Fulminant onset of acute leukemia from normal hematopoiesis within 3 months of follow up for multiple myeloma treated with total therapy protocols.

Assiduous surveillance for genetic aberrations is necessary in patients on cytotoxic therapies to detect therapy-related myeloid neoplasms (t-MN). Current modalities include metaphase cytogenetics and FISH. Since t-MN may develop abruptly in cytogenetically normal patients, a discussion exploring additional methods such as SNP-array and targeted-deep-sequencing to detect subchromosomal abnormalities is needed.

Patterns of total cost and economic consequences of progression for patients with newly diagnosed multiple myeloma.

Background: Few studies have addressed the cost patterns of patients with multiple myeloma (MM) before and after first relapse. This US claims analysis evaluated, from a US health plan perspective, patterns of total direct costs of care from treatment initiation to progression for patients with MM treated with novel agents, using time to next therapy (TTNT) as a proxy measure for progression.

Methods: A retrospective study was conducted using a large US claims database, evaluating patients with claims for MM between 2006 and 2013.

CXC chemokine ligand 12a enhances chondrocyte proliferation and maturation during endochondral bone formation.

Objective: We investigated the roles of CXC chemokine ligand 12a (CXCL12a), also known as stromal cell-derived factor-1α (SDF-1α), in endochondral bone growth, which can give us important clues to understand the role of CXCL12a in osteoarthritis (OA).

Methods: Primary chondrocytes and tibial explants from embryonic 15.5 day-old mice were cultured with recombinant mouse CXCL12a.

Renal insufficiency retains adverse prognostic implications despite renal function improvement following Total Therapy for newly diagnosed multiple myeloma.

Renal insufficiency (RI) is a frequent complication of multiple myeloma (MM) with negative consequences for patient survival. The improved clinical outcome with successive Total Therapy (TT) protocols was limited to patients without RI. We therefore performed a retrospective analysis of overall survival, progression-free survival and time to progression (TTP) of patients enrolled in TT2 and TT3 in relationship to RI present at baseline and pre-transplant.

Role of magnetic resonance imaging in the management of patients with multiple myeloma: a consensus statement.

Purpose: The aim of International Myeloma Working Group was to develop practical recommendations for the use of magnetic resonance imaging (MRI) in multiple myeloma (MM).

Methods: An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations for the value of MRI based on data published through March 2014.

Recommendations: MRI has high sensitivity for the early detection of marrow infiltration by myeloma cells compared with other radiographic methods.

Nef proteins of epidemic HIV-1 group O strains antagonize human tetherin.

Most simian immunodeficiency viruses use their Nef protein to antagonize the host restriction factor tetherin. A deletion in human tetherin confers Nef resistance, representing a hurdle to successful zoonotic transmission. HIV-1 group M evolved to utilize the viral protein U (Vpu) to counteract tetherin.

Lentiviral Nef proteins manipulate T cells in a subset-specific manner.

Unlabelled: The role of the accessory viral Nef protein as a multifunctional manipulator of the host cell that is required for effective replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) in vivo is well established. It is unknown, however, whether Nef manipulates all or just specific subsets of CD4(+) T cells, which are the main targets of virus infection and differ substantially in their state of activation and importance for a functional immune system. Here, we analyzed the effect of Nef proteins differing in their T cell receptor (TCR)-CD3 downmodulation function in HIV-infected human lymphoid aggregate cultures and peripheral blood mononuclear cells.

Novel drug combinations for the management of relapsed/refractory multiple myeloma.

The outcomes and management of multiple myeloma (MM) in the United States have changed dramatically over the past 15 years with the approval by the US Food and Drug Administration (FDA) of 6 new drugs (thalidomide, lenalidomide, bortezomib, pegylated liposomal doxorubicin [Doxil], carfilzomib, and pomalidomide). Despite these advances, a majority of patients with MM relapse, requiring subsequent lines of therapy to manage their disease as a chronic condition. Even though oncologists recognize the heterogeneity in the biology and clinical presentation of patients with newly diagnosed MM, clinical investigations still approach MM in a one-size-fits-all manner.

International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.

This International Myeloma Working Group consensus updates the disease definition of multiple myeloma to include validated biomarkers in addition to existing requirements of attributable CRAB features (hypercalcaemia, renal failure, anaemia, and bone lesions). These changes are based on the identification of biomarkers associated with near inevitable development of CRAB features in patients who would otherwise be regarded as having smouldering multiple myeloma. A delay in application of the label of multiple myeloma and postponement of therapy could be detrimental to these patients.

Chronic Recurrent Multifocal Osteomyelitis in Children: A Multidisciplinary Approach is needed to establish a Diagnosis.

Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory disease of unknown cause. In general, CRMO follows a characteristic clinical course and is regarded at present as a distinct entity. It affects bone and occurs predominantly in children and adolescents.

