Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis.

While emerging data suggest nucleotide oligomerization domain receptor 1 (NOD1), a cytoplasmic pattern recognition receptor, may play an important and complementary role in the immune response to bacterial infection, its role in cancer metastasis is entirely unknown. Hence, we sought to determine the effects of NOD1 on metastasis. NOD1 expression in paired human primary colon cancer, human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting (WB). Clinical significance of NOD1 was assessed using TCGA survival data. A series of in vitro and in vivo functional assays, including adhesion, migration, and metastasis, was conducted to assess the effect of NOD1. C12-iE-DAP, a highly selective NOD1 ligand derived from gram-negative bacteria, was used to activate NOD1. ML130, a specific NOD1 inhibitor, was used to block C12-iE-DAP stimulation. Stable knockdown (KD) of NOD1 in human colon cancer cells (HT29) was constructed with shRNA lentiviral transduction and the functional assays were thus repeated. Lastly, the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase inhibitors. Our data demonstrate that NOD1 is highly expressed in human colorectal cancer (CRC) and human and murine CRC cell lines. Clinically, we demonstrate that this increased NOD1 expression negatively impacts survival in patients with CRC. Subsequently, we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion, migration and metastasis. These effects are predominantly mediated via the p38 mitogen activated protein kinase (MAPK) pathway. This is the first study implicating NOD1 in cancer metastasis, and thus identifying this receptor as a putative therapeutic target.

Subcutaneous Immunoglobulin Therapy for Chronic Inflammatory Demyelinating Polyneuropathy: A Nursing Perspective.

Chronic inflammatory demyelinating polyneuropathy (CIDP), an immune-mediated peripheral neuropathy, is frequently treated with long-term maintenance intravenous immunoglobulin (IVIG). However, disadvantages of IVIG are the systemic adverse reactions, lengthy infusions, and need for vascular access. Subcutaneous immunoglobulin (SCIG) addresses many of the issues encountered by those unable, or unwilling, to tolerate the treatment burden of long-term IVIG. Subcutaneous immunoglobulin, a 20% solution stabilized with L-proline, is US Food and Drug Administration-approved for CIDP maintenance therapy in patients after being stabilized with IVIG. Approval was based on a randomized, double-blind, placebo-controlled trial where SCIG demonstrated superiority over placebo and was safe and efficacious in maintaining function. In addition to reviewing the primary efficacy results from the clinical trial, this article aims to update the neurology nursing community on a new option for long-term management of CIDP, including the practicalities of initiating and maintaining patients on SCIG therapy.

Training patients for self-administration of a new subcutaneous C1-inhibitor concentrate for hereditary angioedema.

AIMS: The aim of this study was to provide recommendations for training patients with hereditary angioedema, based on nursing clinical trial experience, to self-administer subcutaneous C1-INH (C1-INH[SC]) used as routine prophylaxis. BACKGROUND: A volume-reduced, subcutaneous C1-INH concentrate (C1-INH(SC); HAEGARDA®; CSL Behring) was recently FDA-approved for the routine prevention of hereditary angioedema attacks. Nurses will play an important role in patient training. DESIGN: Review of a phase 3, randomized, placebo-controlled, double-blind, crossover trial of C1-INH(SC) (COMPACT) and summary of recommendations for training patients based on nurses' "hands-on experience." METHODS: A panel of nurses with clinical trial experience provided recommendations for patient training. RESULTS: Practical suggestions and guidelines were compiled regarding patient selection, product reconstitution and administration and patient follow-up. Successful patient self-administration of C1-INH(SC) can be greatly facilitated by qualified nursing intervention. The information provided in this paper will be useful to nurses anywhere who have an opportunity to interact with patients dealing with hereditary angioedema.

Decreasing SMPD1 activity in BEAS-2B bronchial airway epithelial cells results in increased NRF2 activity, cytokine synthesis and neutrophil recruitment.

