Cerebrospinal fluid microscopy as an index for predicting the prognosis of cryptococcal meningitis patients with and without HIV

2020 ◽  
Vol 15 (17) ◽  
pp. 1645-1652
Author(s):  
Keming Zhang ◽  
Hang Li ◽  
Lei Zhang ◽  
Wanqing Liao ◽  
Liyan Ling ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Data ◽  
Cryptococcal Meningitis ◽  
Fungal Burden ◽  
Hospital Patients ◽  
Patient Prognosis ◽  
Worse Prognosis ◽  
Fluid Test

Aim: To evaluate the clinical data and quantitative cerebrospinal fluid for associations with the outcome of cryptococcal meningitis (CM) patients in the hospital. Patients & methods: We retrospectively analyzed a total of 139 CM patients comprising 108 without HIV and 31 with HIV admitted in a Jiang Xi hospital. Resμlts: We found that CM patients with the high fungal burden (≥10 yeasts/μl) (26.3%) had a worse prognosis than those with the low fungal burden (<10 yeasts/μl). (4.9%) (p = 0.0007 <0.05). Conclusion: In CM patients, a fungal burden of 10 yeasts/μl in the first cerebrospinal fluid test may be used as an indicator of patient prognosis, and we can personalize patients’ treatment based on the fungal burden to improve prognosis.

scholarly journals Flow Cytometry To Assess Cerebrospinal Fluid Fungal Burden in Cryptococcal Meningitis

2015 ◽  
Vol 54 (3) ◽  
pp. 802-804 ◽  
Author(s):  
James E. Scriven ◽  
Lisa M. Graham ◽  
Charlotte Schutz ◽  
Thomas J. Scriba ◽  
Robert J. Wilkinson ◽  
...  
Keyword(s):  
Decision Making ◽  
Flow Cytometry ◽  
Cerebrospinal Fluid ◽  
Cryptococcal Meningitis ◽  
Clinical Decision Making ◽  
Important Determinant ◽  
Clinical Decision ◽  
Fungal Burden ◽  
Rapid Technique

Fungal burden in the cerebrospinal fluid is an important determinant of mortality in cryptococcal meningitis, but its use in aiding clinical decision making is hampered by the time involved to perform quantitative cultures. Here, we demonstrate the potential of flow cytometry as a novel and rapid technique to address this issue.

scholarly journals B2M overexpression correlates with malignancy and immune signatures in human gliomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Zhang ◽  
Biqi Cui ◽  
Yulai Zhou ◽  
Xinxing Wang ◽  
Wantao Wu ◽  
...  
Keyword(s):  
Critical Role ◽  
Cell Types ◽  
Potential Candidate ◽  
Egfr Amplification ◽  
Immune Signatures ◽  
Idh Mutations ◽  
Pten Deletion ◽  
R Project ◽  
Patient Prognosis ◽  
Worse Prognosis

AbstractBecause of the limited treatment strategy of gliomas, the key of diagnosis and treatment is finding new molecular biomarkers. Here, we explored the potential of β2-microglobulin (B2M) to serve as a hopeful candidate for immunotherapy or diagnostic biomarker in gliomas. The genomic profiles, clinical characteristics, and immune signatures were analyzed based on TCGA and CGGA databases. We carried out the whole statistical analyses using R project. High B2M expression correlated with worse prognosis. Somatic mutations of gliomas with high B2M expression are associated with PTEN deletion and EGFR amplification. Isocitrate dehydrogenase (IDH) mutations accounted for 82% in gliomas with low B2M expression. In addition, B2M positively correlated with ESTIMATE scores, interacted with infiltrating immune and stromal cell types. B2M also suppressed anti-tumor immunity through immune related processes. Meanwhile, B2M was associated with immune checkpoint molecules and inflammatory activities. Finally, functional annotation of the identified B2M related genes verified that B2M was a potential candidate for immunotherapy. We confirmed that B2M played a critical role in tumor progression, patient prognosis and immunotherapy of gliomas.

scholarly journals Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Melissa A. Rolfes ◽  
Joshua Rhein ◽  
Charlotte Schutz ◽  
Kabanda Taseera ◽  
Henry W. Nabeta ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Clinical Outcomes ◽  
Antifungal Therapy ◽  
Induction Therapy ◽  
Cryptococcal Meningitis ◽  
Cox Regression ◽  
Culture Positivity ◽  
Immunodeficiency Virus ◽  
Cerebrospinal Fluid Culture

Abstract Background.  Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%–50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods.  Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7–1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by “enhanced consolidation” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1–2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results.  Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6–2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions.  Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes.

scholarly journals Pharmacodynamics of Isavuconazole in a Rabbit Model of Cryptococcal Meningoencephalitis

2019 ◽  
Vol 63 (9) ◽  
Author(s):  
Laura L. Kovanda ◽  
Charles Giamberardino ◽  
Laura McEntee ◽  
Dena L. Toffaletti ◽  
Kelly S. Franke ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Fungal Pathogens ◽  
Rabbit Model ◽  
Response Relationship ◽  
Fungal Burden ◽  
Cryptococcal Meningoencephalitis ◽  
Exposure Response ◽  
Dose Dependent ◽  
The Brain ◽  
Over Time

