Follicular lymphoma patients with KIR2DL2 and KIR3DL1 and their ligands (HLA-C1 and HLA-Bw4) show improved outcome when receiving rituximab.

Background: The ECOG-ACRIN Cancer Research Group evaluated rituximab treatment schedules for patients with newly-diagnosed low-tumor-burden follicular-lymphoma (FL). All patients received 4-weekly rituximab treatments as induction therapy. Clinically-responding patients were randomized to receive rituximab every 13 weeks ("maintenance") vs.

MEF2C Phosphorylation Is Required for Chemotherapy Resistance in Acute Myeloid Leukemia.

In acute myeloid leukemia (AML), chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that knock-in mutant mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MEF2C phosphorylation was required for leukemia stem cell maintenance and induced by MARK kinases in cells.

A Case of Mysterious Impacted Duodenal Foreign Body Presenting with Halitosis.

The majority of gastrointestinal (GI) foreign bodies (FBs) discovered in adults are the result of intentional ingestion, most of which are found in patients with a preexisting psychiatric illness, with substance abuse disorders, or in people seeking secondary gain. No similar case of internal injuries following unintentional ingestion of a barbecue grill cleaning brush bristle has been reported. A 58-year-old Caucasian male with no significant history presented with complaint of halitosis, not improving after oral care and dental hygiene measures.

Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia.

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.

Deregulation of DUX4 and ERG in acute lymphoblastic leukemia.

Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL). Here we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion.

Dynamic left ventricular changes in patients with gestational diabetes: A speckle tracking echocardiography study.

Purpose: The left ventricle (LV) undergoes physiologic remodeling in adaptation to the hemodynamic changes that occur in pregnancy. Speckle tracking echocardiography (STE) is a novel and reliable tool to evaluate subtle myocardial alterations that have been utilized to assess myocardial changes in patients with diabetes mellitus (DM) but not in patients with gestational DM (GDM). We seek to evaluate changes in LV function using STE in patients with GDM compared with women with normal pregnancy.

Minimal Residual Disease in AML: Why Has It Lagged Behind Pediatric ALL?

Although the concept of minimal residual disease (MRD) as an indicator for the quality of treatment response is the same in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), the practice of measuring MRD levels for monitoring response and guiding therapy after induction has been implemented much more rapidly in ALL, particularly pediatric ALL, than in AML. In this perspective we examine the facts and discuss why ALL appears to be more amenable to MRD-shaped risk allocation and a revised definition of complete remission.

Cell signaling-based classifier predicts response to induction therapy in elderly patients with acute myeloid leukemia.

Single-cell network profiling (SCNP) data generated from multi-parametric flow cytometry analysis of bone marrow (BM) and peripheral blood (PB) samples collected from patients >55 years old with non-M3 AML were used to train and validate a diagnostic classifier (DXSCNP) for predicting response to standard induction chemotherapy (complete response [CR] or CR with incomplete hematologic recovery [CRi] versus resistant disease [RD]). SCNP-evaluable patients from four SWOG AML trials were randomized between Training (N = 74 patients with CR, CRi or RD; BM set = 43; PB set = 57) and Validation Analysis Sets (N = 71; BM set = 42, PB set = 53). Cell survival, differentiation, and apoptosis pathway signaling were used as potential inputs for DXSCNP.

Mutated Ptpn11 alters leukemic stem cell frequency and reduces the sensitivity of acute myeloid leukemia cells to Mcl1 inhibition.

PTPN11 encodes the Shp2 non-receptor protein-tyrosine phosphatase implicated in several signaling pathways. Activating mutations in Shp2 are commonly associated with juvenile myelomonocytic leukemia but are not as well defined in other neoplasms. Here we report that Shp2 mutations occur in human acute myeloid leukemia (AML) at a rate of 6.

PRMT4 blocks myeloid differentiation by assembling a methyl-RUNX1-dependent repressor complex.

Defining the role of epigenetic regulators in hematopoiesis has become critically important, because recurrent mutations or aberrant expression of these genes has been identified in both myeloid and lymphoid hematological malignancies. We found that PRMT4, a type I arginine methyltransferase whose function in normal and malignant hematopoiesis is unknown, is overexpressed in acute myelogenous leukemia patient samples. Overexpression of PRMT4 blocks the myeloid differentiation of human stem/progenitor cells (HSPCs), whereas its knockdown is sufficient to induce myeloid differentiation of HSPCs.

Recanalization of failed autogenous conduit utilizing laser revascularization.

The traditional approach for the treatment of restenosis of autogenous vein bypass has been revision of bypass with vein patch angioplasty, interposition jump graft, or thrombectomy procedures for those patients with extensive occlusive disease and limb-threatening ischemia. Endovascular intervention traditionally involves angioplasty of the graft; however, vessels with diffuse disease or extensive longitudinal lesions are generally difficult to revascularize utilizing this technique. Surgical revision of a threatened autogenous vein graft may carry a morbidity rate as high as 13.

Serum lutein response is greater from free lutein than from esterified lutein during 4 weeks of supplementation in healthy adults.

Background: Current data suggest great variability in serum response following lutein ingestion from various sources.

