Delays in lumbar puncture are independently associated with mortality in cryptococcal meningitis: a nationwide study

Mansoor, Armaghan‐e‐Rehman; Thompson, Jesse; Sarwari, Arif R.

doi:10.1080/23744235.2021.1889656

Cited by 5 publications

(3 citation statements)

References 21 publications

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“…The PCA identified individual clusters that offered opportunities to structure downstream data The proportion of cases with HIV-associated CM by gender and of related survival by gender in 21 published case series. These studies include 38,485 cases with 5,834 reported deaths, which accounted for a 15.2% case fatality rate (see Supplementary Table 1 for details and references (7,9,16,26,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)). Bars show median values.…”

Section: Significant Differences In Neuroimmune Signatures In Cerebro...mentioning

confidence: 99%

“…Among studies reporting cases of CM by gender (biological sex assigned at birth), the majority of CM was diagnosed among men (2,7,9,16,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44); only four, to date, described survival by gender. Two studies done prior to optimized antiretroviral therapy (ART) initiation (delayed for 2 weeks after CM diagnosis based on the COAT Trial ( 9)) showed no differences in survival by gender (26,44).…”

Section: Introductionmentioning

confidence: 99%

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Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis

Okurut,

Boulware,

Okafor

et al. 2023

Front. Immunol.

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IntroductionSurvival among people with HIV-associated cryptococcal meningitis (CM) remains low, particularly among women, despite the currently optimal use of antifungal drugs. Cryptococcus dissemination into the central nervous system [brain, spinal cord, and cerebrospinal fluid (CSF)] elicits the local production of cytokines, chemokines, and other biomarkers. However, no consistent diagnostic or prognostic neuroimmune signature is reported to underpin the risk of death or to identify mechanisms to improve treatment and survival. We hypothesized that distinct neuroimmune signatures in the CSF would distinguish survivors from people who died on antifungal treatment and who may benefit from tailored therapy.MethodsWe considered baseline clinical features, CSF cryptococcal fungal burden, and CSF neuroimmune signatures with survival at 18 weeks among 419 consenting adults by “gender” (168 women and 251 men by biological sex defined at birth).ResultsSurvival at 18 weeks was significantly lower among women than among men {47% vs. 59%, respectively; hazard ratio (HR) = 1.4 [95% confidence interval (CI), 1.0 to 1.9; p = 0.023]}. Unsupervised principal component analysis (PCA) demonstrated divergent neuroimmune signatures by gender, survival, and intragender-specific survival. Overall, women had lower levels of programmed death ligand 1, Interleukin (IL) (IL-11RA/IL-1F30, and IL-15 (IL-15) than men (all p < 0.028). Female survivors compared with those who died expressed significant elevations in levels of CCL11 and CXCL10 chemokines (both p = 0.001), as well as increased T helper 1, regulatory, and T helper 17 cytokines (all p < 0.041). In contrast, male survivors expressed lower levels of IL-15 and IL-8 compared with men who died (p < 0.044).ConclusionsSurvivors of both genders demonstrated a significant increase in the levels of immune regulatory IL-10. In conclusion, the lower survival among women with CM was accompanied by distinct differential gender-specific neuroimmune signatures. These female and male intragender-specific survival–associated neuroimmune signatures provide potential targets for interventions to advance therapy to improve the low survival among people with HIV-associated CM.

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Section: Significant Differences In Neuroimmune Signatures In Cerebro...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis

Okurut,

Boulware,

Okafor

et al. 2023

Front. Immunol.

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“…Among studies reporting cases by gender, the majority of cryptococcal meningitis is diagnosed among males 2,7,9,19,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] . Of note, few studies to date since widespread ART rollout specifically address selective survival by gender (only five including the current study) 7 .…”

Section: Introductionmentioning

confidence: 99%

Divergent Neuroimmune Signatures in the Cerebrospinal Fluid Predict Differential Gender-Specific Survival Among Patients With HIV-Associated Cryptococcal Meningitis

Okurut

Boulware

Okafor

et al. 2023

Preprint

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Survival among people with HIV-associated cryptococcal meningitis (CM) remains low, exceptionally among women with the increased threat of death on the current optimal use of antifungal drugs. Cryptococcus dissemination into the central nervous system (CNS) prompts a neuroimmune reaction to activate pathogen-concomitant factors. However, no consistent diagnostic or prognostic immune-mediated signature is reported to underpin the risk of death or mechanism to improve treatment or survival. We theorized that the distinct neuroimmune cytokine or chemokine signatures in the cerebrospinal fluid (CSF), distinguish survivors from people who died on antifungal treatment, who may benefit from tailored therapy. We considered the baseline clinical disease features, cryptococcal microbiologic factors, and CSF neuroimmune modulated signatures among 419 consenting adults by gender (biological sex assigned at birth) (168 females and 251 males) by 18 weeks of survival on antifungal management. Survival at 18 weeks was inferior among females than males (47% vs. 59%; hazard ratio HR=1.4, 95% CI: 1.0 to 1.9, and p=0.023). Unsupervised principal component analysis (PCA) demonstrated the divergent neuroimmune signatures by gender, survival, and intragender-specific survival. Overall, females displayed lower levels of PD-L1, IL-1RA, and IL-15 than males (all p<=0.028). Female survivors compared with those who died, expressed significant fold elevations in levels of CSF (CCL11 - myeloid and CXCL10 - lymphoid chemokine (in both p=0.001), and CSF Th1, Th2, and Th17 cytokines. In contrast, male survivors expressed distinctly lower levels of CSF IL-15 and IL-8 compared with those who died. Survivors of either gender demonstrated a significant increase in the levels of immune regulatory element, IL-10. In the finale, we classified divergent neuroimmune key signatures in CSF by gender, survival, and intragender-specific survival among people with HIV-associated cryptococcal meningitis. These intragender-specific survival-associated neuroimmune signatures suggest the discrete role of gender immune regulating mechanisms as the possible targets for interventions to advance therapy to improve survival among people with HIV-associated cryptococcal meningitis.

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Management of HIV-Associated Cryptococcal Meningitis

Osborn

Spec

Mazi

2023

Curr Fungal Infect Rep

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Delays in lumbar puncture are independently associated with mortality in cryptococcal meningitis: a nationwide study

Cited by 5 publications

References 21 publications

Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis

Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis

Divergent Neuroimmune Signatures in the Cerebrospinal Fluid Predict Differential Gender-Specific Survival Among Patients With HIV-Associated Cryptococcal Meningitis

Management of HIV-Associated Cryptococcal Meningitis

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