Catheter-Directed Thrombolysis for Portal Vein Thrombosis in Children: A Case Series.

PURPOSE: To describe safety and efficacy of catheter-directed thrombolysis (CDT) for portal vein thrombosis (PVT) in children. MATERIALS AND METHODS: Retrospective review was performed of 10 consecutive patients (7 girls, 3 boys; mean age 11.9 y; range, 3-17 y) with PVT undergoing CDT at a single tertiary children's hospital between August 2005 and March 2016. PVT was categorized by etiology and extent (intrahepatic, extrahepatic, or both). CDT was performed with infusion catheters placed via percutaneous transhepatic (PTH) and/or transjugular intrahepatic (TJ) approaches, with or without the use of adjunctive maneuvers, including balloon maceration and suction and rheolytic thrombectomy. Degree of thrombolysis on portal venography, presence of portal vein thrombus on available follow-up imaging, and complication rates were recorded. RESULTS: In 10 patients, 13 CDT procedures were performed for PVT, with 3 patients requiring repeat CDT. Portal access was achieved with PTH (n = 6), TJ (n = 2), or combined (n = 2) approaches. All cases were successful in re-establishing patency and hepatopetal flow on portal venography with complete thrombolysis achieved in 10 of 13 cases (77%). Two major complications (20%) occurred, both with PTH access. Mean follow-up time for 9 patients was 2.6 years (range, 51-1,902 d) with long-term patency achieved in 6 (67%). CONCLUSIONS: CDT can be safe and effective for PVT in children. Portal access considerations and early initiation of thrombolysis may further increase safety and efficacy.

Promoter choice and translational repression determine cell type-specific cell surface density of the inhibitory receptor CD85j expressed on different hematopoietic lineages.

CD85j (ILT2/LILRB1/LIR-1) is an inhibitory receptor that recognizes major histocompatibility complex (MHC) class Ia and Ib alleles that are widely expressed on all cell types. On ligand recognition, CD85j diminishes kinase activity by recruiting phosphatases to motifs within its cytoplasmic domain. Within the hematopoietic system, CD85j is expressed with cell-specific patterns and cell surface densities that reflect the different roles of cell contact-mediated inhibition in these lineages. While monocytes ubiquitously have high cell surface expression, B lymphocytes start to express CD85j at intermediate levels during early B-cell maturation and natural killer (NK) cells and T cells exhibit a low level of expression on only a subset of cells. The cell-specific expression pattern is accomplished by 2 complementing but not independent mechanisms. Lymphocytes and monocytes use distinct promoters to drive CD85j expression. The lymphocyte promoter maps 13 kilobases (kb) upstream of the monocyte promoter; its use results in the inclusion of a distant exon into the 5'-untranslated region. A short sequence stretch within this exon has the unique function of repressing CD85j protein translation and is responsible for the subdued expression in lymphocytes. These cell-specific mechanisms allow tailoring of CD85j levels to the distinct roles it plays in different hematopoietic lineages.

Automation of Educational Tasks for Academic Radiology.

RATIONALE AND OBJECTIVES: The process of education involves a variety of repetitious tasks. We believe that appropriate computer tools can automate many of these chores, and allow both educators and their students to devote a lot more of their time to actual teaching and learning. This paper details tools that we have used to automate a broad range of academic radiology-specific tasks on Mac OS X, iOS, and Windows platforms. Some of the tools we describe here require little expertise or time to use; others require some basic knowledge of computer programming. MATERIALS AND METHODS: We used TextExpander (Mac, iOS) and AutoHotKey (Win) for automated generation of text files, such as resident performance reviews and radiology interpretations. Custom statistical calculations were performed using TextExpander and the Python programming language. A workflow for automated note-taking was developed using Evernote (Mac, iOS, Win) and Hazel (Mac). Automated resident procedure logging was accomplished using Editorial (iOS) and Python. We created three variants of a teaching session logger using Drafts (iOS) and Pythonista (iOS). Editorial and Drafts were used to create flashcards for knowledge review. We developed a mobile reference management system for iOS using Editorial. We used the Workflow app (iOS) to automatically generate a text message reminder for daily conferences. Finally, we developed two separate automated workflows-one with Evernote (Mac, iOS, Win) and one with Python (Mac, Win)-that generate simple automated teaching file collections. RESULTS: We have beta-tested these workflows, techniques, and scripts on several of our fellow radiologists. All of them expressed enthusiasm for these tools and were able to use one or more of them to automate their own educational activities. CONCLUSIONS: Appropriate computer tools can automate many educational tasks, and thereby allow both educators and their students to devote a lot more of their time to actual teaching and learning.

Sedentary Behavior in the Workplace: A Potential Occupational Hazard for Radiologists.