Niemann-Pick disease (NPD) type B is a rare autosomal recessive disease characterized by variable levels of impairment in sphingomyelin phosphodiesterase 1 (SMPD1) activity. Lung involvement is the most important prognostic factor in NPD-B, with recurrent respiratory infections starting in infancy being the major cause of morbidity and mortality. We hypothesized that decreased SMPD1 activity impaired airway epithelium host defense response. SMPD1 activity was reduced using inducible shRNA. Surprisingly, decreasing SMPD1 activity by 50%, resulted in increased neutrophil recruitment, both at baseline and in response to bacterial stimulation. This correlated with elevated levels of cytokine mRNA shown to contribute to neutrophil recruitment in unstimulated (e.g. IL-8 and GRO-α) and infected cells (e.g. IL-8, GRO-α, GM-CSF and CCL20). Instead of preventing the host defence responses, decreased SMPD1 activity results in an inflammatory response even in the absence of infection. Moreover, decreasing SMPD1 activity resulted in a pro-oxidative shift. Accordingly, expression of an inactive mutant, SMPD1[L225P] but not the WT enzyme increased activation of the antioxidant transcription factor NRF2. Therefore, decreasing SMPD1 activity by 50% in airway epithelial cells, the equivalent of the loss of one allele, results in the accumulation of oxidants that activates NRF2 and a concomitant increased cytokine production as well as neutrophil recruitment. This can result in a chronic inflammatory state that impairs host defence similar to scenarios observe in other chronic inflammatory lung disease such as Chronic Obstructive Pulmonary Disease or Cystic Fibrosis.

Subcutaneous immunoglobulin replacement therapy: ensuring success.

Subcutaneous immunoglobulin (SCIg) infusions are an option for patients requiring immunoglobulin therapy. Nurses are uniquely positioned to advocate for patients and to teach them how to successfully manage their infusions. The purpose of this review is to describe SCIg therapy and to provide teaching instructions as well as creative tips to ensure treatment success.

Participant survey results from the Starting Hizentra Administration with Resources and Education (SHARE) program.

Increased use of specialized infusion therapies has necessitated training of health care providers and patients. The Starting Hizentra Administration with Resources and Education (SHARE) program provided 709 US participants with information to educate patients with primary immunodeficiency disease (PIDD) on self-administration of 20% subcutaneous immunoglobulin (SCIG). Postprogram surveys assessed participants' experience and opinion of 20% SCIG. The most frequent questions about 20% SCIG regarded subcutaneous challenges (29%). Participants stated that all attributes of SCIG were beneficial (51%), and they expressed interest in future programs on non-PIDD diseases (26%). Survey results will assist in future SHARE and other relevant educational program optimization.

Importance of ancillary supplies for subcutaneous immunoglobulin infusion: management of the local infusion site.

A number of ancillary supplies are used in the process of administering subcutaneous immunoglobulin. The particular type of ancillary supplies used (needles, tubing, and tape) may contribute to the development of issues at the local infusion site. Patient case studies demonstrate that changes in the choice of ancillary supplies can often alleviate these issues. The use of alternative ancillary supplies should be considered prior to the possibility of changing immunoglobulin replacement products in patients experiencing local infusion-site issues in order to improve outcomes and increase compliance. A treatment progression algorithm of ancillary supply adjustments has been developed.

Nursing guidelines for administration of immunoglobulin replacement therapy.

Immunoglobulin (Ig) replacement therapy, given as regular infusions of pooled human Ig, is the recognized treatment of humoral immunodeficiencies characterized by hypogammaglobulinemia and impaired antibody responses. It is a safe, effective therapy when delivered by nurses who have been educated to oversee and/or provide these infusions. Guidelines for administration have been developed by the Immune Deficiency Foundation Nurse Advisory Committee to provide a framework and guidance to those nurses administering this therapy.

Improved quality of life, immunoglobulin G levels, and infection rates in patients with primary immunodeficiency diseases during self-treatment with subcutaneous immunoglobulin G.

