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Cheng Q, Tang Y, Liu J, Liu F, Li X. The Differential Diagnostic Value of Chest Computed Tomography for the Identification of Pathogens Causing Pulmonary Infections in Patients with Hematological Malignancies. Infect Drug Resist 2024; 17:4557-4566. [PMID: 39464837 PMCID: PMC11505564 DOI: 10.2147/idr.s474229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 10/12/2024] [Indexed: 10/29/2024] Open
Abstract
Objective The role of chest computed tomography (CT) in distinguishing the causative pathogens of pulmonary infections in patients with hematological malignancies (HM) is unclear. The aim of our study was to compare and assess the clinical characteristics, radiologic features and potential differential diagnostic value of CT in HM patients and other different immune statuses patients with pulmonary infections. Methods Patients were divided into immunocompetent (105 cases) and immunocompromised groups (99 cases) according to immune status. Immunocompromised patients included the HM group (63 cases) and the non-HM group (42 cases). The basic clinical data and CT findings were collected and statistically analyzed. Results Regarding the pathogen distribution, viral, Pneumocystis jirovecii and mixed infections were more common in the immunocompromised group than the immunocompetent (p < 0.01), but viral infections were more common in the HM group than in the non-HM group (p=0.013). Immunocompromised patients had more diverse CT findings and more serious lesions (mostly graded 2-4) than immunocompetent patients. The most common CT findings in HM patients were consolidation and ground-glass opacities (GGO), which were also found in the non-HM group. The overall diagnostic accuracy of CT was lower in immunocompromised patients than in immunocompetent patients (25.7% vs 50.5%, p< 0.01). CT had better diagnostic efficacy for fungi and Pneumocystis jirovecii in HM patients. Conclusion CT diagnosis is less efficient in distinguishing the causative pathogens of HM patients. However, CT can help distinguish fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients. Clinical Relevance Statement Our study might facilitate clinical decision-making in fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.
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Affiliation(s)
- Qian Cheng
- Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
| | - Yishu Tang
- Department of Emergency, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
| | - Jing Liu
- Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
| | - FeiYang Liu
- Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
| | - Xin Li
- Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China
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Rouvray S, Drummond RA. The role of lipids in regulating macrophage antifungal immunity. mBio 2024; 15:e0305723. [PMID: 39207168 PMCID: PMC11481918 DOI: 10.1128/mbio.03057-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024] Open
Abstract
Macrophages are critical components of the antifungal immune response. Disturbance in the number or function of these innate immune cells can significantly increase susceptibility to invasive fungal infections. Pathogenic fungi cause billions of infections every year and have an unmet clinical need, with many infections associated with unacceptably high mortality rates that primarily affect vulnerable patients with underlying immune defects. Lipid metabolism has been increasingly appreciated to significantly influence macrophage function, particularly of macrophages residing in lipid-rich organs, such as the brain, or macrophages specialized at clearing dead cells including alveolar macrophages in the lungs. In this review, we provide an overview of macrophage lipid metabolism, and discuss how lipid recycling and dysregulation affect key macrophage functions relevant for antifungal immunity including phagocytosis, functional polarization, and inflammasome activation. We focus on the fungal pathogen Cryptococcus neoformans, as this is the most common cause of death from fungal infection in humans and because several lines of evidence have already linked lipid metabolism in the regulation of C. neoformans and macrophage interactions.
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Affiliation(s)
- Sophie Rouvray
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
| | - Rebecca A. Drummond
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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Xiong C, Lu J, Chen T, Xu R. Comparison of the clinical manifestations and chest CT findings of pulmonary cryptococcosis in immunocompetent and immunocompromised patients: a systematic review and meta-analysis. BMC Pulm Med 2022; 22:415. [PMID: 36369001 PMCID: PMC9652893 DOI: 10.1186/s12890-022-02175-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 09/26/2022] [Indexed: 11/12/2022] Open
Abstract
Objective The purpose of our study was to perform a meta-analysis and systematic review to compare differences in clinical manifestations and chest computed tomography (CT) findings between immunocompetent and immunocompromised pulmonary cryptococcosis (PC) patients. Methods An extensive search for relevant studies was performed using the PubMed, EMBASE, Cochrane Library, and Web of Sciences databases from inception to September 30, 2021. We included studies that compared the clinical manifestations and chest CT findings between immunocompetent and immunocompromised PC patients. Study bias and quality assessment were performed using the Newcastle–Ottawa Scale (NOS). Results Nine studies involving 248 immunocompromised and 276 immunocompetent PC patients were included in our analysis. The NOS score of each eligible study was above 5, indicating moderate bias. The proportion of elderly patients (> = 60 years old) in the immunosuppressed group was significantly higher than that in the immunocompetent group (OR = 2.90, 95% CI (1.31–6.43), Z = 2.63, p = 0.01). Fever (OR = 7.10, 95% CI (3.84–13.12), Z = 6.25, p < 0.000) and headache (OR = 6.92, 95% CI (2.95–16.26), Z = 4.44, p < 0.000) were more common in immunosuppressed patients. According to thin-section CT findings, lesions were more frequently distributed in the upper lobe (OR = 1.90, 95% CI (1.07–3.37), Z = 2.2, p = 0.028) in immunocompromised individuals. The proportions of patients with cavity sign (OR = 5.11, 95% CI (2.96–8.83), Z = 5.86, p = 0.00), ground-glass attenuation (OR = 5.27, 95% CI (1.60–17.35), Z = 2.73, p = 0.01), and mediastinal lymph node enlargement (OR = 2.41, 95% CI (1.12–5.20), Z = 2.24, p = 0.03) were significantly higher in immunocompromised patients. Conclusion No significant differences in nonspecific respiratory symptoms were found between immunocompromised and immunocompetent PC patients. Nevertheless, fever and headache were more common in immunocompromised patients. Among the CT findings, cavity, ground-glass attenuation, and mediastinal lymph node enlargement were more common in immunocompromised individuals. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-022-02175-9.