In silico modeling predicts drug sensitivity of patient-derived cancer cells.

Background: Glioblastoma (GBM) is an aggressive disease associated with poor survival. It is essential to account for the complexity of GBM biology to improve diagnostic and therapeutic strategies. This complexity is best represented by the increasing amounts of profiling ("omics") data available due to advances in biotechnology.

Follow up for emergency department patients after intravenous contrast and risk of nephropathy.

Introduction: Contrast-induced nephropathy (CIN), defined as an increase in serum creatinine (SCr) greater than 25% or ≥0.5 mg/dL within 3 days of intravenous (IV) contrast administration in the absence of an alternative cause, is the third most common cause of new acute renal failure in hospitalized patients. It is known to increase in-hospital mortality up to 27%.

Liquefaction of semen generates and later degrades a conserved semenogelin peptide that enhances HIV infection.

Unlabelled: Semen enhances HIV infection in vitro, but how long it retains this activity has not been carefully examined. Immediately postejaculation, semen exists as a semisolid coagulum, which then converts to a more liquid form in a process termed liquefaction. We demonstrate that early during liquefaction, semen exhibits maximal HIV-enhancing activity that gradually declines upon further incubation.

Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen.

Naturally occurring fragments of the abundant semen proteins prostatic acid phosphatase (PAP) and semenogelins form amyloid fibrils in vitro. These fibrils boost HIV infection and may play a key role in the spread of the AIDS pandemic. However, the presence of amyloid fibrils in semen remained to be demonstrated.

Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data.

Background: Lenalidomide has been linked to second primary malignancies in myeloma. We aimed to pool and analyse available data to compare the incidence of second primary malignancies in patients with and without lenalidomide exposure.

Methods: We identified relevant studies through a search of PubMed and abstracts from the American Society of Clinical Oncology, American Society of Hematology, and the International Myeloma Workshop.

Jumping translocations of 1q12 in multiple myeloma: a novel mechanism for deletion of 17p in cytogenetically defined high-risk disease.

Multiple myeloma (MM) is a B-cell malignancy driven in part by increasing copy number alterations (CNAs) during disease progression. Prognostically significant CNAs accumulate during clonal evolution and include gains of 1q21 and deletions of 17p, among others. Unfortunately, the mechanisms underlying the accumulation of CNAs and resulting subclonal heterogeneity in high-risk MM are poorly understood.

Management of relapses after hematopoietic cell transplantation in T-cell non-Hodgkin lymphomas.

T-cell non-Hodgkin lymphomas (NHLs) are a heterogeneous group of malignancies that represent 10%-15% of all NHLs. The prognosis of relapsed T-cell NHL is poor, especially for those relapsing after an autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT). Disease relapse post auto-HCT is best managed on a clinical trial.

How long can we let the myeloma smolder?

Smoldering or asymptomatic multiple myeloma may be best described as a state of limbo where the patient has not developed any symptoms of disease and is being observed expectantly. With the advent of novel agents in myeloma therapy, several clinical investigations are underway to determine whether early intervention will help improve survival outcomes in this patient population. Mateos MV et al.

Patterns of central nervous system involvement in relapsed and refractory multiple myeloma.

Background: Invasion of CNS in MM is an extremely rare occurrence that is associated with advanced disease with poor prognosis.

Patients And Methods: Our MM database identified 35 CNS MM cases presenting between January 1996 and March 2012. Descriptive analyses were performed on available data on patient characteristics, disease course, and outcomes.

Analysis of CD34+ cell collection using two mobilization regimens for newly diagnosed multiple myeloma patients reveals the separate impact of mobilization and collection variables.

Mobilization regimens for CD34+ cells have generally been judged successful based on the number of cells collected without evaluating mobilization separately from collection. Using retrospective data for patients who collected CD34+ cells on Total Therapy protocols 3a/3b (VTD-PACE) and Total Therapy 4/5 using a novel regimen that added low dose melphalan to VTD-PACE (MVTD-PACE), we analyzed mobilization and collection variables separately. A significant difference favoring MVDT-PACE was found in mean CD34+ cells/µL on day 2 of collection and in mean ratio of CD34+ cells/µL on day 2 to day 1.

Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus.

Study Objectives: The effects of intermittent hypoxia (IH) on pancreatic function in the presence of diabetes and the underlying mechanisms are unclear. We hypothesized that IH would exacerbate pancreatic β-cell dysfunction and alter the fatty acids in the male Tallyho/JngJ (TH) mouse, a rodent model of type 2 diabetes.

Design: TH mice were exposed for 14 d to either 8 h of IH or intermittent air (IA), followed by an intraperitoneal glucose tolerance test (IPGTT) and tissue harvest.