Citations

ABSTRACTBackground:Inflammatory bowel disease–associated liver diseases (IBD‐LDs) include autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and an overlap syndrome. Prospective unbiased multicenter data regarding the frequency of IBD‐LD in patients with pediatric inflammatory bowel disease (IBD) are lacking. We examined early alanine aminotransferase (ALT) and γ‐glutamyl transpeptidase (GGT) elevations in children diagnosed as having IBD and assessed the likelihood of IBD‐LD.Methods:Data collected from the prospective observational Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry enrolling children of age <16 years within 30 days of diagnosis. AIH, PSC, and overlap syndrome were diagnosed using local institutional criteria.Results:A total of 1569 subjects had liver enzymes available. Of the total, 757 had both ALT and GGT, 800 had ALT only (no GGT), and 12 had GGT only (no ALT). Overall, 29 of 1569 patients (1.8%) had IBD‐LD. IBD‐LD was diagnosed in 1 of 661 (0.15%) of patients with both ALT and GGT ≤ 50 IU/L compared with 21 of 42 (50%) of patients with both ALT and GGT > 50 (odds ratio 660, P < 0.0001). Of the 29 patients with IBD‐LD, 21 had PSC, 2 had AIH, and 6 had overlap syndrome. IBD‐LD was more common in patients with ulcerative colitis and IBD‐unclassified (indeterminate colitis) than in those with Crohn disease (4% vs 0.8%, respectively, P < 0.001).Conclusions:Elevation of both ALT and GGT within 90 days after the diagnosis of IBD is associated with a markedly increased likelihood of IBD‐LD. Both ALT and GGT levels should be measured in all of the pediatric patients newly diagnosed as having IBD.

ObjectivesOur objective was to determine if technical changes combined with radiation safety initiatives reduced the radiation dose delivered to patients during congenital catheterization.BackgroundUse of ionizing radiation is necessary during cardiac catheterization. Minimizing radiation dose, while maintaining clinically useful image quality, is an important safety issue. In our congenital heart center intentional practice changes, including technical changes and provider awareness initiatives, were implemented to decrease radiation dose.MethodsData were retrospectively collected for all procedures involving children and adults with congenital heart disease (CHD) undergoing catheterization over 45 months. Cases were divided into three categories including: noninterventional (NI), simple intervention (SI), and complex intervention (CI). The change in dose was modeled as log of cumulative air kerma (Ka,r). The change in Ka,r was evaluated for each procedural category as well as changes occurring as a function of age and weight.ResultsConsidering all procedures (n = 1,082), Ka,r decreased by 61%. In the NI group (n = 481), Ka,r decreased by 71%. In the SI group (n = 424), Ka,r decreased by 74%. The Ka,r for the 10–17 year old group (n = 125) and those ≥18 years (n = 709) decreased 74 and 67%, respectively. The Ka,r decreased 72 and 66% for those 20–60 kg and ≥60 kg, respectively. Groups not showing significant change in Ka,r included CI, age ≤9 years, and weight ≤20 kg.ConclusionsThrough technical changes and provider awareness initiatives, our institution dramatically reduced the radiation dose in the majority of pediatric and adult CHD patients undergoing cardiac catheterization. © 2014 Wiley Periodicals, Inc.

Abstract Background: The EML4-ALK fusion gene is more frequently found in younger, never smoking patients with lung cancer. Meanwhile, never smokers exposed to secondhand tobacco smoke (SHS) during childhood are diagnosed at a younger age compared with never smoking patients with lung cancer who are not exposed. We, therefore, hypothesized that SHS, which can induce DNA damage, is associated with the EML4-ALK fusion gene. Methods: We compared the frequency of the EML4-ALK fusion gene among 197 never smoker patients with lung cancer with and without a history of exposure to SHS during childhood at Mayo Clinic. Results: The EML4-ALK fusion gene was detected in 33% of cases from never smokers with a history of SHS exposure during childhood, whereas 47% of never smoking lung cancer cases without a history of childhood SHS exposure tested positive for the fusion gene. Conclusions: The EML4-ALK fusion gene is not enriched in tumors from individuals exposed to SHS during childhood. Impact: These data suggest that childhood exposure to SHS is not a significant etiologic cause of the EML4-ALK fusion gene in lung cancer. Cancer Epidemiol Biomarkers Prev; 23(7); 1432–4. ©2014 AACR.

