active disease phase. This study indicates that a detailed autoantibody profile against Dsg3 ectodomains could serve as a marker for PV severity and activity which may potentially enhance early treatment initiation.

Clinical and morphological features of lung injury long-term after SARS-CoV-2 recovery

To study the clinical and histological profile of lung tissue in patients with persistent pulmonary disease, respiratory symptoms and CT findings after SARS-CoV-2 infection. The study included 15 patients (7 females and 8 males) with a mean age of 57.7 years. All patients underwent laboratory tests, chest computed tomography, echocardiography, and pulmonary function tests. Pulmonary tissue and bronchoalveolar lavage samples were obtained by fibrobronchoscopy, transbronchial forceps (2 patients), and lung cryobiopsy (11 patients); open biopsy was performed in 2 patients. Cellular composition, herpesvirus DNA, SARS-CoV-2, Mycobacterium tuberculosis complex, galactomannan optical density index, and bacterial and fungal microflora growth were determined in bronchoalveolar lavage. SARS-CoV-2 was also identified in samples from the nasal mucosa, throat and feces using a polymerase chain reaction. The results showed no true pulmonary fibrosis in patients recovered from SARS-CoV-2 infection with persistent respiratory symptoms, functional impairment, and CT findings after SARS-CoV-2 infection. The observed changes comply with the current and/or resolving infection and inflammatory process. Thus, no true pulmonary fibrosis was found in patients after SARS-CoV-2 infection with persistent respiratory symptoms, functional impairment, and CT findings. The observed changes comply with the current and/or resolving infection and inflammatory process.

EXAMINATION OF GALACTOMANNAN LEVELS IN INTRAOCULAR FLUID TO ASSIST THE DIAGNOSIS OF ASPERGILLUS ENDOPHTHALMITIS.

To evaluate the utility of galactomannan testing of intraocular fluid in the diagnosis of Aspergillus endophthalmitis (AE). This retrospective study enrolled three groups of patients, including those with 17 eyes with AE; 20 eyes with intraocular infection of bacteria, viruses, or other fungi; and 19 eyes with cataract. Intraocular fluid from all these patients was collected for galactomannan testing. In addition, the receiver operating characteristic curves and diagnostic significance were analyzed. The mean optical density index (ODI) of galactomannan was 5.77 ± 1.73 in the AE group, which was significantly higher than that in the non- Aspergillus intraocular infection group (0.19 ± 0.11, P < 0.001) and the negative control group (0.29 ± 0.27, P < 0.001). The area under the receiver operating characteristic curve (area under the curve) was 1.00 (95% confidence interval, 1.00-1.00; P < 0.001) in the AE group and the other two groups. At a cutoff optical density index of 1.88, the sensitivity and specificity were 100.0% and 100.0%, respectively, and the Youden index reached its highest value of 1.00. Galactomannan testing of intraocular fluid indicated good sensitivity and specificity for the diagnosis of AE, thereby promising a rapid diagnostic modality for AE.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Burning characteristics of power cables with cone calorimeter

Power cables consist of insulation, padding and sheathing, which are highly susceptible to ignition. Power cables are an important factor affecting fire risk in urban utility tunnels (UUTs). In this paper, the combustion characteristics of four types of power cables (YJV, ZR-YJV, ZR-VV, and ZR-PE) in UUTs were investigated using a cone calorimeter. In this paper, laboratory experiments were conducted to investigate the combustion characteristics of power cables with two different parameters including two heat fluxes (35 kW/m2 and 75 kW/m2) and two sheath thicknesses (3 mm and 5 mm). The effects of heat release rate (HRR), effective heat combustion (EHC), optical density index (ODI) and smoke production rate (SPR) on ignition and combustion were investigated. The results showed that ZR-VV power cables have lower TTI, lower average HRR, lower EHC, higher MLR, and lower SEA than YJV and ZR-YJV power cables.With a conical calorimeter and heat flux of 35 kW/m2, the HRR of the power cables increased within 200 s, while for ODI, the total smoke output of ZR-YJV cables was minimized. Heat flux has a significant effect on HRR, SPR and EHC of ZR-PE cable. Sheath thickness has little effect on HRR, SPR and EHC of ZR-PE cables. In addition, one of the most important parameters, the ignition time, which depends on the composition and structure of the cable, was identified. Finally, the effect of external heat flux is complex and depends on the combustion characteristics of the power cable. Laboratory tests provide useful information for understanding the combustion behavior of power cables, including heat release rate, effective thermal burn, optical density index, and smoke production.