Objective: To compare the relative serum response during supplementation with free lutein (fL) and lutein esters (Le).

Methods: 72 volunteers (23-52 years; body mass index [BMI] >20 and <30 kg/m2; baseline serum lutein <20 µg/dL [<352 nmol/L]) were identified.

Chronic kidney disease staging in nursing home and community older adults: does the choice of cockcroft-gault, modification of diet in renal disease study, or the chronic kidney disease epidemiology collaboration initiative equations matter?

Objective: To compare the chronic kidney disease (CKD) stages derived from GFR estimates using 3 different formulae in a sample of older adults from the community and long term care settings.

Participants: Data from 1535 older, hospitalized patients (2000-2008) were collected; individuals were hospitalized for acute illness unrelated to renal function.

Measurements: Patient demographics, pertinent medical history, and routine laboratory test results were collected.

Surrogate marker profiles for genetic lesions in acute leukemias.

The basic hypothesis of surrogate marker profiles is that individual genetic lesions result in characteristic distortions of the cellular phenotype with some predictable consistency that can be exploited by sophisticated immunophenotyping. While cytogenetic and molecular aberrancies currently are accepted prognostic predictors in acute leukemias, single antigen expression and even antigenic profiles rarely impact on prognosis. However, increasingly, phenotypes are delineated which can serve as surrogates for underlying genetic aberrations of clinical importance.

Recurrent cerebral embolism associated with indwelling catheter in the presence of anomalous neck venous structures.

Persistent left superior vena cava (PLSVC) is the most common central venous anomaly in the thorax, which may remain asymptomatic throughout life. Indwelling catheters that are increasingly used in oncology practice may result in complications in the presence of PLSVC. The authors report an unusual case of recurrent ischemic attacks each time a portacath was accessed in a patient with breast cancer and PLSVC.

Experience with sorafenib and the elderly patient.

Renal cell carcinoma primarily affects older individuals. Approximately half of all new renal cell carcinoma diagnoses are made in persons 65 years of age or older. Devising a treatment plan for the elderly patient population requires special consideration.

Abdominal aortitis after use of granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (G-CSF) is a recombinant human glycoprotein that promotes proliferation and differentiation of granulocytic-committed progenitors. It is commonly used to treat neutropenia and is generally well tolerated. Occurrences of rare but serious adverse events in association with the use of G-CSF have been described.

Erythropoiesis-stimulating agents in anemia: use and misuse.

Erythropoiesis-stimulating agents (ESAs) have been in use for 2 decades. After the initial introduction for their use in anemia of end-stage renal disease, indications for the use of ESAs have widened to anemia of predialysis chronic kidney disease, cancer chemotherapy, HIV disease and orthopedic surgery. Along with the considerable benefits associated with the use of ESAs, adverse events have become apparent, in large part from overcorrection of the anemia.

Radiation therapy compared with chemotherapy for consolidation of chemotherapy-induced remission of advanced Hodgkin lymphoma: a study by the Eastern Co-operative Oncology Group (E1476) with >20 years follow-up.

MOPP-Bleo (nitrogen mustard, vincristine, procarbazine, prednisone and bleomycin) induction therapy was given to 253 evaluable patients with Hodgkin lymphoma, stages IIIB, III(s), or IV. Complete response (CR) occurred in 145 patients (57%) and partial response (PR) in 93 (37%). Of those 238 responders, 178 were randomized to consolidation therapy, and 164 were eligible and analyzable, including 114 CRs [55 patients randomized to ABVD and 59 to radiation therapy (RT)] and 50 partial responders (PRs) (25 each randomized to ABVD and RT).

A retrospective review of glargine use in pregnancy.

Objective: To review the obstetric outcome of 240 diabetic pregnancies maintained on basal glargine insulin.

Study Design: This is a retrospective review of the medical data from 240 pregnant diabetics who received glargine as a basal insulin. Perinatal outcome was abstracted from August 29, 2001, to December 31, 2007.

Effect of temsirolimus versus interferon-alpha on outcome of patients with advanced renal cell carcinoma of different tumor histologies.

Purpose Exploratory subgroup analyses from the phase 3 global advanced renal cell carcinoma (ARCC) trial were conducted to assess the influence of tumor histology on outcome of patients treated with temsirolimus (Torisel) or interferon-alpha (IFN). Patients and methods Patients with ARCC including clear cell and other types such as papillary and chromophobe histologies received either IFN (3 million units [MU] subcutaneously three times weekly, escalating to 18 MU) or temsirolimus (25 mg intravenously weekly). Results Approximately 80% of patients had clear cell and 20% of patients had other histologies, the majority of which were papillary.

Treatment of hematologic neoplasms with new immunomodulatory drugs (IMiDs).

Thalidomide and its derivatives represent a new class of antineoplastic drugs (IMiDs), which has been especially effective in certain hematologic malignancies. These agents have anti-inflammatory, antiangiogenic, and immunomodulatory properties, and target tumor cells by direct cytotoxicity and indirectly by interfering with several components of the bone marrow microenvironment. Thalidomide analogs that retain antitumor activity equal to or greater than the parent compound, but with less toxicity, have been developed.