The relationship between lung CT features and serum cryptococcal antigen titers in localized pulmonary cryptococcosis patients.

BACKGROUND: To explore the associations of computed tomography (CT) image features with the serum cryptococcal antigen (CrAg) titers measured by the lateral flow assay (LFA) in localized pulmonary cryptococcosis patients. METHODS: A retrospective analysis of patients with pathologically confirmed pulmonary cryptococcosis admitted to the First Affiliated Hospital of Xiamen University from January 2016 to December 2022 was performed. Clinical data, CT results, serum CrAg-LFA test results, and follow-up data were collected and analyzed. RESULTS: A total of 107 patients with localized pulmonary cryptococcosis were included, of which 31 had a single lesion in chest CT and the other 76 had multiple lesions. The positivity rate was (94.74% vs 64.52%) and titers of serum CrAg-LFA (1.77 ± 0.87 vs 0.91 ± 0.98) in the multiple lesion group were higher than those in the single lesion group, respectively. Multivariate linear regression analysis showed that the serum CrAg titers were positively associated with the number of lesions (ß, 0.08; 95% CI, 0.05 to 0.12) and the lesion size (ß, 0.40; 95% CI, 0.31 to 0.50) after adjusting other covariates. The serum CrAg-LFA titers of 60 pulmonary cryptococcosis patients showed a decreasing trend with the reduction in pulmonary lesion size after effective therapy. CONCLUSION: In pulmonary cryptococcosis patients, the number and size of lung lesions are positively correlated with the titers of the serum CrAg-LFA test. The CrAg-LFA test could be a useful tool for the diagnosis, severity assessment, and therapeutic monitoring of localized pulmonary cryptococcosis patients.

LincR-PPP2R5C deficiency enhancing the fungicidal activity of neutrophils in pulmonary cryptococcosis is linked to the upregulation of IL-4.

Pulmonary cryptococcosis is a common complication in immunocompromised patients. In a mouse model of pulmonary cryptococcosis, Cryptococcus neoformans induces a type 2 immune response that is detrimental to host protection. Long non-coding RNAs (lncRNAs) have emerged as key players in the pathogenesis of infectious diseases. However, the roles and mechanisms of lncRNAs in fungal infection are largely elusive. In the present study, we aimed to explore the roles of LincR-PPP2R5C in pulmonary cryptococcosis. We observed an increase in the level of LincR-PPP2R5C in the lung tissues of C57BL/6J mice after tracheal infection with C. neoformans. Subsequently, we intratracheally infected LincR-PPP2R5C knockout (KO) mice and wild-type mice with C. neoformans. LincR-PPP2R5C deficiency mitigates C. neoformans infection, which can be demonstrated by extending survival time and decreasing fungal burden in the lung. In the lung tissues of infected LincR-PPP2R5C KO mice, there was a notable increase in the levels of type 2 cytokines [interleukin (IL)-4 and IL-5] and an increase in the number of neutrophils in both the lung tissue and bronchoalveolar lavage fluid. Mechanistically, the lack of LincR-PPP2R5C results in increased protein phosphatase 2A phosphorylation, thereby enhancing the fungicidal activity of neutrophils against Cryptococcus neoformans, with IL-4 playing a synergistic role in this process. Overall, LincR-PPP2R5C deficiency mitigated pulmonary cryptococcosis by increasing the fungicidal activity of neutrophils, which was associated with increased IL-4 levels. Our study presented specific evidence of the role of host-derived lncRNAs in the regulation of C. neoformans infection. IMPORTANCE: Pulmonary cryptococcosis is a human fungal disease caused by Cryptococcus neoformans, which is common not only in immunocompromised individuals but also in patients with normal immune function. Therefore, studying the control mechanisms of pulmonary cryptococcosis is highly important. Here, we demonstrated that the deletion of LincR-PPP2R5C leads to increased killing of C. neoformans by neutrophils, thereby reducing pulmonary cryptococcal infection. These findings will greatly enhance our understanding of the mechanisms by which lncRNAs regulate the pathogenesis of C. neoformans, facilitating the use of lncRNAs in pulmonary cryptococcosis therapy.

Lung adenocarcinoma concurrent with pulmonary cryptococcosis: a case report and literature review.

Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 F­FDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice.

Establishment of a predictive model of CT value in the diagnosis and differential diagnosis of pulmonary cryptococcosis.

Objective: To investigate the application value of computed tomography (CT) value (HU) in the diagnosis and differential diagnosis of pulmonary cryptococcosis (PC) and to construct a prediction model. Methods: Retrospective analysis of the clinical data of 73 patients who presented with nodular/mass-type occupations on lung CT and confirmed by histopathology in our hospital from January 2019 to May 2022 were divided into PC group (23 patients) and non-PC group (50 patients) according to the pathological findings, and the CT values of each patient's lung lesions were measured. The differences in age, gender, symptoms, lesion involvement in one/both lungs, lung lobe distribution, number of lesions, maximum lesion diameter (cm), lesion margin condition, and CT value results were compared between the two groups. Independent risk factors for PC were analyzed for indicators with statistically significant differences, clinical prediction models were constructed and column line plots were drawn, C (correction) indices were calculated, subject characteristics (ROC) curves were drawn, calibration curves and clinical decision curve analysis (DCA) were performed to further evaluate the predictive efficacy of the models. Results: Comparative analysis of patient data between the two groups showed statistically significant differences in central, peripheral and global CT values (P < 0.05), and multiple regression analysis indicated that central CT value, peripheral CT value and global CT value could be used as independent risk factors for the diagnosis and differential diagnosis of PC. The area under the ROC curve of the model predicting PC was 0.814 (95 % CI: 0.7011-0.9267), and the corrected C-index (Bootstrap = 1000) was 0.781; the actual curve overlapped well with the calibration curve; the DCA results indicated that the column line graph model has high clinical application value. Conclusions: CT value measurements of lesions can be used as an independent risk factor for PC, and clinical prediction models based on the above factors are predictive for the diagnosis and differential diagnosis of PC.

Pulmonary cryptococcosis in chronic kidney disease.

Pulmonary cryptococcosis is a fungal infection caused by Cryptococcus species, with Cryptococcus neoformans being the most common agent, affecting the lungs. While it commonly occurs in immunocompromised individuals, such as those with HIV/AIDS or undergoing immunosuppressive therapy, its presentation in patients with chronic kidney disease (CKD) is relatively rare. However, it should be considered in the differential diagnosis of respiratory infections in patients with CKD, particularly in the context of immunosuppression.

Clinical, radiological, and laboratory features of HIV-negative pulmonary cryptococcosis with regard to serum lateral flow assay.

Introduction: Cryptococcosis is the second most common invasive yeast infection in China. Pulmonary cryptococcosis (PC) is difficult to diagnose due to the lack of specific clinical features and the limitation of diagnostic techniques. Although lateral flow assay was very useful in diagnosing cryptococcal infection, quite a few patients with PC presented negative serum lateral flow assay (sLFA). Methods: We conducted a retrospective study of HIV-negative patients who were diagnosed with PC in our hospital over the past decade to explore the potential relationship between the clinical profiles and sLFA in PC. Results: In total, 112 patients with sLFA tested were enrolled in this study, of which 58.93% were male. The positivity rate of sLFA for PC was 91.07%. The extent of pulmonary lesions was positively correlated with sLFA grade (Spearman r = 0.268, p < 0.01). Solitary nodule (SN) and pneumonia were the most common imaging findings in PC with negative and positive sLFA respectively. Among 65 symptomatic PC patients, 14 presented with fever and had higher hypersensitive C-reactive protein (hsCRP) level and more extensive pulmonary involvement (Mann-Whitney U test, p < 0.05) than those without fever. Symptomatic PC patients were more likely to have positive results of sLFA (Mann-Whitney U test, p = 0.05) compared against asymptomatic ones. Discussion: In conclusion, negative sLFA cannot exclude PC in patients with a solitary nodule in lung. Positive sLFA is more reliable in diagnosing PC in symptomatic patients with diffused lesions in lung who generally experience a more severe systemic inflammatory reaction.

Pulmonary Cryptococcosis: A Diagnostic and Management Challenge Case Report.

