Most Premature Surveillance Colonoscopy Is Not Attributable to Bowel Preparation or New Clinical Indications.

BACKGROUND AND AIMS: Surveillance colonoscopy frequently occurs prior to recommended intervals. Studies delineating the reasons why premature surveillance occurs are limited. We sought to define the frequency in which premature surveillance colonoscopy occurs in the setting of an inadequate bowel preparation or with a provided patient clinical indication versus when premature surveillance colonoscopy occurs without any provided discernible rationale in the setting of adequate bowel preparation. METHODS: A retrospective cross-sectional cohort study of 700 patients undergoing colonoscopy for an indication of "surveillance of polyps" from 2008 to 2014 at two tertiary-care referral centers was carried out. Patients were deemed either "adherent" or "premature" based on US Multi-Society Task Force guideline intervals for surveillance colonoscopy. A documented decision-making rationale for premature surveillance was determined through review of the electronic medical record with assessment of clinical notes and endoscopy order and report. RESULTS: Premature surveillance occurred in 43.0 % (n = 301) of all surveillance colonoscopies performed. Among the premature cases, rationale was attributed to inadequate bowel preparation in 17.3 % (n = 52) and due to a new clinical indication in 21.6 % (n = 65). Most commonly, in 61.1 % (n = 184) of premature cases, no rationale was documented for the early colonoscopy. CONCLUSIONS: Documented decision-making rationale for premature surveillance colonoscopy is usually absent in premature cases with inadequate bowel preparation and new clinical indications explaining only a minority of the occurrences.

Human immunodeficiency virus infection alters tumor necrosis factor alpha production via Toll-like receptor-dependent pathways in alveolar macrophages and U1 cells.

Human immunodeficiency virus (HIV)-positive persons are predisposed to pulmonary infections, even after receiving effective highly active antiretroviral therapy. The reasons for this are unclear but may involve changes in innate immune function. HIV type 1 infection of macrophages impairs effector functions, including cytokine production. We observed decreased constitutive tumor necrosis factor alpha (TNF-alpha) concentrations and increased soluble tumor necrosis factor receptor type II (sTNFRII) in bronchoalveolar lavage fluid samples from HIV-positive subjects compared to healthy controls. Moreover, net proinflammatory TNF-alpha activity, as measured by the TNF-alpha/sTNFRII ratio, decreased as HIV-related disease progressed, as manifested by decreasing CD4 cell count and increasing HIV RNA (viral load). Since TNF-alpha is an important component of the innate immune system and is produced upon activation of Toll-like receptor (TLR) pathways, we hypothesized that the mechanism associated with deficient TNF-alpha production in the lung involved altered TLR expression or a deficit in the TLR signaling cascade. We found decreased Toll-like receptor 1 (TLR1) and TLR4 surface expression in HIV-infected U1 monocytic cells compared to the uninfected parental U937 cell line and decreased TLR message in alveolar macrophages (AMs) from HIV-positive subjects. In addition, stimulation with TLR1/2 ligand (Pam(3)Cys) or TLR4 ligand (lipopolysaccharide) resulted in decreased intracellular phosphorylated extracellular signal-regulated kinase and subsequent decreased transcription and expression of TNF-alpha in U1 cells compared to U937 cells. AMs from HIV-positive subjects also showed decreased TNF-alpha production in response to these TLR2 and TLR4 ligands. We postulate that HIV infection alters expression of TLRs with subsequent changes in mitogen-activated protein kinase signaling and cytokine production that ultimately leads to deficiencies of innate immune responses that predispose HIV-positive subjects to infection.

Are immunosuppressive medications associated with decreased responses to routine immunizations? A systematic review.

BACKGROUND: Long-term immunosuppressive medications are being used more commonly for a variety of medical conditions, including immune-mediated diseases and organ transplantation. While these medications are often necessary, they are associated with an increased risk of serious infections. Vaccination may be a way to prevent a variety of infections but vaccine responses among patients receiving immunosuppressive therapies have been variable. PURPOSE: To systematically review the literature describing immune responses among patients on immunosuppressive therapies to vaccinations including influenza, pneumococcal, meningococcal, hepatitis A and B, tetanus toxoid, pertussis, varicella, and zoster. DATA SOURCES: English language citations in the MEDLINE and EMBASE databases from 1985 to 2010. STUDY SELECTION: Two reviewers independently screened titles and abstracts to identify prospective, controlled studies reporting pre- and post-vaccination titers of recommended vaccines in patients receiving long-term immunosuppressive therapies for full-text review. DATA EXTRACTION: Three reviewers independently assessed study characteristics including treatment regimens and pre- and post-vaccination titers. DATA SYNTHESIS: Of the 972 identified titles, fifteen met inclusion criteria. Ten studies assessed the effects of immunosuppressive medications on responses to influenza vaccine, four studies investigated responses following pneumococcal vaccination, and one study assessed both influenza and pneumococcal vaccination. Five of the studies that evaluated influenza vaccination showed partially diminished responses among individuals receiving immunosuppressive therapies, while one of the pneumococcal vaccine studies showed significantly decreased responses following vaccination. Patients treated with more than one immunosuppressive medication were the least likely to respond to vaccination. LIMITATIONS: The heterogeneity of reported outcomes limits generalizeability. CONCLUSIONS: Immunosuppressive therapy, particularly combination regimens, may blunt response to influenza and pneumococcal vaccinations. To ensure the best chance of response, immunizations should be administered prior to initiation of immunosuppressive medications whenever possible.