Purpose. Serum cytokines/chemokines play important roles in cryptococcal meningitis, but it is unclear whether cytokines/chemokines in cerebrospinal fluid (CSF) contribute to high intracranial pressure (HICP) in HIV-associated cryptococcal meningitis (HCM). Methods. CSF cytokines/chemokines were assayed in 17 HIV-uninfected patients, 26 HIV-infected patients without CNS infection, and 39 HCM patients at admission. Principal component analysis and correlation and logistic regression analyses were used to assess the relationships between these parameters. Results. The CSF Th1, Th2, and macrophage cytokines showed an obvious increase in HCM patients as compared to the HIV-uninfected patients and HIV-infected patients without CNS infection. CSF IL-6, GM-CSF, and IL-8 were positively correlated with CSF fungal burden. Serum CD4 count, CSF Th1 cytokines (TNF-α, TNF-β, IL-12, IL-1β, and INF-α2), and Th2 cytokines (IL-5 and IL-6) were closely related to cryptococcal meningitis. Furthermore, both Th1 cytokines (TNF-α, TNF-β, INF-γ, and IL-12) and Th2 cytokines (IL-4 and IL-10) contribute to HICP. Conclusion. Overall, the present findings indicated that both pro- and anti-inflammatory cytokines of Th1, Th2, and macrophage origin contributed to the development of HCM. Specifically, the chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance and reduced CD4 count were found to be important contributors to HICP. Summary. Our research suggested that chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance in HIV-infected patients played more important role than Cryptococcus numbers and size in CSF on the development of high intracranial pressure in HIV-associated cryptococcal meningitis, providing a new understanding of mechanisms of HCM.

To evaluate whether the serum sodium concentration is associated with the progression and long-term prognosis of Chinese HIV/AIDS patients. Three hundred and eighty seven hospitalized patients were recruited into this retrospective cohort study. The strata of serum sodium concentration were moderate/severe hyponatremia, mild hyponatremia and normonatremia. Disease progression was estimated using CD4 counts and the WHO clinical stage. Correlation analysis was used to evaluate the serum sodium concentration with disease progression. The Kaplan-Meier method and the Cox proportional hazards model were used to analyze the effect of different serum sodium levels on survival. In this study 206 patients (53.2%) had hyponatremia, including 10.6% patients with moderate/severe hyponatremia and 42.6% with mild hyponatremia. The serum sodium concentration was significantly correlated with the HIV/AIDS progression (P<0.001). During the follow-up, 100 patients (25.6%) died. The cumulative survival rates of HIV/AIDS patients were 47.8%±8.5% in patients with moderate/severe hyponatremia, 59.8%±5.0% with mild hyponatremia and 79.9%±3.4% with normonatremia (log-rank P<0.001). After adjusting for sex, age, WHO stage, CD4 count, hemoglobin and albumin, the relative hazard was 3.5 (95% CI: 1.9–6.5) for patients with moderate/severe hyponatremia (P<0.001), and 1.5 (95% CI: 0.9–2.4) for those with mild hyponatremia (P = 0.161), compared with normonatremic patients. The serum sodium level is closely correlated with the severity of patients. Only moderate/severe hyponatremia affects the prognosis of Chinese HIV/AIDS patients. Earlier intensive medical managements(including HAART)are necessary to increase the survival rates of Chinese HIV/AIDS patients with moderate/severe hyponatremia.

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 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.

Background: The influence of Amphotericin B (AmB) dose and the addition of fluconazole (Flu) on the AmB + 5-flucytosine (5FC) regimen for cryptococcal meningitis (CM) treatment remain debatable. Methods: A retrospective study was conducted to compare 44 CM patients treated with AmB + 5FC and 78 CM patients treated with AmB + 5FC + Flu using the propensity score matching method. The effects of AmB dosage, AmB course and Flu addition on the cerebrospinal fluid (CSF) chemical profile recovery, adverse effects, and 90-day mortality were compared between the groups. Results: No differences in adverse effects, the rate of the 14-day CSF chemical profile recovery and 90-day cumulative survival rate (91.2% vs. 87.5%, P = 0.637) were observed between the AmB + 5FC group and the AmB + 5FC + Flu group. However, the incidence rates of hypokalemia (33.9%) and creatinine elevation (7.1%) in patients treated with an AmB dosage of 0.4–0.5 mg/kg/d were less than those (53.0 and 22.7%, respectively) treated with an AmB dosage of 0.6–0.7 mg/kg/d (P = 0.034 and P = 0.018, respectively). The 90-day cumulative survival rate was 70.1% for patients treated with AmB for <14 days and 96.4% for patients treated with AmB for ≥14 days (log-rank P < 0.001). Multivariate Cox proportional hazards models suggested the hazard ratio was 26.8 (95% CI: 3.9–183.2) for patients treated with AmB < 14 days than those treated with AmB ≥ 14 days (P = 0.001). Conclusion: Treatment with AmB less than 14 days was associated with a higher 90-day mortality in CM patients. A relative lower dosage but prolonged course of AmB in the +5FC ± Flu regimen led to favorable trends of fewer adverse effects and comparable clinical efficacy.