Near IR light sensitization modulated to self-assembled CuO–CuxS nanorods thin films

An assembled CuO-CuxS nanorods heterostructure has been produced by liquid chemical conversion and wet etching of the Cu thin film. The chemical etching and anionic exchange modify and convert the Cu thin film to self-assembled CuO/CuxS random nanorods. The enhanced near infrared (NIR) light absorption capability and the effective separation of electron–hole pairs generated by the conjugated CuO-CuxS nanorods complement high visible (especially red) light driven photocatalytic activities as well as NIR photodetecting performances.The surface morphology, chemical content, crystalline analysis and structural vibrations of the CuO/CuxS nanorods were characterized using field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and Raman scattering, respectively. Diffuse reflectance spectroscopy was utilized to evaluate optical properties of the CuO-CuxS nanorods. The assembled CuO–CuxS nanorods thin film exhibits good crystallinity with superior reproducibility and high selectivity for NIR absorption. The CuxS coupling into CuO is also responsible to surface enhanced Raman scattering. The static and high frequency dielectric constant, Urbach tail, optical carrier density and nonlinear refractive index have been estimated. The bandgap energy and optical carrier density are estimated around 1.22 eV and 1027 m−3, respectively. The photoharvesting performance was characterized using under sunlight illumination, and green, red and NIR laser irradiation. The CuO–CuxS hetero-interface manipulate charge transferring of the photoinduced carriers, which promotes the photodegradation efficiency of Methylene blue (MB) and NIR photosensitization.

FEATURES OF COL1A1 EXPRESSION IN BREAST CANCER TISSUE OF YOUNG PATIENTS.

In the last decades, the incidence of breast cancer (BCa) in young women has been increasing steadily. The quantitative indicators of expression of collagen, which play important role in stromal microenvironment, and their association with the age and survival rates of BCa patients have not been yet definitively clarified. To investigate the relationship between the COL1A1 gene expression at the mRNA and protein levels in BCa tissue and the clinicopatological features and survival rates of BCa patients of different age groups. The study was conducted on the clinical material of 50 patients with stage I-III BCa. COL1A1 gene expression at the mRNA and protein levels in BCa tissue were studied using the real-time PCR and immunohistochemical methods, as well as the bioinformatic analysis (UALCAN and Kaplan - Meier Plotter databases). The bioinformatic analysis showed that BCa tissue is characterized by 6.0 times (p < 0.05) higher level of COL1A1 mRNA compared to normal breast tissue. The correlation of COL1A1 expression at the mRNA and protein levels with the molecular subtype of neoplasms was demonstrated. According to Kaplan - Meier Plotter database, a low level of expression of COL1A1 protein level in BCa tissue is associated with lower rates of relapse-free survival of patients. The ex vivo study of the clinical material revealed a decrease in COL1A1 protein expression in tumor tissue of young patients with BCa of T3 category (p < 0.0374), low differentiation grade (p < 0.0163) and basal molecular subtype (p < 0.0001). A correlation between the expression of COL1A1 at the mRNA and protein levels and the expression status of estrogen receptors (p < 0.0001) and progesterone receptors (p < 0.0040) was established. The relapse-free 3-year survival rate of young BCa patients is significantly lower in the presence of a low COL1A1 optical density index in the tumor tissue. The identified relationship between COL1A1 expression and such indicators of BCa malignancy as tumor size, differentiation grade, molecular subtype, receptor status, and the recurrencefree survival of patients indicates the prospects of its use to predict the aggressiveness of the BCa course in young patients.

Metagenomic next-generation sequencing for detecting Aspergillosis pneumonia in immunocompromised patients: a retrospective study.

