Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study.

Background: About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn.

Methods: For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data were available.

Clonal evolution in chronic lymphocytic leukemia: impact of subclonality on disease progression.

In recent years, next-generation sequencing has unraveled the molecular landscape in chronic lymphocytic leukemia with the discovery of a number of recurrently mutated genes. Mutations in several of these genes, such as NOTCH1, SF3B1 and BIRC3, are linked to a more aggressive disease with early disease progression, short time-to-first-treatment and even chemorefractoriness. Although in its infancy, we have also begun to understand the complex dynamics of subclonal diversity and its impact on disease outcome.

Palliative care, Version 1.2014. Featured updates to the NCCN Guidelines.

The NCCN Guidelines for Palliative Care provide interdisciplinary recommendations on palliative care for patients with cancer. These NCCN Guidelines Insights summarize the NCCN panel's discussions and guideline updates from 2013 and 2014. These include modifications/additions to palliative care screening and assessment protocols, new considerations for discussing the benefits and risks of anticancer therapy, and approaches to advance care planning.

Targeting metallo-carbapenemases via modulation of electronic properties of cephalosporins.

The global proliferation of metallo-carbapenemase-producing Enterobacteriaceae has created an unmet need for inhibitors of these enzymes. The rational design of metallo-carbapenemase inhibitors requires detailed knowledge of their catalytic mechanisms. Nine cephalosporins, structurally identical except for the systematic substitution of electron-donating and withdrawing groups in the para position of the styrylbenzene ring, were synthesized and utilized to probe the catalytic mechanism of New Delhi metallo-β-lactamase (NDM-1).

Fetal myelomeningocele closure: technical considerations.

Myelomeningocele (MMC) is one of the most common serious congenital malformations. Typically this condition has been treated with closure of the MMC defect shortly after birth. In general, surgery for MMC aims to provide a multilayered closure to provide protection to the neural elements, prevent leakage of spinal fluid and reduce infection risks.

Fetal myelomeningocele repair: the post-MOMS experience at the Children's Hospital of Philadelphia.

Background: Fetal myelomeningocele (fMMC) repair has become accepted as a standard of care option in selected circumstances. We reviewed our outcomes for fMMC repair from referral and evaluation through surgery, delivery and neonatal discharge.

Material And Methods: All patients referred for potential fMMC repair were reviewed from January 1, 2011 through March 7, 2014.

COI haplotype groups in Mesocriconema (Nematoda: Criconematidae) and their morphospecies associations.

Without applying an a priori bias for species boundaries, specimen identities in the plant-parasitic nematode genus Mesocriconema were evaluated by examining mitochondrial COI nucleotide sequences, morphology, and biogeography. A total of 242 specimens that morphologically conformed to the genus were individually photographed, measured, and amplified by a PCR primer set to preserve the linkage between specimen morphology and a specific DNA barcode sequence. Specimens were extracted from soil samples representing 45 locations across 23 ecoregions in North America.

Immunogenetic studies of chronic lymphocytic leukemia: revelations and speculations about ontogeny and clinical evolution.

Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IG) has proved instrumental in dissecting chronic lymphocytic leukemia (CLL) pathogenesis. Initially, it was the finding that the level of somatic hypermutations in rearranged IG heavy-chain genes could define two CLL subtypes associated with a different clinical course that drew attention. As the years ensued, this not only continued to hold strong, but also revealed an unprecedented BcR restriction (aptly coined as "stereotypy"), thus cementing the idea that antigenic elements select the leukemic clones.

A practice change initiative to improve the provision of enteral nutrition to intensive care patients.

Aim: To describe a practice change initiative that improved the provision of enteral nutrition (EN) to patients in a New Zealand tertiary intensive care unit (ICU).

Methods: The project reviewed and summarized EN literature, amended local policy, and an evidence-based EN delivery algorithm was developed. The EN practice change initiative was implemented and evaluated.

Pharmacogenetics of warfarin in a paediatric population: time in therapeutic range, initial and stable dosing and adverse effects.

Warfarin is used in paediatric populations, but dosing algorithms incorporating pharmacogenetic data have not been developed for children. Previous studies have produced estimates of the effect of polymorphisms in Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) on stable warfarin dosing, but data on time in therapeutic range, initial dosing and adverse effects are limited. Participants (n=97) were recruited, and routine clinical data and salivary DNA samples were collected from all participants and analysed for CYP2C9*2, *3 and VKORC1-1639 polymorphisms.

Lymphocytic esophagitis in children.