Cryptococcosis is a fungal infection that may arise in immunocompromised or immunocompetent individuals. This case report seeks to demonstrate the difficulty in diagnosing and treating cryptococcosis based on clinical presentation and radiographic features as together, they mimic other pathological conditions. A 56-year-old female with cirrhosis presented with persistent abdominal pain, dyspnea, vomiting, and diarrhea and was diagnosed with pulmonary cryptococcosis after an initial diagnosis of bacterial pneumonia. With no improvement following antibiotic therapy for suspected bacterial pneumonia, additional imaging was performed with a confirmatory lung biopsy for pulmonary cryptococcosis. The patient initiated antifungal therapy with the anticipation of completing approximately 12 months with follow-up imaging to evaluate improvement. After the patient experienced adverse effects of antifungal therapy and did not achieve significant improvement or recovery in her condition, it was apparent that cryptococcal pneumonia presents both diagnostic and management challenges that must be further explored.

Construction and validation of a nomogram model to predict the poor prognosis in patients with pulmonary cryptococcosis.

Background: Patients with poor prognosis of pulmonary cryptococcosis (PC) are prone to other complications such as meningeal infection, recurrence or even death. Therefore, this study aims to analyze the influencing factors in the poor prognosis of patients with PC, so as to build a predictive nomograph model of poor prognosis of PC, and verify the predictive performance of the model. Methods: This retrospective study included 410 patients (78.1%) with improved prognosis of PC and 115 patients (21.9%) with poor prognosis of PC. The 525 patients with PC were randomly divided into the training set and validation set according to the ratio of 7:3. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to screen the demographic information, including clinical characteristics, laboratory test indicators, comorbidity and treatment methods of patients, and other independent factors that affect the prognosis of PC. These factors were included in the multivariable logistic regression model to build a predictive nomograph. The receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to verify the accuracy and application value of the model. Results: It was finally confirmed that psychological symptoms, cytotoxic drugs, white blood cell count, hematocrit, platelet count, CRP, PCT, albumin, and CD4/CD8 were independent predictors of poor prognosis of PC patients. The area under the curve (AUC) of the predictive model for poor prognosis in the training set and validation set were 0.851 (95% CI: 0.818-0.881) and 0.949, respectively. At the same time, calibration curve and DCA results confirmed the excellent performance of the nomogram in predicting poor prognosis of PC. Conclusion: The nomograph model for predicting the poor prognosis of PC constructed in this study has good prediction ability, which is helpful for improving the prognosis of PC and further optimizing the clinical management strategy.

Value of rapid on-site evaluation combined with interventional pulmonology techniques in the diagnosis of pulmonary cryptococcosis.

OBJECTIVES: The aim of this study is to evaluate the diagnostic value of rapid on-site evaluation (ROSE) combined with computed tomography-guided percutaneous needle biopsy (CT-PNB) or radial endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) for pulmonary cryptococcosis (PC). METHODS: Clinical data of 33 patients diagnosed with PC at the Third Affiliated Hospital of Soochow University between February 2018 and June 2023 were retrospectively analysed. Patients were divided into the CT-PNB and EBUS-TBLB groups based on the intervention method, and the diagnostic positivity rate and incidence of complications were compared between the two groups. RESULTS: Compared with the final diagnosis, the positive diagnostic rates of ROSE, histopathology and serum CrAg of all patients were 81.8% (27/33), 72.7% (24/33) and 63.6% (21/33), respectively. The average turnaround times of the three methods were 0.1 (0.1-0.2) h, 96.0 (48.0-120.0) h and 7.8 (4.5-13.6) h, respectively (P < 0.001). The coincidence rate between histopathology and ROSE was 84.8% with a kappa value of 0.574. The positive diagnostic rate for PC was significantly higher in the CT-PNB group than in the EBUS-TBLB group (92.9% vs. 57.9%), and the difference was statistically significant (P < 0.05). Combined with the ROSE results, the positive diagnostic rate in the EBUS-TBLB group increased to 84.2% (16/19). CONCLUSION: ROSE has commendable accuracy and timeliness, and CT-PNB offers further advantages in this regard. ROSE enhances the diagnostic efficiency of EBUS-TBLB for PC and is safe and effective.

Cryptococcosis with pulmonary cavitation in an immunocompetent child: a case report and literature review.

