Assessment and Management of Delirium in Critically Ill Veterans.

Background: Delirium is a complex syndrome prevalent in the intensive care unit. It has been associated with significant morbidity including distress, longer hospital stays, prolonged cognitive impairment, and increased mortality.

Objective: To describe a nurse-led interdisciplinary quality improvement initiative to increase nurses' knowledge of delirium, documentation of delirium assessment, and patient mobility.

Role of the Wound, Ostomy and Continence Nurse in Continence Care: 2018 Update.

The Wound, Ostomy and Continence Nurses Society believes the tri-specialty certified nurse (Certified Wound Ostomy Continence Nurse [CWOCN]) or advanced practice tri-specialty certified nurse (Certified Wound Ostomy Continence Nurse-Advanced Practice [CWOCN-AP]) possesses unique knowledge, expertise for assessment, and first-line management of incontinence as well as for prevention of incontinence. The CWOCN or CWOCN-AP provides care and consultation in the treatment of potential and actual skin complications through absorption, and containment, in persons with urinary, fecal, or dual incontinence. This executive summary describes the role of the CWOCN or CWOCN-AP in the delivery of continence care across care settings.

Hyper IgM Syndrome: a Report from the USIDNET Registry.

Purpose: The United States Immunodeficiency Network (USIDNET) patient registry was used to characterize the presentation, genetics, phenotypes, and treatment of patients with Hyper IgM Syndrome (HIGM).

Methods: The USIDNET Registry was queried for HIGM patient data collected from October 1992 to July 2015. Data fields included demographics, criteria for diagnosis, pedigree analysis, mutations, clinical features, treatment and transplant records, laboratory findings, and mortality.

Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015.

We report the updated classification of primary immunodeficiencies compiled by the Primary Immunodeficiency Expert Committee (PID EC) of the International Union of Immunological Societies (IUIS). In the two years since the previous version, 34 new gene defects are reported in this updated version. For each disorder, the key clinical and laboratory features are provided.

CD19 controls Toll-like receptor 9 responses in human B cells.

Background: CD19 is a B cell-specific molecule that serves as a major costimulatory molecule for amplifying B-cell receptor (BCR) responses. Biallelic CD19 gene mutations cause common variable immunodeficiency in human subjects. BCR- and Toll-like receptor (TLR) 9-induced B-cell responses are impaired in most patients with common variable immunodeficiency.

The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies.

There are now nearly 300 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. For each of these five categories, a growing variety of phenotypes are ascribed to Primary Immunodeficiency Diseases (PID), making PIDs a rapidly expanding field of medicine. The International Union of Immunological Societies (IUIS) PID expert committee (EC) has published every other year a classification of these disorders into tables, defined by shared pathogenesis and/or clinical consequences.

Enteroviral Infection in a Patient with BLNK Adaptor Protein Deficiency.

B-cell linker (BLNK) protein is a non-redundant adaptor molecule in the signaling pathway activated by (pre) B-cell antigen receptor signals. We present two siblings with a homozygous deleterious frameshift mutation in BLNK, resulting in a block of B cell development in the bone marrow at the preB1 to preB2 stage, absence of circulating B cells and agammaglobulinemia. This is the first description of an enteroviral infection associated arthritis and dermatitis in a patient with BLNK deficiency.

Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies.

Can genetic and clinical findings made in a single patient be considered sufficient to establish a causal relationship between genotype and phenotype? We report that up to 49 of the 232 monogenic etiologies (21%) of human primary immunodeficiencies (PIDs) were initially reported in single patients. The ability to incriminate single-gene inborn errors in immunodeficient patients results from the relative ease in validating the disease-causing role of the genotype by in-depth mechanistic studies demonstrating the structural and functional consequences of the mutations using blood samples. The candidate genotype can be causally connected to a clinical phenotype using cellular (leukocytes) or molecular (plasma) substrates.

Discovery of single-gene inborn errors of immunity by next generation sequencing.

Many patients with clinical and laboratory evidence of primary immunodeficiency do not have a gene specific diagnosis. The use of next generation sequencing, particularly whole exome sequencing, has given us an extraordinarily powerful tool to identify the disease-causing genes in some of these patients. At least 34 new gene defects have been identified in the last 4 years.

Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency.

We report the updated classification of primary immunodeficiencies (PIDs) compiled by the Expert Committee of the International Union of Immunological Societies. In comparison to the previous version, more than 30 new gene defects are reported in this updated version. In addition, we have added a table of acquired defects that are phenocopies of PIDs.

Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts.