The identification of Aspergillus by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of this study was to determine whether mNGS could provide an accurate and efficient method for detecting invasive pulmonary aspergillosis (IPA) in immunocompromised patients (ICP). A total of 133 ICP admitted to the ICU between January 2020 and September 2022 were enrolled in the study, of which 46 were diagnosed with IPA and 87 were non-IPA cases. The bronchoalveolar lavage fluid (BALF) was analyzed for the presence of Aspergillosis and other co-pathogens using mNGS, and its diagnostic performance was compared to conventional microbial tests (CMTs) that included smear, cultures, serum and BALF galactomannan (GM) test. Clinical composite diagnosis was used as the reference standard. mNGS had a sensitivity, specificity, and accuracy of 82.6%, 97.7%, and 92.5%, respectively, in diagnosing IPA. These findings were comparable to those of the combination of multiple CMTs. Interestingly, the sensitivity of mNGS was superior to that of any single CMT method, as demonstrated by comparisons with smears (8.7%, P < 0.001), culture (39.1%, P < 0.001), serum GM (23.9%, P < 0.001) and BALF GM (69.6%, P = 0.031). mNGS was capable of accurately distinguish strains of Aspergillus genus, with a consistency of 77.8% with culture. Furthermore, mNGS also identified A. fumigatus, A. flavus, A. terrestris, A. oryzae and Mucor spp. in culture-negative cases. The sequencing reads of Aspergillus by mNGS exhibited extensive variation, ranging from 11 to1702. A positive correlation was observed between the optical density index of BALF GM and unique reads by mNGS (r = 0.607, P = 0.001) in BALF-GM positive patients. Notably, mNGS was able to diagnose 35 out of 37 cases with mixed infection, with P. jirovecii and cytomegalovirus being the most common co-pathogens. mNGS presents a feasible and remarkably sensitive approach for detecting Aspergillus in ICP, thereby serving as a valuable adjunctive tool to CMT. Furthermore, mNGS's ability to accurately identify fungal species and co-pathogens can assist in guiding appropriate antimicrobial therapy.

Optical gas sensing and kinetics of azobenzene modified niobium metal-organic framework film composite optical waveguides

A niobium metal-organic framework (Nb-MOF) film with graphene-like structure fabricated on lithium niobate (LiNbO3) film composite optical waveguides1 (COWG) substrate, then modified by embedding azobenzene2 (AZB) using UV-light irradiation approach. The characteristics, including structure, morphology, gas sensitivity and kinetics were studied. After modifying, film morphology evolves to an ant-nest structure, which resulted in a flatter surface, smaller pores, higher optical density and refractive index. In dynamic gas sensing test (at 298 K, 0.92 atm), [email protected] film COWG uniquely responded to H2S coexisting with the same concentration (10 ppm) of benzenes and amines. The proton transfer and Lewis acid-base interactions were dominant during H2S gas adsorption. A spatial hindrance to proton transfer results a lower sensitivity of [email protected] film COWG than that of Nb-MOF film COWGs. H2S gas adsorption kinetics followed the pseudo-second order (PSO)3 model, the adsorption capacity (qe) on per unit surface exhibits a medium value of 77.34 ng·cm−2 at 298 K.

The Use of Galactomannan Antigen Assays for the Diagnosis of Invasive Pulmonary Aspergillosis in the Hematological Patient: A Systematic Review and Meta-Analysis

The optimal cut-off value of the optical density index of the galactomannan antigen assays (GM) for diagnosing invasive pulmonary aspergillosis in hematological patients is a disputed topic. This article conducts a systematic review with a meta-analysis to establish which optical density index (ODI) cut-off value should be implemented into clinical practice. Pubmed, Embase and Cochrane databases were searched (N = 27). The pooled data, using a generalized linear mixed model with binomial distribution, resulted in an overall serum sensitivity of 0.76 and a specificity of 0.92. For serum ODI 0.5 there was a pooled sensitivity of 0.92 and a specificity of 0.84. The pooled data of all broncho-alveolar lavage (BAL) studies resulted in an overall sensitivity of 0.80 and a specificity of 0.95. For BAL ODI 0.5, there was a pooled sensitivity of 0.75 and a specificity of 0.88. For the BAL ODI 1.0 pooling, the studies resulted in a sensitivity of 0.75 and a specificity of 0.96. Serum ODI of 0.5 and BAL ODI of 1.0 are the most suitable cut-offs for clinical practice. However, our study affirms that the evidence for the use of GM in clinical practice for the hematological malignancy patient is currently insufficient and more research is needed to determine the diagnostic value of GM.

Retrospective Multicenter Evaluation of the VirClia Galactomannan Antigen Assay for the Diagnosis of Pulmonary Aspergillosis with Bronchoalveolar Lavage Fluid Samples from Patients with Hematological Disease.

Galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid samples has become an essential tool to diagnose invasive pulmonary aspergillosis (IPA) and is part of diagnostic guidelines. Enzyme-linked immunosorbent assays (ELISAs) (enzyme immunoassays [EIAs]) are commonly used, but they have a long turnaround time. In this study, we evaluated the performance of an automated chemiluminescence immunoassay (CLIA) with BAL fluid samples. This was a multicenter retrospective study in the Netherlands and Belgium. BAL fluid samples were collected from patients with underlying hematological diseases with a suspected invasive fungal infection. Diagnosis of IPA was based on the 2020 European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) consensus definitions. GM results were reported as optical density index (ODI) values. ODI cutoff values for positive results that were evaluated were 0.5, 0.8, and 1.0 for the EIA and 0.16, 0.18, and 0.20 for the CLIA. Probable IPA cases were compared with two control groups, one with no evidence of IPA and another with no IPA or possible IPA. Qualitative agreement was analyzed using Cohen's κ, and quantitative agreement was analyzed by Spearman's correlation. We analyzed 141 BAL fluid samples from 141 patients; 66 patients (47%) had probable IPA, and 56 cases remained probable IPA when the EIA GM result was excluded as a criterion, because they also had positive culture and/or duplicate positive PCR results. Sixty-three patients (45%) had possible IPA and 12 (8%) had no IPA. The sensitivity and specificity of the two tests were quite comparable, and the overall qualitative agreement between EIA and CLIA results was 81 to 89%. The correlation of the actual CLIA and EIA values was strong at 0.72 (95% confidence interval, 0.63 to 0.80). CLIA has similar performance, compared to the gold-standard EIA, with the benefits of faster turnaround because batching is not required. Therefore, CLIA can be used as an alternative GM assay for BAL fluid samples.

Effect of a Tetraethoxysilane Hydrolysis Reaction Catalyst on the Precipitation of Hydrolysis Products in the Pores of a Polyimide Track Membrane

This paper presents the results of obtaining a composite film based on polyimide track membranes filled with a silica filler, although the issue of the deposition of this filler in the pores of the given membranes remained unexplored. The filler was obtained by hydrolysis of tetraethoxysilane using an alkaline and acid catalyst. This paper presents the results of the effect of the tetraethoxysilane hydrolysis reaction catalyst on the precipitation of hydrolysis products in the pores of the polyimide track membrane. The factors influencing the formation of silicon oxide nanofibers within the matrix template (polyimide track membrane) are determined. It was found that the use of an acid catalyst provides the highest rates of filling, while when using an alkaline catalyst, the filling is practically not observed, and only single pores are filled. The properties of the composite film obtained were investigated. SEM images of the surface and chip of the composite while using alkaline and acid catalyst are presented. The spatial structure of composite films based on track membranes was investigated by FTIR spectroscopy. The hydrolysis of tetraethoxysilane in an acid medium significantly decreases the optical density index of the membranes and simultaneously increases their light transmission index. The greatest changes are observed in the range of 500–1000 nm, and there are no detectable changes in the range of 340–500 nm. When using an alkaline catalyst, there is not the same significant decrease in the relative optical density index D.

Interaction of Cyprinus carpio Linnaeus with the biofilm-forming Aeromonas hydrophila.