In this study, we sought to quantify the sedentary worklife of the radiologist, a potential health risk. Radiologists of all training levels at our academic institution were surveyed to estimate the levels of at-work and out-of-work sitting. Fitbit One activity monitors were used to measure the at-work activity levels of radiology, pediatric, and internal medicine (IM) residents. Correlation between awareness and utilization of dynamic (sitting or standing, walking, or biking) picture archiving and communication system (PACS) workstations among radiology residents was assessed. Among surveyed radiologists (n = 89), 78% estimated sitting for at least 6 hours per workday. Estimated workplace sitting accounted for most of the total sitting for 81% of respondents. As measured by activity monitors, radiology residents (n = 27) took fewer steps per day (2683 vs 4602 vs 4967) and per hour (294 vs 419 vs 444) and experienced more sedentary time per hour (40.3 vs 36.2 vs 34.9min/h) than IM (n = 15) and pediatric (n = 9) residents. Activity experienced during reading room-based work and interventional work was compared by studying 4 additional radiology residents during both types of rotations. Reading-room activity was low, whereas activity on interventional rotations surpassed average levels for the pediatric and IM residents in our study. Radiology residents' (n = 28) awareness and utilization of dynamic PACS workstations varied among reading rooms, but were generally low-75% reported never or rarely using them. Resident utilization correlated with awareness of dynamic workstations available at our institution (R(2) = 0.64; P = 0.013). In conclusion, radiology residents in our study led more sedentary worklives compared with residents from other specialties and took minimal advantage of available tools to mitigate this. Potential health risks of inactivity justify individual and departmental efforts to limit workplace inactivity among radiologists.

Regulation of T cell receptor signaling by activation-induced zinc influx.

Zinc is a trace element that is essential for innate and adaptive immune responses. In addition to being a structural element of many proteins, zinc also functions as a neurotransmitter and an intracellular messenger. Temporal or spatial changes in bioavailable zinc may influence the activity of several enzymes, including kinases and phosphatases. We provide evidence that zinc functions as an ionic signaling molecule after T cell activation. Cytoplasmic zinc concentrations increased within 1 min after T cell receptor (TCR) triggering, in particular in the subsynaptic compartment. The increase depended on the extracellular zinc concentrations and was inhibited by silencing zinc transporter Zip6. Increased zinc influx reduced the recruitment of SHP-1 to the TCR activation complex, augmented ZAP70 phosphorylation and sustained calcium influx. By calibrating TCR activation thresholds, increased extracellular zinc bioavailability facilitated the induction of T cell proliferative responses to suboptimal stimuli.

T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling.

Intermittent administration of parathyroid hormone (iPTH) is used to treat osteoporosis because it improves bone architecture and strength, but the underlying cellular and molecular mechanisms are unclear. Here, we show that iPTH increases the production of Wnt10b by bone marrow CD8+ T cells and induces these lymphocytes to activate canonical Wnt signaling in preosteoblasts. Accordingly, in responses to iPTH, T cell null mice display diminished Wnt signaling in preosteoblasts and blunted osteoblastic commitment, proliferation, differentiation, and life span, which result in decreased trabecular bone anabolism and no increase in strength. Demonstrating the specific role of lymphocytic Wnt10b, iPTH has no anabolic activity in mice lacking T-cell-produced Wnt10b. Therefore, T-cell-mediated activation of Wnt signaling in osteoblastic cells plays a key permissive role in the mechanism by which iPTH increases bone strength, suggesting that T cell osteoblast crosstalk pathways may provide pharmacological targets for bone anabolism.

T cell subset-specific susceptibility to aging.

With increasing age, the competence of the immune system to fight infections and tumors declines. Age-dependent changes have been mostly described for human CD8 T cells, raising the question of whether the response patterns for CD4 T cells are different. Gene expression arrays of memory CD4 T cells yielded a similar age-induced fingerprint as has been described for CD8 T cells. In cross-sectional studies, the phenotypic changes were not qualitatively different for CD4 and CD8 T cells, but occurred much more frequently in CD8 T cells. Homeostatic stability partially explained this lesser age sensitivity of CD4 T cells. With aging, naïve and central memory CD8 T cells were lost at the expense of phenotypically distinct CD8 effector T cells, while effector CD4 T cells did not accumulate. However, phenotypic shifts on central memory T cells were also more pronounced in CD8 T cells. This distinct stability in cell surface marker expression can be reproduced in vitro. The data show that CD8 T cells are age sensitive by at least two partially independent mechanisms: fragile homeostatic control and gene expression instability in a large set of regulatory cell surface molecules.

Extensive diversity of Ig-superfamily proteins in the immune system of insects.

The extensive somatic diversification of immune receptors is a hallmark of higher vertebrates. However, whether molecular diversity contributes to immune protection in invertebrates is unknown. We present evidence that Drosophila immune-competent cells have the potential to express more than 18,000 isoforms of the immunoglobulin (Ig)-superfamily receptor Down syndrome cell adhesion molecule (Dscam). Secreted protein isoforms of Dscam were detected in the hemolymph, and hemocyte-specific loss of Dscam impaired the efficiency of phagocytic uptake of bacteria, possibly due to reduced bacterial binding. Importantly, the molecular diversity of Dscam transcripts generated through a mechanism of alternative splicing is highly conserved across major insect orders, suggesting an unsuspected molecular complexity of the innate immune system of insects.