ABSTRACT Cryptococcus spp., important fungal pathogens, are the leading cause of fungus-related mortality in human immunodeficiency virus-infected patients, and new therapeutic options are desperately needed. Isavuconazonium sulfate, a newer triazole antifungal agent, was studied to characterize the exposure-response relationship in a rabbit model of cryptococcal meningoencephalitis. Rabbits treated with isavuconazonium sulfate were compared with those treated with fluconazole and untreated controls. The fungal burden in the cerebrospinal fluid was measured serially over time, while the yeast concentrations in the brain and the eye (aqueous humor) were determined at the end of therapy. The exposure impact of isavuconazonium sulfate dosing in the rabbit was linked using mathematical modeling. Similar significant reductions in the fungal burden in the brain and cerebrospinal fluid in rabbits treated with isavuconazonium sulfate and fluconazole compared with that in the untreated controls were observed. No dose-dependent response was demonstrated with isavuconazonium sulfate treatment in this study. The treatment of cryptococcal meningoencephalitis with isavuconazonium sulfate was similar to that with fluconazole. Dose-dependent reductions in yeast over time were not demonstrated, which limited our ability to estimate the pharmacodynamic target. Further nonclinical and clinical studies are needed in order to characterize the extent of the exposure-response relationship in cryptococcal meningoencephalitis. However, this study suggests that isavuconazonium sulfate, like fluconazole, could be beneficial in the setting of consolidation and maintenance therapy, rather than induction monotherapy, in high-burden cryptococcal meningoencephalitis.

scholarly journals Cerebrospinal Fluid HIV-1 Viral Load During Treatment of Cryptococcal Meningitis

2010 ◽  
Vol 53 (5) ◽  
pp. 668-669 ◽  
Author(s):  
Annemarie E Brouwer ◽  
Praprit Teparrukkul ◽  
Adul Rajanuwong ◽  
Wirongrong Chierakul ◽  
Weera Mahavanakul ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Viral Load ◽  
Cryptococcal Meningitis ◽  
Hiv 1

scholarly journals LATERAL FLOW ASSAY FOR CRYPTOCOCCAL ANTIGEN: AN IMPORTANT ADVANCE TO IMPROVE THE CONTINUUM OF HIV CARE AND REDUCE CRYPTOCOCCAL MENINGITIS-RELATED MORTALITY

2015 ◽  
Vol 57 (suppl 19) ◽  
pp. 38-45 ◽  
Author(s):  
Jose E. VIDAL ◽  
David R. BOULWARE
Keyword(s):  
Cerebrospinal Fluid ◽  
Cryptococcal Meningitis ◽  
Capsular Polysaccharide ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
World Health ◽  
Hiv Care ◽  
Analytical Sensitivity ◽  
Symptomatic Infection ◽  
Cryptococcal Antigen

SUMMARYAIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex) or enzyme-linked immunoassay (EIA) has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA) was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipment-free, and Delivered). CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcusspecies. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/mL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die.

scholarly journals Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial

2015 ◽  
Vol 212 (5) ◽  
pp. 769-778 ◽  
Author(s):  
James E. Scriven ◽  
Joshua Rhein ◽  
Katherine Huppler Hullsiek ◽  
Maximilian von Hohenberg ◽  
Grace Linder ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Randomized Trial ◽  
Cryptococcal Meningitis ◽  
Macrophage Activation ◽  
Cerebrospinal Fluid Pleocytosis

Unique clinical features of cryptococcal meningitis among Chinese patients without predisposing diseases against patients with predisposing diseases

2019 ◽  
Vol 57 (8) ◽  
pp. 944-953 ◽  
Author(s):  
Lijun Xu ◽  
Xinyue Zhang ◽  
Yongzheng Guo ◽  
Ran Tao ◽  
Xiahong Dai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Serum Albumin ◽  
Amphotericin B ◽  
Clinical Features ◽  
Cryptococcal Meningitis ◽  
White Blood Cells ◽  
Chinese Patients ◽  
Fungal Burden ◽  
Risk Of Death ◽  
Culture Positivity

Abstract The clinical features of cryptococcal meningitis (CM) in patients without predisposing diseases (PD) remain unclear. In sum, 162 of the 167 patients without PD and 162 of the 309 patients with PD were enrolled after propensity score matching. Demographic characteristics, symptoms, blood, and cerebrospinal fluid (CSF) characteristics were compared between the two groups. Kaplan-Meier curves and a Cox proportional hazards model were used to assess the factors associated with 10-week mortality. In total, approximately 35.1% of CM patients were without PD. CM patients without PD had blood profiles of higher white blood cells (WBC) [8.9(6.7–11.0) × 109/l], hemoglobin (128.4 ± 20.9 g/l), platelets [(226.2 ± 64.1) × 109/l], and serum albumin (41.2 ± 5.8 g/l) (all P ≤ .001) and CSF profiles of lower glucose (2.0 ± 1.2 mmol/l), pleocytosis [65.0 (18.0–160.0) × 106/l] and higher total protein [0.9 (0.7–1.4)g/l] (all P < .05). CM patients without PD had lower Cryptococcus culture positivity in CSF (62.5% vs. 74.1%, P = .039) but higher 2-week of CSF culture sterilization rates (69.4% vs. 51.3%, P = .031). The overall 10-week survival rate was 84.7% in patients without PD and 81.1% in patients with PD (Log-rank P = .439). CSF glucose <1.5 mmol/l, CSF fungal burden >20 cells/high power field and treatment lacking amphotericin B had a 3–4 times higher risk of death in patients without PD, whereas serum albumin <35 g/l, CSF glucose < 1.5 mmol/l, and CSF WBC <55 × 106 cell/l were risk factors for patients with PD. CM patients without PD had unique blood and CSF profiles, especially, had lower Cryptococcus culture positivity in CSF, and higher 2-week CSF culture sterilization. Low CSF glucose levels, higher fungal burden, and treatment without amphotericin B were risk factors for 10-week mortality.

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