The resistance of susceptible fish populations and the adaptive potential of heterogeneous biofilms, which cause multiple antibacterial resistance and long-term persistence of microorganisms, mediate the development and outcome of the infectious process. The study of the fish immunological parameters in interaction with biofilm-forming bacteria is of practical importance for assessing the stability of the homeostasis of the fish. This study aimed to determine the immunobiological parameters of Cyprinus carpio Linnaeus when interacting with biofilm-forming bacteria Aeromonas hydrophila. Clinically healthy fish C. carpio L. (Linnaeus, 1758) of both sexes, aged 4 years, and weighing 1.0-1.5 kg (n = 10), were used in this study. The fish were taken from the pond of the VNIIR experimental base in the period of 2020-2022. The standard method was employed to determine the phagocytic activity of blood cells, the total redox activity of neutrophils, and the bactericidal activity of blood serum. After 24-48 h of cultivation in nutrient broth, the implementation of the processes of intercellular communication of bacteria had common patterns of formation of the heterogeneous structure of biofilms. Moreover, analyzing the optical density indices (density, D), it was observed that A. hydrophila was a strong producer of biofilms, as the optical density of the sample (density of sample, Ds) exceeded the optical density of the control (density of control, Dc) by more than 4 times (D = 0.464 ± 0.07). The ratio of the average number of microorganisms attached to the surface of one erythrocyte (average adhesion index) and the percentage (%) of erythrocytes having bacteria on their surface (adhesion coefficient [AC]) was 14.05 ± 0.72, and the adhesion index, AI was ≥4.00, indicating A. hydrophila to be highly adhesive. In addition, the AC of erythrocytes having bacteria on the surface was 14.05% ± 0.72%. A direct correlation was established (R2 = 0.94) between the AC (14.05% ± 0.11%-13.29% ± 0.08%) and the phagocytic index (11.3% ± 0.29%-32.0% ± 0.8%). The indicators of spontaneous nitro blue tetrazolium were 103.20 ± 11.70 when estimating the total redox activity of neutrophils. The optical density increased to 182.10 ± 21.12 with the addition of 20.0 mL of A. hydrophila bacteria (1 billion/mL) and the activity of neutrophils also increased. Among the markers of homeostasis stability, immunological indicators most fully reflect the mechanisms of initiation, development, and outcome of the infectious process mediated by the interaction of adhesive molecules of multicellular eukaryotes and adhesives of infectious disease pathogens. The research will contribute to further understanding the potential mechanism of quorum-sensing molecules and the search for new anti-adhesive drugs that reduce the formation of biofilms.

P170 Life threatening hemoptysis in COVID-19 associated Pulmonary Aspergillosis (CAPA)

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectiveWe report a case of large pulmonary mycotic aneurysms with massive hemorrhage as an unusual complication of CAPA which required vascular radiological interventions along with appropriate antifungal treatment.Method and ResultsA 71-year-old female patient had COVID-19 and was admitted elsewhere and she received steroids, aspirin, antibiotics, and fluconazole. Cough, dyspnea, and hemoptysis started 3 weeks later which markedly worsened over 4 days, requiring emergency hospitalization due to shock, and she received a large number of packed RBCs. The chest CT scan revealed two large nodular opacities with central breakdown and CT pulmonary angiography revealed large mycotic aneurysms within the nodular opacities (Fig. 1).The important task at the moment of presentation was pulmonary artery embolization to arrest hemoptysis; which took precedence over the diagnosis and treatment of the likely infectious process. Both aneurysms were embolized using coils and vascular plugs resulting in their obliteration.Common causes of such nodules with central necrotic cavitation and formation of pseudoaneurysms are angioinvasive molds like Aspergillus and Mucorales. In the post-COVID-19 and post steroid setting in India, invasive Mucormycosis (IM) is thought to be more common than invasive Aspergillosis (IA). A mixed infection with these molds appears to be present in about 15% of the cases. Absence of DM or hyperglycemia was somewhat against a diagnosis of Mucormycosis. TB was considered less likely due to the imaging features and Nocardia was considered less likely due to the tempo of the illness and the severity of hemoptysis.Since the clinical distinction between Aspergillosis and Mucormycosis was not possible and posaconazole can be potentially useful for both, it was chosen for treatment in preference to voriconazole. Both amphotericin B and isavuconazole were in short supply at that time. Posaconazole was used for the patient intravenously followed by gastroresistant tablets. Expectorated sputum revealed narrow, septate, acute angle branching fungal hyphae. Therapeutic drug monitoring was used later to assure an adequate drug exposure. Serum galactomannan and BDG reports were received soon after and were 2.49 ODI (Optical density Index) and >523pg/ml respectively. The mold grew in culture as shown in and was identified by morphological features and by MALDI TOF MS as Aspergillus fumigatus (Fig. 2). Sensititre MIC to posaconazole was found to be 0.12 which is considered in the susceptible range.Despite these findings indicating IA, posaconazole was not replaced by voriconazole as IM could not be ruled out as part of a mixed infection. The patient showed clinical improvement, had no further hemoptysis, serum galactomannan turned negative and CT showed obliteration of the aneurysms.ConclusionPosaconazole and isavuconazole may indeed emerge as good contemporary choices over voriconazole for IA and over amphotericin B for IM.This case adds to the clinical experience of using medical treatment with posaconazole as the sole drug and not undertaking surgery in cases such as these, due to certain extenuating circumstances.