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Wang WY, Zheng YL, Jiang LB. Cryptococcal antigen testing of lung tissue homogenate improves pulmonary cryptococcosis diagnosis: Two case reports. World J Clin Cases 2022; 10:3893-3898. [PMID: 35647158 PMCID: PMC9100706 DOI: 10.12998/wjcc.v10.i12.3893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 11/30/2021] [Accepted: 03/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pulmonary cryptococcosis (PC) is an opportunistic infectious disease of the respiratory system. Lung tissue biopsies, culture of respiratory samples (e.g., sputum, lung tissue, pleural fluid, and bronchoalveolar lavage fluid), and cryptococcal antigen (CrAg) testing are helpful for a definitive diagnosis. However, these tests are sometimes falsely negative. PC is often misdiagnosed or underdiagnosed owing to the absence of obvert symptoms, poor imaging specificity, and false-negative laboratory tests.
CASE SUMMARY We report two female patients who underwent computed tomography-guided percutaneous needle pulmonary biopsy of a lung nodule for a confirmed diagnosis. In both patients, the CrAg test on the lung biopsy tissue homogenate was positive, while the serum CrAg test was negative. Combined with the lung tissue pathology, we made the diagnosis of PC. Antifungal therapy was effective in both patients.
CONCLUSION Given the findings of our cases and the literature review, lung tissue homogenate CrAg testing can be helpful in improving the diagnosis of PC.
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Affiliation(s)
- Wei-Yi Wang
- Department of Respiratory Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
| | - Yu-Lu Zheng
- Department of Respiratory Medicine, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
| | - Li-Bin Jiang
- Department of Respiratory Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
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Li Y, Fang L, Chang FQ, Xu FZ, Zhang YB. Cryptococcus infection with asymptomatic diffuse pulmonary disease in an immunocompetent patient: A case report. World J Clin Cases 2021; 9:2619-2626. [PMID: 33889628 PMCID: PMC8040166 DOI: 10.12998/wjcc.v9.i11.2619] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 01/09/2021] [Accepted: 02/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Cryptococcus presenting as an opportunistic pathogen mainly affects immunocompromised patients, but the disseminated form of infection is rare among immunocompetent populations. The partial radiographic characteristics of pulmonary cryptococcosis mimic lung carcinoma, leading to unnecessary open chest exploratory surgery, and the lack of a gold-standard noninvasive diagnostic increases the risk of misdiagnosis. Positron emission tomography/computed tomography (PET/CT), a sensitive method for distinguishing malignant tumors, coupled with cryptococcal latex agglutination test showing a high positive rate may overcome these issues.
CASE A 36-year-old man presented for general examination, without health complaints. Routine CT showed multiple pulmonary nodules and a mass with high maximum standardized uptake value. Initially, we suspected primary malignancy with hematogenous metastasis. Although his routine fungal analysis had been negative, subsequent CT-guided percutaneous core needle biopsy and histopathology examination indicated a diagnosis of pulmonary cryptococcosis. Fluconazole (200 mg/d) antifungal drug treatment was initiated, and 1 mo later the pulmonary mass had reduced in size markedly (on chest CT scan) without any complications.
CONCLUSION Serologic and PET/CT examinations may not rule out cryptococcosis, and percutaneous lung puncture is critical under all circumstances.
