MI-DenseCFNet: deep learning-based multimodal diagnosis models for Aureus and Aspergillus pneumonia.

OBJECTIVE: To build and merge a diagnostic model called multi-input DenseNet fused with clinical features (MI-DenseCFNet) for discriminating between Staphylococcus aureus pneumonia (SAP) and Aspergillus pneumonia (ASP) and to evaluate the significant correlation of each clinical feature in determining these two types of pneumonia using a random forest dichotomous diagnosis model. This will enhance diagnostic accuracy and efficiency in distinguishing between SAP and ASP. METHODS: In this study, 60 patients with clinically confirmed SAP and ASP, who were admitted to four large tertiary hospitals in Kunming, China, were included. Thoracic high-resolution CT lung windows of all patients were extracted from the picture archiving and communication system, and the corresponding clinical data of each patient were collected. RESULTS: The MI-DenseCFNet diagnosis model demonstrates an internal validation set with an area under the curve (AUC) of 0.92. Its external validation set demonstrates an AUC of 0.83. The model requires only 10.24s to generate a categorical diagnosis and produce results from 20 cases of data. Compared with high-, mid-, and low-ranking radiologists, the model achieves accuracies of 78% vs. 75% vs. 60% vs. 40%. Eleven significant clinical features were screened by the random forest dichotomous diagnosis model. CONCLUSION: The MI-DenseCFNet multimodal diagnosis model can effectively diagnose SAP and ASP, and its diagnostic performance significantly exceeds that of junior radiologists. The 11 important clinical features were screened in the constructed random forest dichotomous diagnostic model, providing a reference for clinicians. CLINICAL RELEVANCE STATEMENT: MI-DenseCFNet could provide diagnostic assistance for primary hospitals that do not have advanced radiologists, enabling patients with suspected infections like Staphylococcus aureus pneumonia or Aspergillus pneumonia to receive a quicker diagnosis and cut down on the abuse of antibiotics. KEY POINTS: • MI-DenseCFNet combines deep learning neural networks with crucial clinical features to discern between Staphylococcus aureus pneumonia and Aspergillus pneumonia. • The comprehensive group had an area under the curve of 0.92, surpassing the proficiency of junior radiologists. • This model can enhance a primary radiologist's diagnostic capacity.

Radiological Diagnosis of Pulmonary Aspergillosis.

Imaging plays an important role in the various forms of Aspergillus-related pulmonary disease. Depending on the immune status of the patient, three forms are described with distinct imaging characteristics: invasive aspergillosis affecting severely immunocompromised patients, chronic pulmonary aspergillosis affecting less severely immunocompromised patients but suffering from a pre-existing structural lung disease, and allergic bronchopulmonary aspergillosis related to respiratory exposure to Aspergillus species in patients with asthma and cystic fibrosis. Computed tomography (CT) has been demonstrated more sensitive and specific than chest radiographs and its use has largely contributed to the diagnosis, follow-up, and evaluation of treatment in each condition. In the last few decades, CT has also been described in the specific context of cystic fibrosis. In this particular clinical setting, magnetic resonance imaging and the recent developments in artificial intelligence have shown promising results.

Chronic cavitary pulmonary aspergillosis: Serial clinical and CT findings correlated with antifungal treatment and patient response.