BACKGROUND: Pulmonary cryptococcosis (PC) rarely occurs in immunocompetent children. CASE PRESENTATION: A 13-year-old boy was admitted to the First Affiliated Hospital of Ningbo University in February 2023 with complaints of cough and chest pain. Physical examination showed slightly moist rales in the right lung. Chest computed tomography (CT) suggested a lung lesion and cavitation. Blood routine test, lymphocyte subsets, immunoglobulin, and complement tests indicated that the immune system was normal. However, the serum cryptococcal antigen test was positive. Next-generation sequencing revealed Cryptococcus infection. The child was diagnosed with PC and was discharged after treating with fluconazole 400 mg. Four months later, chest CT showed that the lung lesion diminished, and reexamination of serum cryptococcal antigen test turned positive. CONCLUSION: PC should be considered in an immunocompetent child with pulmonary cavities with nonspecific symptoms.

Supervised training models with or without manual lesion delineation outperform clinicians in distinguishing pulmonary cryptococcosis from lung adenocarcinoma on chest CT.

BACKGROUND: The role of artificial intelligence (AI) in the discrimination between pulmonary cryptococcosis (PC) and lung adenocarcinoma (LA) warrants further research. OBJECTIVES: To compare the performances of AI models with clinicians in distinguishing PC from LA on chest CT. METHODS: Patients diagnosed with confirmed PC or LA were retrospectively recruited from three tertiary hospitals in Guangzhou. A deep learning framework was employed to develop two models: an undelineated supervised training (UST) model utilising original CT images, and a delineated supervised training (DST) model utilising CT images with manual lesion annotations provided by physicians. A subset of 20 cases was randomly selected from the entire dataset and reviewed by clinicians through a network questionnaire. The sensitivity, specificity and accuracy of the models and the clinicians were calculated. RESULTS: A total of 395 PC cases and 249 LA cases were included in the final analysis. The internal validation results for the UST model showed a sensitivity of 85.3%, specificity of 81.0%, accuracy of 83.6% and an area under the curve (AUC) of 0.93. Similarly, the DST model exhibited a sensitivity of 88.2%, specificity of 88.1%, accuracy of 88.2% and an AUC of 0.94. The external validation of the two models yielded AUC values of 0.74 and 0.77, respectively. The average sensitivity, specificity and accuracy of 102 clinicians were determined to be 63.1%, 53.7% and 59.3%, respectively. CONCLUSIONS: Both models outperformed the clinicians in distinguishing between PC and LA on chest CT, with the UST model exhibiting comparable performance to the DST model.

Pulmonary cryptococcosis complicated with pulmonary aspergillosis: a series of studies and a literature review.

BACKGROUND/OBJECTIVE: With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common. However, there is a lack of clear understanding regarding coinfection by these two types of fungi in immunocompetent individuals. METHODS: A retrospective study from 2014 to 2022 and a systematic literature review of original articles published in English were performed. Patients with pulmonary cryptococcosis complicated with pulmonary aspergillosis including 5 in the retrospective study and 6 in the systematic literature review. RESULT: The diagnosis of concurrent pulmonary cryptococcosis and pulmonary aspergillosis in patients was confirmed through repeated biopsies or surgical resection. Pulmonary cryptococcosis is often diagnosed initially (6/11, 55%), while the diagnosis of pulmonary aspergillosis is established when the lesions become fixed or enlarged during treatment. Transbronchial lung biopsy (3/11, 27%), thoracoscopic lung biopsy (2/11, 18%), and percutaneous aspiration biopsy of the lung (1/11, 9%) were the main methods to confirm concurrent infection. Most patients were treated with voriconazole, resulting in a cure for the coinfection (6/11, 55%). CONCLUSION: Pulmonary cryptococcosis complicated with pulmonary Aspergillus is an easily neglected mixed fungal infection. During the treatment of lesion enlargement in clinical cryptococcus, we need to watch out for Aspergillus infection.

Pulmonary cryptococcosis coexisting with lung adenocarcinoma: A case report and review of the literature.

