Utility of clinical assessment, imaging, and cryptococcal antigen titer to predict AIDS-related complicated forms of cryptococcal meningitis.

BACKGROUND: This study aimed to evaluate the prevalence and predictors of AIDS-related complicated cryptococcal meningitis. The outcome was complicated cryptococcal meningitis: prolonged (>/= 14 days) altered mental status, persistent (>/= 14 days) focal neurologic findings, cerebrospinal fluid (CSF) shunt placement or death. Predictor variable operating characteristics were estimated using receiver operating characteristic curve (ROC) analysis. Multivariate analysis identified independent predictors of the outcome. RESULTS: From 1990-2009, 82 patients with first episode of cryptococcal meningitis were identified. Of these, 14 (17%) met criteria for complicated forms of cryptococcal meningitis (prolonged altered mental status 6, persistent focal neurologic findings 7, CSF surgical shunt placement 8, and death 5). Patients with complicated cryptococcal meningitis had higher frequency of baseline focal neurological findings, head computed tomography (CT) abnormalities, mean CSF opening pressure, and cryptococcal antigen (CRAG) titers in serum and CSF. ROC area of log2 serum and CSF CRAG titers to predict complicated forms of cryptococcal meningitis were comparable, 0.78 (95%CI: 0.66 to 0.90) vs. 0.78 (95% CI: 0.67 to 0.89), respectively (chi2, p = 0.95). The ROC areas to predict the outcomes were similar for CSF pressure and CSF CRAG titers. In a multiple logistic regression model, the following were significant predictors of the outcome: baseline focal neurologic findings, head CT abnormalities and log2 CSF CRAG titer. CONCLUSIONS: During initial clinical evaluation, a focal neurologic exam, abnormal head CT and large cryptococcal burden measured by CRAG titer are associated with the outcome of complicated cryptococcal meningitis following 2 weeks from antifungal therapy initiation.

Factor XI deficiency in Southern Iran: identification of a novel missense mutation.

Factor XI (FXI)-deficiency is a rare coagulation disorder inherited as an autosomal recessive trait, which is most common in Ashkenazi Jews, but also found in other groups like Moslems. We have reviewed for the first time cases of FXI deficiency in southern Iran in order to analyze their mutations related to factor XI, the main clinical and biological features, levels of circulating factor XI, and bleeding history. All 15 exons and exon-intron boundaries of F11 were polymerase chain reaction amplified using sets of primers designed on the basis of the known genomic sequence of the gene. Among bleeding disorder cases, five were FXI-deficient. FXI clotting activity ranged 0.39-16%. All were severely deficient. In all analyzed patients, functional level of FXI was markedly reduced, confirming the diagnosis of quantitative FXI deficiency. Sequencing of F11 identified three mutations: (1) a highly prevalent type II nonsense mutation (Glu117stop) in a homozygous patient, (2) a previously reported missense (Glu547Lys), and (3) novel missense (Gly372Ala) mutation. No causative mutation was found in the sequenced regions of other patients. One novel mutation and two previously described mutations were identified in patients living in southern Iran. No recurrent mutation was found, perhaps because there is a more intense population mixing in southern Iran. Screening a higher number of FXI-deficient patients will also be necessary to reveal the existence of a founder effect for these mutations in the Iranian population.