P428 Evaluation of Galactomannan enzyme assay in non-hematological non-neutropenic ICU admitted patients for diagnosis of Invasive Pulmonary Aspergillosis as per EORTC criteria 2019

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectiveThe objective of this study was to evaluate galactomannan enzyme assay in non-hematological ICU patients for diagnosis of Invasive Pulmonary Aspergillosis as per EORTC criteria 2019.MethodsGalactomannan detection in serum samples was performed by enzyme-linked immunosorbent assay in 138 patients with clinically suspected pulmonary aspergillosis between January 2012 and January 2019 in patients admitted to ICUs. Patients with hematological diseases or who underwent HSCT were excluded. Control group (n = 25) was selected from patients with no obvious immunosuppression, cough/dyspnea, or any other respiratory symptoms, etc admitted for elective surgeries from surgery wards. According to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group revised in 2019, the patients were categorized as proven, probable, and possible IA. Galactomannan optical density indices ≥0.5 and ≥1 were analyzed with respect to clinical, radiological, and mycological evidence.ResultsAmongst 138 patients 2 fulfilled the criteria of proven IA, 78 were probable IA, and the rest (58) were grouped under possible IA. In the control group, the Galactomannan optical density index was ≤ 0.5. Receiver operating characteristic curve analysis showed the serum GM detection cutoff value was 0.91 (95% CI 0.885-0.973, P-value <.0001) with Youden index J = 0.78, its diagnostic value for pulmonary aspergillosis was optimized, and the sensitivity and specificity reached 83.75% and 94.83% respectively. Other cutoffs had high variance between sensitivity and specificity for the diagnosis of IPA.ConclusionOur study highlights the usefulness of the serum GM antigen test in the early diagnosis of IA and suggests a GMI cutoff of 0.91 as it has the highest diagnostic accuracy. Also, we recommend that patients with a GM OD of ≥1.0 should be labeled as clear GM positive, whereas those with <0.5 OD should be labeled as GM negative, and in those with OD ranging from 0.5 to 1.0, repeat sampling from the patient is advisable. It seems more reasonable not to overtreat all patients with fever refractory to broad-spectrum antibiotics with antifungal agents, but rather to decide taking into account the serum GM antigen positivity. A negative GM antigen can curtail the usage of unwarranted antifungal therapy, especially in resource-poor country like India.

Existing tests vs. novel non-invasive assays for detection of invasive aspergillosis in patients with respiratory diseases.

Background:Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays.Methods:Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed.Results:The entire cohort included 3530 admissions (proven/probable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven/probable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) (χ2 = 19.83, P < 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) (χ2 = 24.65, P < 0.001), and fungal culture (33% [84/253]) (χ2 = 29.38, P < 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher's exact P = 1.000) to and slightly lower specificity (87% [77/89]) (χ2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812–0.953]) and BAL GM (0.901 [0.824–0.977]) (P = 0.734). Sputum LFD had similar specificity (91% [81/89]) (χ2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) (χ2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) (χ2 = 6.95, P = 0.008), BDG (χ2 = 10.43, P = 0.001), and fungal culture (χ2 = 12.70, P < 0.001).Conclusions:Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.

Evaluation of Aspergillus Galactomannan Lateral Flow Assay on Serum and Bronchoalveolar Lavage Specimens

Background: Detection of biomarkers, such as galactomannan (GM), has proven to be of great significance in early recognition of invasive aspergillosis (IA). The aim of our study was to evaluate the lateral flow assay (LFA) for the detection of GM on serum and bronchoalveolar lavage (BAL) samples previously proven positive by enzyme-linked immunosorbent assay (ELISA). Methods: The study was performed on serum and BAL samples obtained from patients with suspected IA in the period from February 2019 to January 2020, which were previously GM positive by ELISA (Platelia Aspergillus Ag, Biorad, Hercules, USA). Samples were then tested by LFA (Aspergillus Galactomannan LFA, IMMY, Oklahoma, USA) with test line intensity visually read as 1+, 2+, 3+, or 4+. Results: A total of 45 GM ELISA positive serum and/or BAL samples were obtained from 41 patients; 25 (55,6 %) were BAL and 20 (44,4 %) serum samples. LFA showed a positive result in 39 out of 45 (86,7%) GM ELISA positive samples; 22/25 (88.0 %) BAL samples and 17/20 (85.0 %) serum samples tested positive. In BAL samples, low intensity test line of 1+ was significantly more frequent in GM ELISA positive samples with optical density index (ODI) &amp;lt; 1.0 (p=0.0002). Three serum samples with high GM ELISA ODI (&amp;gt;4.0) had low intensity line of 1+ when tested with LFA. Conclusions: Results obtained by LFA are comparable to GM ELISA. Since low intensity lines were found in serum samples with high ODI, this potentially makes BAL a superior sample for LFA, at least when visual and not automated reading is done.