BACKGROUND: Chronic cavitary pulmonary aspergillosis (CCPA) is the most common form of chronic pulmonary aspergillosis. OBJECTIVE: We hypothesise that by observing serial clinical and CT findings of CCPA patients with antifungal therapy, factors helping predict responses to antifungal therapy could be withdrawn. METHODS: A total of 31 patients with CCPA who received antifungal therapy for greater than six months and who had serial CT studies were included. Clinical finding analyses were performed at initial and last follow-up CT acquisition dates. Clinical characteristics and CT features were compared between clinically improving or stable and deteriorating groups. RESULTS: With antifungal therapy, neutrophil-to-lymphocyte ratio (2.66 vs. 5.12, p = .038) and serum albumin (4.40 vs. 3.85 g/dl, p = .013) and CRP (1.10 vs. 42.80 mg/L, p = .007) were different between two groups. With antifungal therapy, meaningful CT change, regardless of clinical response grouping, was decrease in cavity wall thickness (from 13.70 mm to 8.28 mm, p < .001). But baseline (p = .668) and follow-up (p = .278) cavity wall thickness was not different between two groups. In univariate analysis, initial maximum diameter of cavity (p = .028; HR [0.983], 95% CI [0.967-0.998]) and concurrent NTM infection (p = .030; HR [0.20], 95% CI [0.05-0.86]) were related factors for poor clinical response. CONCLUSIONS: With antifungal therapy, cavities demonstrate wall thinning. Of all clinical and radiological findings and their changes, initial large cavity size and concurrent presence of NTM infection are related factors to poor response to antifungal therapy.

Covid-19 associated pulmonary aspergillosis with extensive cavitary pneumonia: A case report.

Covid-19 associated pulmonary aspergillosis (CAPA) is a new entity and is associated with high morbidity and mortality. Covid-19 is a pro-inflammatory and immunosuppressive disease, provoking fungal infections, especially by Aspergillus species. We describe the case of a critically ill Covid-19 female patient, who was diagnosed with CAPA infection and acute respiratory distress syndrome (ARDS). She was given intravenous Remdesivir. Her chest X-ray a few days after admission showed multiple cavities. Her condition initially improved but deteriorated again, with worsening hypoxia and pneumothorax and multiple cavitary lesions on HRCT of the chest. Despite optimal treatment, she could not recover. Interestingly, she had no predisposing risk factor for pulmonary aspergillosis, such as chronic lung disease, diabetes or use of immunosuppressants such as Tocilizumab. CAPA is an emerging entity with worsening hypoxia, and failure to improve can be an early sign. Early identification and treatment can improve survival and outcomes in Covid-19 patients.

A prospective longitudinal study of chronic pulmonary aspergillosis in pulmonary tuberculosis in Indonesia (APICAL).

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary TB. CPA may also be misdiagnosed as bacteriologically negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia, a country with a high incidence of TB. METHODS: In this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0-8 weeks) and at the end (5-6 months) of TB therapy. CPA diagnosis was based on symptoms (≥3 months), characteristic radiological features and positive Aspergillus serology, and categorised as proven, probable and possible. RESULTS: Of the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence rates of proven and probable CPA at baseline were 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (two with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA. CONCLUSION: CPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.

Pulmonary aspergilloma on transthoracic ultrasound.

PURPOSE: Pulmonary aspergilloma affects immunocompromised patients but is also a recurrent condition in patients previously treated for pulmonary tuberculosis. METHODS AND RESULTS: We report the case of a 45-year-old patient with a history of cured pulmonary tuberculosis 15 years earlier in whom we visualized pulmonary aspergilloma by transthoracic lung sonography. Sonography of pulmonary aspergilloma demonstrated an oval cavity with hypoechoic contents and an irregular border, measuring a diameter of 4.7 cm; inside the lesion, a roundish structure with an anechoic rim was discernable. CONCLUSIONS: The sonographic findings corresponded to chest X-ray and computed tomography imaging in this patient and to previously reported sonographic characteristics of mycotic abscesses in other organs. Lung ultrasound may be a tool to identify pulmonary aspergilloma, especially as a point-of-care imaging tool and where other imaging modalities are inaccessible.

Pulmonary Aspergillosis in Patients with Suspected Ventilator-associated Pneumonia in UK ICUs.