Abstract NK cells possess both effector and regulatory activities that may be important during the antitumor immune response. In fact, the generation of antitumor immunity by the administration of an agonistic mAb against CD137 is NK cell-dependent. In this study, we report that NK cells could be induced by IL-2 and IL-15 to express CD137 and ligation of CD137-stimulated NK cell proliferation and IFN-γ secretion, but not their cytolytic activity. Importantly, CD137-stimulated NK cells promoted the expansion of activated T cells in vitro, demonstrating immunoregulatory or “helper” activity for CD8+CTL. Furthermore, tumor-specific CTL activity against P815 tumor Ags was abrogated following anti-CD137 treatment in NK-depleted mice. We further demonstrate that CD137-stimulated helper NK cells expressed the high-affinity IL-2R and were hyperresponsive to IL-2. Taken together with previous findings that CD137 is a critical receptor for costimulation of T cells, our findings suggest that CD137 is a stimulatory receptor for NK cells involved in the crosstalk between innate and adaptive immunity.

Abstract Interaction between dendritic cells (DCs) and T cells is a prerequisite for the initiation of a T cell response. The molecular nature of this interaction remains to be fully characterized. We report in this work that freshly isolated mouse splenic DCs and bone marrow-derived DCs express CD137 on the cell surface and in soluble form. Triggering CD137 increased the secretion of IL-6 and IL-12 from DCs. More importantly, infusion of an agonistic mAb to CD137 into naive mice enhanced the ability of DCs to stimulate T cell proliferation in response to both alloantigens and a nominal Ag in vitro. This enhancement of DC function is not mediated through activation of T cells, because the effect was also observed in RAG-1 knockout mice that lack T cells. Our findings implicate CD137 as an important receptor involved in the modulation of DC function.

ABSTRACT Piperacillin-tazobactam (PTZ) is known to cause false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA), due to contamination with galactomannan (GM). We tested 32 lots of PTZ and 27 serum specimens from patients receiving PTZ. GM was not detected in the lots of PTZ; one serum specimen (3.7%) was positive. PTZ formulations commonly used in the United States today appear to be a rare cause for false-positive GM results.

ABSTRACTBackgroundThere is a paucity of data on the temporal trends of cardiovascular risk factors in patients undergoing percutaneous coronary intervention (PCI). We investigated the secular trends of risk profiles of patients undergoing PCI without prior history of cardiovascular disease (CVD).HypothesisCVD risk factors are changed over time.MethodsThis time‐trend analysis from 1994 to 2010 was performed within the Mayo Clinic PCI Registry. Outcome measures were prevalence of CVD risk factors, including the Framingham risk score (FRS), at the time of admission for PCI.ResultsDuring this period, 12,055 patients without a history of CVD (mean age, 65.0 ± 12.4 years, 67% male) underwent PCI at the Mayo Clinic. Age distribution slightly shifted toward older age (P for trend <0.05), but sex did not change over time. Despite a higher prevalence of hypertension, hypercholesterolemia, and diabetes mellitus over time, actual blood pressure and lipid profiles improved (P for trend <0.001). Over time, FRS and 10‐year CVD risk improved significantly (7.3 ± 3.2 to 6.5 ± 3.3, P for trend <0.001; and 11.0 to 9.0, P for trend <0.001, respectively). Body mass index, not included in the FRS, increased significantly (29.0 ± 5.2 to 30.1 ± 6.2 kg/m2, P for trend <0.001), whereas smoking prevalence did not change.ConclusionsThe current study demonstrates that although traditional FRS and its associated predicted 10‐year cardiovascular risk declined over time, the prevalence of risk factors increased in patients undergoing PCI. The study suggests the need for a new risk‐factor assessment in this patient population.

AbstractAlthough coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult‐onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P < 0.01). Dystonia classification included cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw‐opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult‐onset primary dystonia.