Background: Lymphocytic esophagitis (LE) is a term recently suggested for the finding of >20 intraepithelial lymphocytes/high-power field in an esophageal biopsy with no more than a rare granulocyte. Two prior studies of LE suggested an association of LE with Crohn's disease (CD) in young patients, but there has been no systematic review of a large pediatric cohort to determine the prevalence and clinical associations of LE in children.

Methods: All esophageal biopsies performed at a tertiary care pediatric medical center in 2005 were identified (580 biopsies from 545 unique patients).

Recurrent mutations refine prognosis in chronic lymphocytic leukemia.

Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.

Access to primary care physicians differs by health insurance coverage in Mississippi.

Objectives: The objective of the study was to measure how access to primary health care in Mississippi varies by type of health insurance.

Methods: We called primary care physician (general practitioner, family practice, internal medicine, obstetrics/gynecology, and pediatric) offices in Mississippi three times, citing different types of health insurance coverage in each call, and asked for a new patient appointment with a physician.

Results: Of all of the offices contacted, 7% of offices were not currently accepting new patients who had private insurance, 15% of offices were not currently accepting new Medicare patients, 38% were not currently accepting new Medicaid patients, and 9% to 21% of office calls were unresolved in one telephone call to the office.

Acquired initiating mutations in early hematopoietic cells of CLL patients.

Unlabelled: Appropriate cancer care requires a thorough understanding of the natural history of the disease, including the cell of origin, the pattern of clonal evolution, and the functional consequences of the mutations. Using deep sequencing of flow-sorted cell populations from patients with chronic lymphocytic leukemia (CLL), we established the presence of acquired mutations in multipotent hematopoietic progenitors. Mutations affected known lymphoid oncogenes, including BRAF, NOTCH1, and SF3B1.

Long-term follow-up and second malignancies in 487 patients with hairy cell leukaemia.

A large, multicentre, retrospective survey of patients with hairy cell leukaemia (HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long-term effects of the established purine nucleoside analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL.

Identification of binding sites in Huntingtin for the Huntingtin Interacting Proteins HIP14 and HIP14L.

Huntington disease is an adult onset neurodegenerative disease characterized by motor, cognitive, and psychiatric dysfunction, caused by a CAG expansion in the HTT gene. Huntingtin Interacting Protein 14 (HIP14) and Huntingtin Interacting Protein 14-like (HIP14L) are palmitoyl acyltransferases (PATs), enzymes that mediate the post-translational addition of long chain fatty acids to proteins in a process called palmitoylation. HIP14 and HIP14L interact with and palmitoylate HTT and are unique among PATs as they are the only two that have an ankyrin repeat domain, which mediates the interaction between HIP14 and HTT.

A cost-effectiveness analysis of postoperative goal-directed therapy for high-risk surgical patients.

Objectives: Patients undergoing major surgery are at high risk of increased postoperative morbidity and mortality. Goal-directed therapy has been shown to improve outcomes when commenced in the early postoperative period, yet the economic impact remains unclear. The aim of our study was to assess the cost effectiveness of goal-directed therapy as part of postoperative management.

Local vibrations and negative thermal expansion in ZrW2O8.

We present an x-ray pair distribution function (XPDF) analysis and extended x-ray absorption fine structure (EXAFS) data for ZrW2O8 (10-500 K) with a focus on the stiffness of the Zr-O-W linkage. The XPDF is highly sensitive to W-Zr and W-W correlations, but much less so to O-O or W-O correlations. The Zr-W peak in the XPDF data has a weak temperature dependence and, hence, this linkage is relatively stiff and does not permit bending of the Zr-O-W link.

Intraoperative neurophysiological monitoring in patients undergoing tethered cord surgery after fetal myelomeningocele repair.

Object: Fetal myelomeningocele closure has been shown to be advantageous in a number of areas. In this study, the authors report on neural function in patients who had previously undergone fetal myelomeningocele repair and returned to the authors' institution for further surgery that included intraoperative neurophysiological monitoring.

Methods: The authors retrospectively reviewed data obtained in 6 cases involving patients who underwent fetal myelomeningocele repair and later returned to their institution for spinal cord untethering.

Lymphoma development in patients with autoimmune and inflammatory disorders--what are the driving forces?

For decades, it has been known that patients with certain autoimmune and inflammatory disorders, such as rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS), have an increased risk of developing malignant lymphoma. Although the clinico-biological reasons for this association remain largely unknown, our knowledge has improved and new insights have been obtained. First, the direct link between autoimmunity and lymphomagenesis has been strengthened by large epidemiological studies showing a consistent risk increase of lymphoma associated with certain autoimmune/inflammatory conditions in independent cohorts from different countries.