Rationale:Aspergillus infection in patients with suspected ventilator-associated pneumonia remains uncharacterized because of the absence of a disease definition and limited access to sensitive diagnostic tests.Objectives: To estimate the prevalence and outcomes of Aspergillus infection in adults with suspected ventilator-associated pneumonia.Methods: Two prospective UK studies recruited 360 critically ill adults with new or worsening alveolar shadowing on chest X-ray and clinical/hematological parameters supporting suspected ventilator-associated pneumonia. Stored serum and BAL fluid were available from 194 nonneutropenic patients and underwent mycological testing. Patients were categorized as having probable Aspergillus infection using a definition comprising clinical, radiological, and mycological criteria. Mycological criteria included positive histology or microscopy, positive BAL fluid culture, galactomannan optical index of 1 or more in BAL fluid or 0.5 or more in serum.Measurements and Main Results: Of 194 patients evaluated, 24 met the definition of probable Aspergillus infection, giving an estimated prevalence of 12.4% (95% confidence interval, 8.1-17.8). All 24 patients had positive galactomannan in serum (n = 4), BAL fluid (n = 16), or both (n = 4); three patients cultured Aspergillus sp. in BAL fluid. Patients with probable Aspergillus infection had a significantly longer median duration of critical care stay (25.5 vs. 15.5 d, P = 0.02). ICU mortality was numerically higher in this group, although this was not statistically significant (33.3% vs. 22.8%; P = 0.23).Conclusions: The estimated prevalence for probable Aspergillus infection in this geographically dispersed multicenter UK cohort indicates that this condition should be considered when investigating patients with suspected ventilator-associated pneumonia, including patient groups not previously recognized to be at high risk of aspergillosis.

Proven Aspergillus flavus pulmonary aspergillosis in a COVID-19 patient: A case report and review of the literature.

Severe COVID-19 patients complicated with aspergillosis are increasingly reported. We present a histopathological proven case of fatal COVID-19-associated pulmonary aspergillosis (CAPA), due to Aspergillus flavus. This report and existing published literature indicate diagnostic challenges and poor outcomes of CAPA in ICU patients.

Hydatid disease with Aspergilloma: A unique case report.

The coexisting presence of hydatid disease with aspergillus colonization is a rare finding. The 20-year-old presented with symptoms of hemoptysis with past history of tuberculosis. On further evaluation, the patient was diagnosed as a case of aspergilloma and managed conservatively. After one year of presenting with similar complaints, the patient was turned out to be hydatid disease with aspergillus colonization on the basis of clinic-radiological and bronchoscopic evaluation. Till now only a few case reports have been reported. We report a unique case report of a similar presentation.

A Rare Complication: Development of an Aspergilloma after Endobronchial Coil Placement in a COPD Patient.

Endobronchial coils are a relatively novel endoscopic lung volume reduction modality that aims to increase functional capacity in chronic obstructive pulmonary disease (COPD) patients. Two major trials have studied the safety and efficacy of this therapy, but long-term safety has not been studied. Adverse events reported are mainly periprocedural pneumothoraces and early bacterial infectious complications. We report the case of a patient with severe emphysema (Global Initiative for Chronic Obstructive Lung Disease stage IV COPD) who developed endobronchial coil-associated aspergillomas 3 years after coil placement.

COVID-19 associated pulmonary aspergillosis.

OBJECTIVES: Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus disease 19 (COVID-19) associated invasive aspergillosis at a single centre in Cologne, Germany. METHODS: A retrospective chart review of all patients with COVID-19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany. RESULTS: COVID-19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS. CONCLUSION: Clinicians caring for patients with ARDS due to COVID-19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co-infection.

ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo.

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and tested a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging. Administration of a [(64)Cu]DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus-infected mice allowed specific localization of lung infection when combined with PET. Optical imaging with a fluorochrome-labeled version of the mAb showed colocalization with invasive hyphae. The mAb-based newly developed PET tracer [(64)Cu]DOTA-JF5 distinguished IPA from bacterial lung infections and, in contrast to [(18)F]FDG-PET, discriminated IPA from a general increase in metabolic activity associated with lung inflammation. To our knowledge, this is the first time that antibody-guided in vivo imaging has been used for noninvasive diagnosis of a fungal lung disease (IPA) of humans, an approach with enormous potential for diagnosis of infectious diseases and with potential for clinical translation.