Pulmonary cryptococcosis (PC) is an invasive pulmonary fungal disease caused by Cryptococcus neoformans or Cryptococcus gattii. It often presents as a single nodule or mass on radiology, which is easily misdiagnosed as lung cancer or metastases. However, cases of PC coexisting with lung cancer are rare and when this scenario is encountered in clinical practice, it is easy to be misdiagnosed as metastatic lung cancer. The present study reported the case of a 65-year-old immunocompetent patient with PC coexisting with lung adenocarcinoma. Percutaneous lung biopsy was performed on the nodule in the anterior segment of the left upper lobe and the nodule in the posterior basal segment of the left lower lobe, which were diagnosed as primary adenocarcinoma and cryptococcus, respectively. Lung cancer was treated by surgery and PC was treated successfully by antifungal treatment. During the 5-year follow-up, contrast-enhanced CT showed no recurrence of either disease. This case reminds us of the possibility of dualism in the diagnosis of multiple pulmonary nodules based on CT examination, such as the coexistence of lung carcinoma and PC. In addition, early diagnosis and treatment contribute to good prognosis.

A Case of Pulmonary Cryptococcosis Caused by Capsule-Deficient Cryptococcus neoformans.

Cryptococcosis, a fungal infection primarily caused by Cryptococcus neoformans (CN), is a significant concern for immunocompromised individuals. This paper presents a case of a 51-year-old immunocompromised male who initially presented with symptoms suggestive of community-acquired pneumonia but was later diagnosed with pulmonary cryptococcosis caused by capsule-deficient CN. The patient's exposure to construction dust, coupled with his immunocompromised state due to immunosuppressive treatment for psoriatic arthritis, likely contributed to his susceptibility. The unique presentation of the disease, due to the absence of the characteristic thick capsule, presented a diagnostic challenge. A brief review is provided looking at the mechanism, pathogenesis, and implications of capsule deficiency in CN. The case provides an example of one of the many presentations of cryptococcosis, especially in immunocompromised individuals, and highlights the diagnostic complexities of capsule-deficient CN strains.

Identification of risk factors for disseminated cryptococcosis in non-hiv patients: a retrospective analysis.

OBJECTIVE: This study aimed to investigate the potential risk factors associated with disseminated cryptococcosis in HIV-negative individuals. METHODS: A total of 106 HIV-negative patients with cryptococcal disease were enrolled. The observation group consisted of patients with disseminated cryptococcosis (DC), whereas the control groups included patients with pulmonary cryptococcosis (PC) and cryptococcal meningitis (CM). Univariate and multivariate logistic regression algorithms were used to explore the significant clinical and laboratory characteristics that affect the progression of cryptococcal infections. Finally, receiver operating characteristics (ROC) curves are applied to assess the diagnostic value of identified risk factors.LE: Kindly check the edit made in the title.I agree RESULTS: Of the 106 patients, 57 were diagnosed with pulmonary cryptococcosis, 22 with cryptococcal meningitis, and 27 with disseminated cryptococcosis. The logistic regression equation included five variables: diabetes, decompensated liver cirrhosis, long-term use of immunosuppressive agents, decreased serum albumin level, and elevated plasma cytokine IL-10 level. The ROC curves showed that albumin (AUC > 0.7), IL-10 (AUC > 0.7) and decompensated liver cirrhosis (AUC > 0.6) have relatively high diagnostic capacity in predicting the progression of Cryptococcus. CONCLUSION: This study identified elevated IL-10 levels as an independent risk factor for developing disseminated cryptococcosis in the control groups. Furthermore, decompensated liver cirrhosis and decreased serum albumin independently affected the progression of cryptococcosis in the CM and PC groups, respectively.

Serum sphingolipids aid in diagnosing adult HIV-negative patients with pulmonary cryptococcosis: a clinical cohort study.

Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.

Performance of Cryptococcal Antigen Lateral Flow Assay in Bronchoalveolar Lavage Fluid in HIV-Negative Patients.

OBJECTIVE: We presented the performance of cryptococcal antigen lateral flow assay test using bronchoalveolar lavage fluid (BALF) samples in the HIV-negative Chinese population. METHODS: From January 2019 to June 2022, cryptococcal antigen was detected in both serum and BALF samples from 113 patients with suspected pulmonary cryptococcosis. RESULTS: 49 patients were finally diagnosed with pulmonary cryptococcosis. The sensitivity of cryptococcal antigen lateral flow assay test in serum and BALF specimens from confirmed cases was 90.0% and 96.0%, respectively, and the specificity was 87.3% and 95.5%, respectively. When the diameter of the lung lesion was less than 15 mm, the antigen positivity rate of BALF was higher than that of serum. Moreover, the result of the cryptococcal antigen test was associated with the lymphocytes count of BALF. CONCLUSION: Our data demonstrate that cryptococcal antigen Lateral Flow Assay for BALF specimens might contribute to the early diagnosis of pulmonary cryptococcosis.