A novel algorithm for diagnosis of invasive pulmonary aspergillosis based on pentraxin 3 gene polymorphisms and its adjusted value among autoimmune diseases patients.

BackgroundInvasive pulmonary aspergillosis (IPA) is a rapidly progressive and fatal disease for those with autoimmune diseases. The performance of existing diagnostic tools is unsatisfactory, and a novel algorithm based on pentraxin 3 (PTX3) gene polymorphisms with adjusted PTX3 and galactomannan (GM) values is urgently needed.MethodsLevels of PTX3 and GM were measured in the bronchoalveolar lavage fluid (BALF) and blood samples of patients who had autoimmune diseases with IPA between June 2017 and June 2021. Urea dilution was applied internally to correct the real BALF PTX3 and GM values. Three single-nucleotide polymorphisms (SNPs; rs1840680, rs2305619, and rs3816527) in the PTX3 gene were detected by polymerase chain reaction direct sequencing, and their associations with IPA were evaluated. Receiver operating characteristic (ROC) curves based on different variables were generated to determine the best algorithm for IPA diagnosis.ResultsThis study enrolled 50 patients with IPA and 100 without IPA in the control groups (comprising 50 patients with Aspergillus airway colonization and 50 patients with bacterial pneumonia). The levels of adjusted BALF PTX3 and GM were higher in the IPA group than in the control groups (P<0.05, respectively). For diagnosing IPA, the best adjusted cutoff value for PTX in BALF was 14.5 ng/mL and the best adjusted cutoff value for GM in BALF was 2.5 optical density index (ODI). The SNP rs1840680 AA homozygote was associated with a higher risk of IPA [odds ratio (OR) 18.86, 95% confidence interval (CI): 7.96–44.69; P<0.01], while no genotypic distribution differences were observed for the other 2 SNPs (rs2305619 and rs3816527). Six algorithms were established based on PTX3 gene polymorphisms. The algorithm consisting of PTX3 gene polymorphisms with adjusted BALF PTX3 and BALF GM values demonstrated the best diagnostic performance (sensitivity 90.03%; specificity 97.09%; area under the curve 0.94).ConclusionsIt was revealed that our new algorithm based on PTX3 gene polymorphisms combined with adjusted BALF GM and BALF PTX3 values performed well in diagnosing IPA.

Assessment of antimicrobial activity of bioflavonoid CITROX and chlorhexidine combination against P. gingivalis (in vitro)

The aim of the study - evaluation of the antiseptic properties of the combination of chlorhexidine and bioflavonoid CITROX against P. gingivalis. Clinical isolates of microbial cultures from the collection of the Department of Microbiology, Immunology, Virology of the Moscow State Medical University named after A.I. Evdokimov: P. gingivalis. Primary seeding of the studied material was carried out on nutrient media produced by Himedia Laboratories Pvt. Limited (India): Colombian agar with the addition of 5% defibrinated blood and a selective additive for the isolation of non-spore anaerobes. To conduct the experiment, a thermostatic rotary system - RTS-1 (Biosan, Latvia) was used, which performs a modern type of mixing due to the formation of a vortex-type diffusing effect. The interpretation of the results was carried out by changing the optical density index (the indicator in McFarland units) at a wavelength of λ = 850 nm. The combination of CITROX + chlorhexidine 0.05% more effectively suppresses the growth of periodotopathogenic bacteria than chlorhexidine 0.05%, prolonging the adaptive phase (lag phase) of the growth of P.gingivalis bacteria and can be considered as an alternative to chlorhexidine without additives. Prolongation of the lag phase increases the time until the first clinical symptoms appear, as a result, the body has more time to form an immune response. The combination of the complex of bioflavonoids CITROX and chlorhexidine bigluconate in concentrations of 0.05% and 0.2% is active against P. gingivalis and can be considered as an alternative to chlorhexidine without additives. The inclusion of CITROX in the rinse aid reduces the concentration of chlorhexidine in the rinse aid, which can lead to a decrease in the severity of undesirable effects and be considered as an alternative remedy in the treatment of periodontal diseases.