Bronchial arterial embolization using a gelatin sponge for hemoptysis from pulmonary aspergilloma: comparison with other pulmonary diseases.

PURPOSE: To evaluate the clinical outcomes of bronchial artery embolization (BAE) using a gelatin sponge for hemoptysis from pulmonary aspergilloma and compare them with treatment outcomes for hemoptysis from other diseases. METHODS: Fifty-two patients underwent BAE using a gelatin sponge. The etiology of hemoptysis was pulmonary aspergilloma in 8 (PA group) and other diseases in 44 (control group). The technical success rate, clinical success rate, hemoptysis-free rate, and complication rate were compared between the PA group and control group. Technical success was defined as the complete cessation of the targeted feeding artery as confirmed by digital subtraction angiography, and clinical success as the cessation of hemoptysis within 24 h of BAE. Recurrent hemoptysis was defined as a single or multiple episodes of hemoptysis causing > 30 ml of bleeding per day. RESULTS: Technical and clinical success rates were 100% in both groups. Hemoptysis-free rates were 85% at 6 months and 72% at 12-60 months in the control group, and 38% at 6-12 months and 25% thereafter in the PA group (P = 0.0009). No complications were observed following BAE in any case in the two groups. CONCLUSION: BAE using a gelatin sponge may not be effective for hemoptysis from pulmonary aspergilloma.

The scab-like sign: A CT finding indicative of haemoptysis in patients with chronic pulmonary aspergillosis?

OBJECTIVES: The aim of this study was to assess the CT findings that characterise haemoptysis in patients with chronic pulmonary aspergillosis (CPA). METHODS: We retrospectively identified 120 consecutive patients with CPA (84 men and 36 women, 17-89 years of age, mean age 68.4 years) who had undergone a total of 829 CT examinations between January 2007 and February 2017. In the 11 patients who underwent surgical resection, CT images were compared with the pathological results. RESULTS: The scab-like sign was seen on 142 of the 829 CT scans, specifically, in 87 of the 90 CT scans for haemoptysis and in 55 of the 739 CT scans obtained during therapy evaluation. In 48 of those 55 patients, haemoptysis occurred within 55 days (mean 12.0 days) after the CT scan. In the 687 CT scans with no scab-like sign, there were only three instances of subsequent haemoptysis in the respective patients over the following 6 months. Patients with and without scab-like sign differed significantly in the frequency of haemoptysis occurring after a CT scan (p<0.0001). Pathologically, the scab-like sign corresponded to a fibrinopurulent mass or blood crust. CONCLUSIONS: The scab-like sign should be considered as a CT finding indicative of haemoptysis. KEY POINTS: • Haemoptysis is commonly found in patients with CPA. • A CT finding indicative of haemoptysis in CPA patients is described. • Scab-like sign may identify CPA patients at higher risk of haemoptysis.

The development of pulmonary aspergillosis and its histologic, clinical, and radiologic manifestations.

Pulmonary syndromes following exposure to Aspergillus sp. have a variety of clinical and radiological manifestations. The radiological manifestations mirror the pathophysiological response to Aspergillus sp., which is linked closely to the patient's immune status. The plethora of terms in the literature can be confusing and their application with relevance to radiological imaging may subsequently result in inadequate or non-specific classification. In this review, we aim to provide a simplified and up-to-date approach to the recognition of the imaging manifestations of pulmonary aspergillosis, using correlation with histopathological and clinical descriptors. This will enable the radiologist to utilise the imaging findings to instigate clinically useful and appropriate management for those patients at risk of significant morbidity and mortality.

Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives.