The present uncertainty of which live viral or bacterial vaccines can be given to immunodeficient patients and the growing neglect of societal adherence to routine immunizations has prompted the Medical Advisory Committee of the Immune Deficiency Foundation to issue recommendations based on published literature and the collective experience of the committee members. These recommendations address the concern for immunodeficient patients acquiring infections from healthy subjects who have not been immunized or who are shedding live vaccine-derived viral or bacterial organisms. Such transmission of infectious agents can occur within the hospital, clinic, or home or at any public gathering.

A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells.

Approximately 90% of patients with isolated agammaglobulinemia and failure of B cell development have mutations in genes required for signaling through the pre–B cell and B cell receptors. The nature of the gene defect in the majority of remaining patients is unknown. We recently identified 4 patients with agammaglobulinemia and markedly decreased numbers of peripheral B cells.

A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside.

The number of genetically defined Primary Immunodeficiency Diseases (PID) has increased exponentially, especially in the past decade. The biennial classification published by the IUIS PID expert committee is therefore quickly expanding, providing valuable information regarding the disease-causing genotypes, the immunological anomalies, and the associated clinical features of PIDs. These are grouped in eight, somewhat overlapping, categories of immune dysfunction.

Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia.

Isolated congenital asplenia (ICA) is characterized by the absence of a spleen at birth in individuals with no other developmental defects. The patients are prone to life-threatening bacterial infections. The unbiased analysis of exomes revealed heterozygous mutations in RPSA in 18 patients from eight kindreds, corresponding to more than half the patients and over one-third of the kindreds studied.

Primary immunodeficiencies: a rapidly evolving story.

The characterization of primary immunodeficiencies (PIDs) in human subjects is crucial for a better understanding of the biology of the immune response. New achievements in this field have been possible in light of collaborative studies; attention paid to new phenotypes, infectious and otherwise; improved immunologic techniques; and use of exome sequencing technology. The International Union of Immunological Societies Expert Committee on PIDs recently reported on the updated classification of PIDs.

Anorectal atresia and variants at predicted regulatory sites in candidate genes.

Anorectal atresia is a serious birth defect of largely unknown etiology but candidate genes have been identified in animal studies and human syndromes. Because alterations in the activity of these genes might lead to anorectal atresia, we selected 71 common variants predicted to be in transcription factor binding sites, CpG windows, splice sites, and miRNA target sites of 25 candidate genes, and tested for their association with anorectal atresia. The study population comprised 150 anorectal atresia cases and 623 control infants without major malformations.

Evaluation of common genetic variants in 82 candidate genes as risk factors for neural tube defects.

Background: Neural tube defects (NTDs) are common birth defects (~1 in 1000 pregnancies in the US and Europe) that have complex origins, including environmental and genetic factors. A low level of maternal folate is one well-established risk factor, with maternal periconceptional folic acid supplementation reducing the occurrence of NTD pregnancies by 50-70%. Gene variants in the folate metabolic pathway (e.

Successful approach to treatment of Helicobacter bilis infection in X-linked agammaglobulinemia.

Helicobacter bilis, an unusual cause of chronic infections in patients with X-linked agammaglobulinemia (XLA), is notoriously difficult to diagnose and eradicate. Based on the limited number of cases reported worldwide, we highlight the typical features of H. bilis infection in XLA and provide a rational and successful approach to diagnosis and treatment of this challenging infection.

A prospective cohort study of the prevalence of growth, facial, and central nervous system abnormalities in children with heavy prenatal alcohol exposure.

Background: Most children who are exposed to large quantities of alcohol in utero do not develop fetal alcohol syndrome (FAS). Population-based prospective data on the risk of developing components of fetal alcohol spectrum disorders (FASD), however, are limited.

Methods: This was a prospective cohort study of 9,628 women screened during their first prenatal appointment in Chile, which identified 101 who consumed at least 4 drinks/d (exposed) matched with 101 women with no reported alcohol consumption during pregnancy (unexposed).

Hirschsprung's disease and variants in genes that regulate enteric neural crest cell proliferation, migration and differentiation.

Hirschsprung's disease (HSCR) results from failed colonization of the embryonic gut by enteric neural crest cells (ENCCs); colonization requires RET proto-oncogene (RET) signaling. We sequenced RET to identify coding and splice-site variants in a population-based case group and we tested for associations between HSCR and common variants in RET and candidate genes (ASCL1, homeobox B5 (HOXB5), L1 cell adhesion molecule (L1CAM), paired-like homeobox 2b (PHOX2B), PROK1 and PROKR1) chosen because they are involved in ENCC proliferation, migration and differentiation in animal models. We conducted a nested case-control study of 304 HSCR cases and 1215 controls.