Liposomal cytarabine (DepoCyte®) for the treatment of neoplastic meningitis

Neoplastic meningitis is a feared complication in cancer patients, the median survival ranging from some weeks to a few months. Management is palliative and aims to provide symptoms relief while delaying neurological deterioration. Intrathecal methotrexate and/or cytarabine is the most widely used treatment in such clinical situations. These drugs are administered 2 or 5 times a week— a circumstance that is both bothersome for the patient and time-costly for the medical personnel. Liposomal cytarabine is a sustained-release cytarabine formulation specifically developed for the treatment of neoplastic meningitis. Its administration on a twice-weekly basis ensures sustained cytotoxic drug concentrations in cerebrospinal fluid. Controlled clinical trials have shown liposomal cytarabine to be equally or more effective than the classical treatment for neoplastic meningitis. In lymphomatous meningitis, liposomal cytarabine offers superior response rates, improved patient quality of life, and a prolongation of the time to neurological progression. When the cause of meningitis is a solid tumor, liposomal cytarabine prolongs the time to neurological progression and improves quality of life. These observations indicate that DepoCyte^®, is a convenient treatment for patients with neoplastic meningitis, due to its efficacy and easy of administration characteristics.     

HIV infection-related premature immunosenescence: high rates of immune exhaustion after short time of infection

Premature immunosenescence has been reported in different HIV scenarios. However, how premature is the HIV-related immunosenescent phenotype is still unknown. Thus, the aim of this study was to analyze the immunosenescent status of young viraemic naive HIV-infected individuals, with less than four years from infection. To this end, replicative senescence, activation and proliferation T-cell levels were analyzed in chronically HIV-infected young individuals and both, elderly and young healthy controls. We show that young HIV-infected viraemic patients, with less than four years from infection, have early immune exhaustion leading to a premature immunosenescence comparable to healthy people 40 years elder. In addition, memory T-cell subsets showed greater alterations than elder healthy controls and, in patients with high viral loads, CD57 expression at the memory T-cell subsets was correlated with lower viral increases but higher CD4 T-cell lost during follow up.     

Improved viral suppression after treatment optimization in HIV-infected patients with persistent low-level viremia

Optimizing treatment for patients with persistent low-level viremia is complicated because most genotyping tests are validated for viral loads >1000 copies per milliliter. In this study, genotypes of 92 treatment-experienced patients with persistent low-level viremia were determined using an in-house assay. Based on the resistance profiles obtained from genotyping and patient pharmacologic history, patients were either maintained on their antiviral regimen (n = 51) or received an optimized regimen (n = 41). In the group receiving optimized treatment, undetectable viral loads were achieved in 73.2% at 6 months and at 90.2% at 1 year, indicating that treatment guided by genotyping of patients with low-level viremia is effective in achieving viral suppression.     

Impact of the peginterferon‐α 2a and ribavirin plasma levels on viral kinetics and sustained virological response in genotype 1 HCV/HIV‐co‐infected patients with the unfavourable non‐CC IL28B genotypes

Studies on the association between the peginterferon‐α and ribavirin levels and sustained virological response (SVR) have shown yielded conflicting results, but most of them were performed before the influence of IL28B polymorphisms was known. Our aim was to assess the effects of peginterferon‐α 2a and ribavirin plasma levels on viral kinetics and SVR in hepatitis C virus genotype 1 HCV‐1/HIV‐co‐infected patients according to IL28B genotype. This was a cohort study of HCV‐1/HIV‐co‐infected patients who were HCV‐treatment naïve and for whom the efficacy of peginterferon‐α 2a plus ribavirin was evaluated by per‐protocol analysis. The peginterferon‐α 2a and ribavirin levels were measured by ELISA and HPLC‐UV, respectively. The relationships among host and viral factors, the trough drugs levels and virological responses were analysed by multivariate regression analyses. A total of 131 Caucasian patients were included (cirrhosis:38.9%). Overall, SVR rate was 39.6%. In patients with CC IL28B genotype, SVR was related neither to peginterferon‐α 2a nor to ribavirin plasma levels, while higher levels of both drugs were the only variables independently associated with SVR in individuals with CT/TT IL28B genotypes (OR, 5.02; CI₉₅, 1.45–17.1; P = 0.001 and 4.0; CI₉₅, 1.08–14.7; P = 0.038, respectively). Moreover, faster viral declines were observed in CT/TT patients when pegIFN‐α 2a and ribavirin plasma levels were greater than 3400 pg/mL and 1.6 μg/mL, respectively. In contrast to the results for CC patients, the results in patients carrying the unfavourable CT/TT IL28B genotypes showed that plasma levels of both drugs have significant effects on viral kinetics and SVR.     

The sixth international RASopathies symposium: Precision medicine—From promise to practice

The RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS‐mitogen activated protein kinase (MAPK) pathway genes. RASopathies share RAS/MAPK pathway dysregulation and share phenotypic manifestations affecting numerous organ systems, causing lifelong and at times life‐limiting medical complications. RASopathies may benefit from precision medicine approaches. For this reason, the Sixth International RASopathies Symposium focused on exploring precision medicine. This meeting brought together basic science researchers, clinicians, clinician scientists, patient advocates, and representatives from pharmaceutical companies and the National Institutes of Health. Novel RASopathy genes, variants, and animal models were discussed in the context of medication trials and drug development. Attempts to define and measure meaningful endpoints for treatment trials were discussed, as was drug availability to patients after trial completion.     

Prospective evaluation of fever of unknown origin in patients infected with the human immunodeficiency virus

The aim of this study was to determine the frequency and aetiology of fever of unknown origin (FUO) in patients infected with the human immunodeficiency virus (HIV), to assess the value of the tests used in its diagnosis, and to evaluate possible models of diagnosis for the causes found most frequently. One hundred twenty-eight (3.5%) of 3603 hospitalised HIV-positive patients evaluated from October 1992 to December 1993 had FUO, defined by established criteria. Eighty-six percent of patients with FUO had previously progressed to AIDS. The median CD4+ cell count was 46/mm³. A definite diagnosis was made in 96 (75%) of the 128 patients and a possible diagnosis in 24 (18.7%), whilst no diagnosis was made in eight cases (6.2%). Tuberculosis (48.3%), visceral leishmaniasis (16%), and infection byMycobacterium avium complex (6.9%) were the diseases found most frequently. The most useful diagnostic tests were liver biopsy (68.9%) and bone marrow aspirate/biopsy (39.7%). It is not possible to predict clinically the cases of FUO due to tuberculosis, whilst thrombocytopaenia < 100,000 cells/mm³ alone is useful for differentiating the cases of visceral leishmaniasis, with a negative predictive value of 95.2%.