Chronic pulmonary aspergillosis (CPA) complicates conditions including tuberculosis, chronic obstructive pulmonary disease and sarcoidosis, and is associated with high morbidity and mortality. Surgical cure should be considered where feasible; however, many patients are unsuitable for surgery due to extensive disease or poor respiratory function. Azoles are the only oral drug with anti-Aspergillus activity and itraconazole and voriconazole are considered as first-line drugs. A randomized controlled trial demonstrated improvement or stability in three-quarters of patients given 6 months of itraconazole, but a quarter relapsed on stopping therapy. Long-term treatment may therefore be required in some cases. Itraconazole, voriconazole and posaconazole require therapeutic drug monitoring. No published data are yet available for isavuconazole. Adverse drug effects of azoles are common, including peripheral neuropathy, heart failure, elevated liver enzymes, QTc prolongation and sun sensitivity. Many serious drug-drug interactions occur, including major interactions with rifamycins, simvastatin, warfarin, clopidogrel, immunosuppressant drugs like sirolimus. Furthermore, drug resistance occurs, including cross-resistance to all azoles, but the true prevalence is not yet determined. Intravenous therapy is possible with echinocandins or amphotericin B, but long-term use is challenging. Hemoptysis complicates CPA and can be fatal. Tranexamic acid should be given acutely to reduce bleeding. Bronchial artery embolization can stop acute bleeds. In some circumstances, emergency surgery may be necessary to resect the source of the bleed. Current CPA treatments can be beneficial but have many drawbacks. New oral anti-Aspergillus agents are needed, along with optimization of currently available treatments.

Infectious and Non-Infectious Diseases Causing the Air Crescent Sign: A State-of-the-Art Review.

Aspergilloma, also known as mycetoma or fungus ball, is characterized by a round or oval mass with soft-tissue attenuation within a preexisting lung cavity. The typical computed tomography (CT) aspect of an aspergilloma is a mass separated from the wall of the cavity by an airspace of variable size and shape, resulting in the air crescent sign, also known as the meniscus sign. This CT feature is non-specific and can be simulated by several other entities that result in intracavitary masses. This review describes the main clinical and imaging aspects of the infectious and non-infectious diseases that may present with fungus-ball appearance, including pulmonary hydatid cyst, Rasmussen aneurysm, pulmonary gangrene, intracavitary clot, textiloma, lung cancer, metastasis, and teratoma, focusing on the differential diagnosis.

The Diagnostic Yield, Safety, and Impact of Flexible Bronchoscopy in Non-HIV Immunocompromised Critically Ill Patients in the Intensive Care Unit.

BACKGROUND: Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) have major roles in the evaluation of parenchymal lung diseases in immunocompromised patients. Given the limited evidence, lack of standardized practice, and variable perception of procedural safety, uncertainty still exists on what constitutes the best approach in critically ill patients with immunocompromised state who present with pulmonary infiltrates in the era of prophylactic antimicrobials and the presence of new diagnostic tests. OBJECTIVE: To evaluate the diagnostic yield, safety and impact of FB and BAL on management decisions in immunocompromised critically ill patients admitted to the intensive care unit (ICU). METHODS: A prospective, observational study of 106 non-HIV immunocompromised patients admitted to the intensive care unit with pulmonary infiltrates who underwent FB with BAL. RESULTS: FB and BAL established the diagnosis in 38 (33%) of cases, and had a positive impact on management in 44 (38.3%) of cases. Escalation of ventilator support was not required in 94 (81.7%) of cases, while 18 (15.7%) required invasive and 3 (2.6%) required non-invasive positive pressure ventilation after the procedure. Three patients (2.6%) died within 24 h of bronchoscopy, and 46 patients (40%) died in ICU. Significant hypoxemia developed in 5% of cases. CONCLUSION: FB can be safely performed in immunocompromised critically ill patients in the ICU. The yield can be improved when FB is done prior to initiation of empiric antimicrobials, within 24 h of admission to the ICU, and in patients with focal disease.