Ethanolic Extract Propolis-Loaded Niosomes Diminish Phospholipase B1, Biofilm Formation, and Intracellular Replication of Cryptococcus neoformans in Macrophages.

Secretory phospholipase B1 (PLB1) and biofilms act as microbial virulence factors and play an important role in pulmonary cryptococcosis. This study aims to formulate the ethanolic extract of propolis-loaded niosomes (Nio-EEP) and evaluate the biological activities occurring during PLB1 production and biofilm formation of Cryptococcus neoformans. Some physicochemical characterizations of niosomes include a mean diameter of 270 nm in a spherical shape, a zeta-potential of -10.54 ± 1.37 mV, and 88.13 ± 0.01% entrapment efficiency. Nio-EEP can release EEP in a sustained manner and retains consistent physicochemical properties for a month. Nio-EEP has the capability to permeate the cellular membranes of C. neoformans, causing a significant decrease in the mRNA expression level of PLB1. Interestingly, biofilm formation, biofilm thickness, and the expression level of biofilm-related genes (UGD1 and UXS1) were also significantly reduced. Pre-treating with Nio-EEP prior to yeast infection reduced the intracellular replication of C. neoformans in alveolar macrophages by 47%. In conclusion, Nio-EEP mediates as an anti-virulence agent to inhibit PLB1 and biofilm production for preventing fungal colonization on lung epithelial cells and also decreases the intracellular replication of phagocytosed cryptococci. This nano-based EEP delivery might be a potential therapeutic strategy in the prophylaxis and treatment of pulmonary cryptococcosis in the future.

A CT-based radiomics integrated model for discriminating pulmonary cryptococcosis granuloma from lung adenocarcinoma-a diagnostic test.

Background: Chest computed tomography (CT) is a critical tool in the diagnosis of pulmonary cryptococcosis as approximately 30% of normal immunity individuals may not exhibit any significant symptoms or laboratory findings. Pulmonary cryptococcosis granuloma and lung adenocarcinoma can appear similar on noncontrast chest CT. This study evaluates the use of an integrated model that was developed based on radiomic features combined with demographic and radiological features to differentiate pulmonary cryptococcosis nodules from lung adenocarcinomas. Methods: Preoperative chest CT images for 215 patients with solid pulmonary nodules with histopathologically confirmed lung adenocarcinoma and cryptococcosis infection were collected from two clinical centers (108 cases in the training set and 107 cases in the test set divided by the different hospitals). Radiomics models were constructed based on nodular lesion volume (LV), 5-mm extended lesion volume (ELV), and perilesion volume (PLV). A demoradiological model was constructed using logistic regression based on demographic information (age, sex) and 12 radiological features (location, number, shape and specific imaging signs). Both models were used to build an integrated model, the performance of which was assessed using the test set. A junior and a senior radiologist evaluated the nodules. Receiver operating characteristic (ROC) curve analysis was conducted, and areas under the curve (AUCs), sensitivity (SEN), and specificity (SPE) of the models were calculated and compared. Results: Among the radiomics models, AUCs of the LV, ELV, and PLV were 0.558, 0.757, and 0.470, respectively. Age, lesion number, and lobular sign were identified as independent discriminative features providing an AUC of 0.77 in the demoradiological model (SEN 0.815, SPE 0.642). The integrated model achieved the highest AUC of 0.801 (SEN 0.759, SPE 0.755), which was significantly higher than that obtained by a junior radiologist (AUC =0.689, P=0.024) but showed no significant difference from that of the senior radiologist (AUC =0.784, P=0.388). Conclusions: An integrated model with radiomics and demoradiological features improves discrimination of cryptococcosis granulomas from solid adenocarcinomas on noncontrast CT. This model may be an effective strategy for machine complementation to discrimination by radiologists, and whole-lung automated recognition methods might dominate in the future.