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Affiliation(s)
- Yong Li
- Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
- Department of Tuberculosis, Anhui Medical University Clinical College of Chest & Anhui Chest Hospital, Hefei 230000, Anhui Province, China
| | - Lei Fang
- Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Fang-Qun Chang
- Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Fang-Zhou Xu
- Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
| | - Yan-Bei Zhang
- Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China
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Alanio A. Dormancy in Cryptococcus neoformans: 60 years of accumulating evidence. J Clin Invest 2021; 130:3353-3360. [PMID: 32484459 DOI: 10.1172/jci136223] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Cryptococcus neoformans is an opportunistic yeast that is present worldwide and interacts with various organisms. In humans, it is responsible for cryptococcosis, a deadly invasive fungal infection that represents around 220,000 cases per year worldwide. Starting from the natural history of the disease in humans, there is accumulating evidence on the capacity of this organism to enter dormancy. In response to the harsh host environment, the yeast is able to adapt dramatically and escape the vigilance of the host's immune cells to survive. Indeed, the yeast exposed to the host takes on pleiotropic phenotypes, enabling the generation of populations in heterogeneous states, including dormancy, to eventually survive at low metabolic cost and revive in favorable conditions. The concept of dormancy has been validated in C. neoformans from both epidemiological and genotyping data, and more recently from the biological point of view with the characterization of dormancy through the description of viable but nonculturable cells.
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Affiliation(s)
- Alexandre Alanio
- Laboratoire de Parasitologie-Mycologie, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.,Molecular Mycology Unit, CNRS UMR 2000, National Reference Center for Invasive Mycoses and Antifungals (NRCMA), Institut Pasteur, Paris, France.,Université de Paris, Paris, France
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Normile TG, Bryan AM, Del Poeta M. Animal Models of Cryptococcus neoformans in Identifying Immune Parameters Associated With Primary Infection and Reactivation of Latent Infection. Front Immunol 2020; 11:581750. [PMID: 33042164 PMCID: PMC7522366 DOI: 10.3389/fimmu.2020.581750] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 08/12/2020] [Indexed: 12/13/2022] Open
Abstract
Cryptococcus species are environmental fungal pathogens and the causative agents of cryptococcosis. Infection occurs upon inhalation of infectious particles, which proliferate in the lung causing a primary infection. From this primary lung infection, fungal cells can eventually disseminate to other organs, particularly the brain, causing lethal meningoencephalitis. However, in most cases, the primary infection resolves with the formation of a lung granuloma. Upon severe immunodeficiency, dormant cryptococcal cells will start proliferating in the lung granuloma and eventually will disseminate to the brain. Many investigators have sought to study the protective host immune response to this pathogen in search of host parameters that keep the proliferation of cryptococcal cells under control. The majority of the work assimilates research carried out using the primary infection animal model, mainly because a reactivation model has been available only very recently. This review will focus on anti-cryptococcal immunity in both the primary and reactivation models. An understanding of the differences in host immunity between the primary and reactivation models will help to define the key host parameters that control the infections and are important for the research and development of new therapeutic and vaccine strategies against cryptococcosis.
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Affiliation(s)
- Tyler G Normile
- Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY, United States
| | - Arielle M Bryan
- Ingenious Targeting Laboratory Incorporated, Ronkonkoma, NY, United States
| | - Maurizio Del Poeta
- Department of Microbiology and Immunology, Stony Brook University, Stony Brook, NY, United States.,Division of Infectious Diseases, School of Medicine, Stony Brook University, Stony Brook, NY, United States.,Veterans Administration Medical Center, Northport, NY, United States
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Liu X, Jia W, Huang S, Sun G. A case of pulmonary cryptococcosis with large pericardial effusion diagnosed using cervical lymph node biopsy. CLINICAL RESPIRATORY JOURNAL 2016; 12:820-823. [PMID: 27873481 DOI: 10.1111/crj.12581] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 08/21/2016] [Accepted: 11/01/2016] [Indexed: 12/21/2022]
Abstract
Pulmonary cryptococcosis (PC) is a relatively rare infectious disease. It mainly involves the lungs; however, in some patients, the infection could spread to other parts of the body. PC mostly occurs in patients with immune deficiencies. However, PC infections have been reported in non-immunocompromised patients. The diagnosis of PC is challenging in patients without immune deficiencies. Here, the case of a 27-year-old immunocompetent woman who was diagnosed with PC was report. She had unexplained fever and a history of close contact with poultry feathers. Lesions were observed in the lungs, pleural cavity, pericardium, and cervical lymph nodes. Biopsy of the cervical lymph nodes helped in the pathological diagnosis of PC. She was treated with fluconazole, and the lesions disappeared. They present this case to encourage detailed inquiry of medical history in such patients, improve the diagnostic awareness of clinicians, and help reduce the likelihood of misdiagnosis.
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Affiliation(s)
- Xuchun Liu
- Department of Respiratory Medicine, Chizhou Clinical College of Anhui Medical University, Chizhou People's Hospital, Chizhou, Anhui, 247100, China
| | - Wei Jia
- Department of Respiratory Medicine, Shanghai Integrated Traditional Chinese and Western Medicine Hospital, Shanghai, 200082, China
| | - Shubin Huang
- Department of Pathology, Chizhou Clinical College of Anhui Medical University, Chizhou People's Hospital, Chizhou, Anhui, 247100, China
| | - Gengyun Sun
- Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China
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