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.

Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia.

T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a dismal overall prognosis, including a relapse rate of up to 25%, mainly because of the lack of non-cytotoxic targeted therapy options. Drugs that target the function of key epigenetic factors have been approved in the context of haematopoietic disorders, and mutations that affect chromatin modulators in a variety of leukaemias have recently been identified; however, 'epigenetic' drugs are not currently used for T-ALL treatment. Recently, we described that the polycomb repressive complex 2 (PRC2) has a tumour-suppressor role in T-ALL.

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.

Prevention of venous thromboembolism: practice patterns in 17 geographically diverse long term care facilities in the United States: part 1 of 2 (an AMDA Foundation project).

Introduction: Current guidelines recommend antithrombotic prophylaxis for venous thromboembolism (VTE) using risk assessment, factoring contraindications. This report represents a summary of current practice patterns to prevent VTE in long term care as Phase 1 of a 3-phase educational intervention study. PHASE 1

Participants: Participants were 376 new admissions/readmissions (77 ± 12 [SD] years; 67% female) from 17 geographically diverse long term care facilities (3260 total beds).

Prevention of venous thromboembolism in long term care: results of a multicenter educational intervention using clinical practice guidelines: part 2 of 2 (an AMDA Foundation project).

Introduction: Implementation of prophylaxis for venous thomboembolism (VTE) through risk assessment based on clinical practice guidelines (CPGs) is variably adopted in long term care facilities (LTCF). Current guidelines recommend venous thromboembolism prophylaxis (VTE-P) following risk assessment, individualized to patient status. In LTCF, differing comorbidity, life-expectancy, ethical, and quality-of-life issues may warrant a unique approach.

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.

Warfarin: implementing its safe use in hospitalized patients from nursing homes and community through a performance improvement initiative.

Introduction: Warfarin is increasingly used to prevent thromboembolism but adverse drug events (ADEs) are common. The National Safety Goals (3E) 2008 recommend that institutions develop processes to monitor the safe use of warfarin. Despite these guidelines, adverse events (bleeding) are common.

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.

Novel management of pruritus in patients treated with IL-2 for metastatic renal cell carcinoma and malignant melanoma.

Pruritus has been a side effect, associated with several biologic response modifiers, most commonly interferons and interleukins. Reports of pruritus are anecdotal and have not been a focus of attention. Itch fibers are essentially pain fibers, and gabapentin is used for neuropathic pain.

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.