Repurposing leflunomide for relapsed/refractory multiple myeloma: a phase 1 study.

The inexpensive, well-tolerated, immunomodulatory agent leflunomide, used extensively for the treatment of rheumatoid arthritis, has been shown to produce significant activity against multiple myeloma (MM) in pre-clinical studies. We conducted a phase 1 study (clinicaltrials.gov: NCT02509052) of single agent leflunomide in patients with relapsed/refractory MM (≥3 prior therapies).

Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma.

Objective: A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective.

Methods: Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6).

Gene expression patterns of dengue virus-infected children from nicaragua reveal a distinct signature of increased metabolism.

Background: Infection with dengue viruses (DENV) leads to a spectrum of disease outcomes. The pathophysiology of severe versus non-severe manifestations of DENV infection may be driven by host responses, which could be reflected in the transcriptional profiles of peripheral blood immune cells.

Methodology/principal Findings: We conducted genome-wide microarray analysis of whole blood RNA from 34 DENV-infected children in Nicaragua collected on days 3-6 of illness, with different disease manifestations.

Trends in patterns of dengue transmission over 4 years in a pediatric cohort study in Nicaragua.

Background: Dengue is the most prevalent mosquito-borne viral disease in humans and a major urban public health problem worldwide.

Methods: A prospective cohort study of approximately 3800 children initially aged 2-9 years was established in Managua, Nicaragua, in 2004 to study the natural history of dengue transmission in an urban pediatric population. Blood samples from healthy subjects were collected annually prior to the dengue season, and identification of dengue cases occurred via enhanced passive surveillance at the study health center.

Improvement in hospital indicators after changes in dengue case management in Nicaragua.

Dengue is a major problem worldwide, and improving case management is a significant priority. In consultation with colleagues in Thailand, changes in management of hospitalized dengue cases were introduced in Nicaragua, including oral rather than intravenous (IV) fluids upon admission, continuous monitoring of clinical and laboratory signs, and use of IV fluids principally during the critical phase and colloids in management of shock. Two periods were compared, before (2003) and after (2005) their implementation, to assess impact.

The Nicaraguan pediatric dengue cohort study: study design, methods, use of information technology, and extension to other infectious diseases.

Dengue is a mosquito-borne viral disease that is a major public health problem worldwide. In 2004, the Pediatric Dengue Cohort Study was established in Managua, Nicaragua, to study the natural history and transmission of dengue in children. Here, the authors describe the study design, methods, and results from 2004 to 2008.

Evaluation of immunological markers in serum, filter-paper blood spots, and saliva for dengue diagnosis and epidemiological studies.

Background: Numerous immunological approaches exist to diagnose dengue or detect dengue virus (DENV) infections.

Objectives: To determine the best immunological markers and specimen types for dengue diagnosis and for measuring incidence of DENV infection in community-based studies.

Study Design: In one study, acute- and convalescent-phase samples were collected from hospitalized suspected pediatric dengue cases in Managua, Nicaragua, from September 2003 to February 2004.

Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever.

In vitro studies have attempted to identify dengue virus (DEN) target cells in peripheral blood; however, extensive phenotyping of peripheral blood mononuclear cells (PBMCs) from dengue patients has not been reported. PBMCs collected from hospitalized children suspected of acute dengue were analyzed for DEN prM, CD32, CD86, CD14, CD11c, CD16, CD209, CCR7, CD4, and CD8 by flow cytometry to detect DEN antigen in PBMCs and to phenotype DEN-positive cells. DEN prM was detected primarily in activated monocytes (CD14(+), CD32(+), CD86(+), CD11c(+)).

High seroprevalence of antibodies against dengue virus in a prospective study of schoolchildren in Managua, Nicaragua.

To investigate the incidence of dengue virus (DENV) infection in Nicaragua, a 2-year prospective study was conducted in schoolchildren 4-16 years old in the capital city of Managua. Blood samples were collected before the rainy season in 2001, 2002 and 2003, and were assayed for DENV-specific antibodies. Participants were monitored for dengue-like illness, and acute and convalescent blood samples were collected from suspected dengue cases.

Serotype-specific differences in clinical manifestations of dengue.

Dengue, the most prevalent arthropod-borne viral disease of humans, is caused by four serotypes of dengue virus (DENV 1-4). Although all four DENV serotypes cause a range of illness, defining precisely which clinical characteristics are associated with the distinct serotypes has been elusive. A cross-sectional study was conducted on 984 and 313 hospitalized children with confirmed DENV infections during two time periods, respectively, in the same hospitals in Nicaragua: a 3-year period (1999-2001) when DENV-2 accounted for 96% of the viruses identified, and the 2003 dengue season when DENV-1 predominated (87% of identified serotypes).

Differences in dengue severity in infants, children, and adults in a 3-year hospital-based study in Nicaragua.

To investigate age-related differences in dengue severity, 114 infants, 1,211 children, and 346 adults with laboratory-confirmed dengue virus (DEN) infections presenting to three hospitals in major urban centers in Nicaragua were recruited from 1999 to 2001. The age distribution of dengue cases and the circulating serotype (predominantly DEN2) were representative of national data. Similar results were obtained when either dengue hemorrhagic fever/dengue shock syndrome or its principal manifestations (vascular permeability, internal hemorrhage, marked thrombocytopenia, and/or shock) were analyzed in relation to age and immune status.

Short report: assessment of the World Health Organization scheme for classification of dengue severity in Nicaragua.

The World Health Organization (WHO) scheme for classification of dengue severity was evaluated in a three-year study of 1,671 confirmed dengue cases in three Nicaraguan hospitals. The WHO classification of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) was compared with the presence of hemorrhagic manifestations, signs of vascular permeability, marked thrombocytopenia, and shock in 114 infants, 1,211 children, and 346 adults. We found that strict application of the WHO criteria fails to detect a significant number of patients with severe manifestations of dengue, especially in adults.

Sequential immunization with vesicles prepared from heterologous Neisseria meningitidis strains elicits broadly protective serum antibodies to group B strains.

The capsular polysaccharide of Neisseria meningitidis group B is an autoantigen, whereas noncapsular antigens are highly variable. These factors present formidable challenges for development of a broadly protective and safe group B vaccine. Mice and guinea pigs were sequentially immunized with three doses of micovesicles or outer membrane vesicles prepared from three meningococcal strains that were each antigenically heterologous with respect to the two major porin proteins, PorA and PorB, and the group capsular polysaccharide.