OBJECTIVES: Primary immunodeficiency diseases (PIDDs) include a large class of genetically heterogeneous disorders which predispose patients to significant risk of serious and chronic/recurrent infections, as well as reduced quality of life (QoL). Intravenous immunoglobulin (IVIG) therapy improves the well being of PIDD patients; however, the need for venous access and potentially severe side effects frequently require administration in medical facilities. We evaluated the long-term (12-month) experience with home-based self infusions of subcutaneous immune globulin (SCIG) in patients with PIDD on health-related QoL, rates of serious bacterial infections, and all other infections. METHODS: Adults (n = 42) and children (n = 9) with PIDD, previously treated with clinic-based IVIG, were trained to self administer SCIG at home. QoL (SF-36(R) and CHQ-PF50 questionnaires), serious bacterial infections, serum immunoglobulin G (IgG) levels, overall infections, and incidence of adverse events were recorded at predetermined intervals. RESULTS: All patients had improved perceptions of general health (adults P = 0.047, children P = 0.037). Adults also had marked improvement in the bodily pain and vitality assessments, and parents had improved perceptions of personal and family activities. Serum IgG levels were maintained at mean levels 25% higher than previous troughs on IVIG. There were 162 infections overall for an annual rate of 3.42/patient, but only 1 serious bacterial infection was observed (0.03/patient/yr). An average of 4.5 days/yr was missed from work or school per patient. CONCLUSIONS: Home SCIG therapy was safe and led to improved perceptions of general health, higher serum IgG levels, and very low rates of infections and days missed from work/school.

Primary immunodeficiency disease: a model for case management of chronic diseases.

PURPOSE/OBJECTIVES: Patient-centered chronic care management is a new model for the management of rare chronic diseases such as primary immunodeficiency disease (PIDD). This approach emphasizes helping patients become experts on the management of their disease as informed, involved, and interactive partners in healthcare decisions with providers. Because only a few patients are affected by rare illnesses, these patients are forced to become knowledgeable about their disease and therapies and to seek treatment from a healthcare team, which includes physicians and nurse specialists who are equipped to manage the complexity of the disease and its comorbidities. Importantly, therapy for PIDD can be self-administered at home, which has encouraged the transition toward a proactive stance that is at the heart of patient-centered chronic care management. We discuss the evolution of therapy, the issues with the disease, and challenges with its management within the framework of other chronic disease management programs. Suggestions and rationale to move case management of PIDD forward are presented with the intent that sharing our experiences will improve process and better manage outcomes in this patient population. PRIMARY PRACTICE SETTINGS: The patient-centered model for the management of PIDD is applicable to the primary care settings, where nurse case managers assist patients through education, support them and their families, and facilitate access to community resources in an approach, which has been described as "guided care." The model also applies specifically to immunology centers where patients receive treatment or instruction on its self-administration at home. FINDINGS/CONCLUSIONS: Patient-centered management of PIDD, with its emphasis on full involvement of patients in their treatment, has the potential to improve compliance with treatment, and thus patient outcomes, as well as patients' quality of life. IMPLICATIONS FOR CASE MANAGEMENT: The patient-centered model expands the traditional model of chronic disease management, which relies on evidence-based medicine, provider expertise, clinical information systems, and patient education. This approach supports patient self-management with strategies that empower and prepare them for their role as expert patients.

Developing practice guidelines for the administration of intravenous immunoglobulin.

As the use of intravenous immunoglobulin (IGIV) continues to expand, infusion nurses have a greater need for a comprehensive understanding of the product, patient risk factors, and comorbidities when developing guidelines for administering IGIV. Because immunoglobulin therapy is a blood derivative product, many nurses may not have as much experience administering this type of infusion. This article provides an in-depth overview of immunoglobulin therapy and helps to define the infusion nurse's major role in coordinating, assessing, and ensuring patient safety during IGIV administration.