INFORMER: A System for Immediate and Direct Notification of Critical Data for Patient Care [abstract]

Computational Infrastructure and Informatics Poster SessionEfficient and timely delivery of healthcare requires constant improvements in the quality while keeping the cost of delivery under control. One of the important requirements for such delivery system is the timely notification of patient related data (For example notification of laboratory results on metabolites, circulating levels of certain medications, etc) to doctors, nurses, and other medical professionals for prescribing necessary action. Currently, in nearly all hospitals and laboratories, laboratory or nursing staff are responsible for manually transmitting such information. They take the information verbally or written on a piece of paper, on a pad or on some other media to the recipient in one or multiple hops. Such approach, although serves the purpose, has a number of ordinary to serious limitations such as a higher error rate, incorrect destination, security breach, etc., that could endanger patients life. For example, it is quite possible that the person responsible for notification may forget or delay, for a variety of reasons, to notify the doctor or medical staff or may miscommunicate the results; for example instead of sodium of 150, he or she may orally communicate it as 160. It is also possible that the dispatcher may deliver the information to wrong person (security breach), or take too long to deliver the information. These issues are likely to have serious consequences, in particular for institutions that deal with human subjects such as emergency department of the hospitals where rapid notification is essential for saving lives of critically ill patients. For results communication, paging is a commonly used notification methods but it also involves human and any inadvertent delays in reporting critical data to the physician and other medical staff or to the patient can have serious consequences. We claim that automation in data notification will (a) eliminate or minimize such undesirable consequences, (b) will keep the cost down and (c) improve patient care. We are in the process of designing a pervasive system, referred here as “Informer” to automate the notification process. The system will (a) compose the information (test results, recommendations, etc.) to be dispatched in a easy to read format, (b) identify and notify the critical results to the right medical professionals, (b) maintain an active log of automation process for immediate reference, (c) guarantee accurate data delivery, (d) keep the cost down, (e) provide necessary security, (f) work equally well with wired and wireless network, and (g) offer a high scalability. It will be (a) an independent system with plug and play capability, (b) can port to any system (window, Mac, Linux, etc.), and (c) easy to configure for specific needs

INFORMER and Potassium Values: A system to enhance detection, notification, and action upon a threat to patient safety in the emergency department [abstract]

Computational Infrastructure and Informatics Poster SessionBackground: Quick remediation should occur after critically abnormal potassium levels are detected by the medical laboratory in blood from emergency department (ED) patients. Critical potassium levels can be elevated (“HyperK+“) or decreased (“HypoK+“). HyperK+ and HypoK+ can both lead to avoidable patient harm by causing heart rhythm problems, which can be harmful or lethal. Also, Continuous Quality Improvement (CQI) could be enhanced by the creation of an electronic “audit trail” to track these remediations, which involve detection, notification, action-upon, and documentation steps (D1-N-A-D2). HyperK+ and HypoK+ are a logical first target to ameliorate inefficiencies of D1-N-A-D2, because of the frequency of occurrence of these problems in the ED, because the appropriate rapid ED response is clear, and because failures of D1-N-A-D2. can hurt or kill patients. Hypothesis: An automated D1-N-A-D2, plus audit path, can be created, then merged with a to-be-created standing ED order set, to hasten the treatment of HyperK+ and HypoK+. Methods: (1) A standing order set will be adopted, to permit nurses to administer appropriate treatments to patients with either HyperK+ or HypoK+, without prior physician notification. Oral or intravenous potassium, as appropriate, will remediate HypoK+, Administration of insulin plus glucose, calcium, sodium bicarbonate, and sodium polystyrene resin will ameliorate HyperK+. Order sets will be created after input from physician and nursing personnel. (Re-obtaining of blood from patients in whom HyperK+ is thought to be a false positive result, due to hemolysis of the blood sample, will be permitted). (2) “Electronic loop”: Engineers will create an electronic pathway to enable the rapid electronic notification of appropriate medical personnel, after critical HyperK+ or HypoK+ have been detected. This will enable and drive nurses to action. Actions can be electronically audited via review of digital PyxisTM medication administration machine records, matching medication withdrawals for specific patients to specific incidences of HyperK+ and HypoK+. Time to nurse action will be documented. Data during implementation of D1-N-A-D2 will be compared to prior historical control data, to determine whether the newly created process delivers appropriate care more quickly to patients with critically abnormal K+ values. (In addition, it is anticipated that electronic review of laboratory data for the historical controls will reveal total system failures for some patients; some patients with HyperK+ and/or HypoK+ might not have been treated at all for their potassium abnormality during their time in the ED.) Results: Time to treatment for HyperK+ and HypoK+ patients, and % of patients with HyperK+ and HypoK+ who represent total system failures, before vs. after implementation of the pervasive computing protocol, will be determined. Conclusion: It is anticipated that a pervasive computing environment can be created to facilitate implementation of a standing medication order set, to enable more rapid D1-N-A-D2 after critical values of HyperK+ or HypoK+ are detected in the blood of emergency department patients. Also, this environment will decrease the failure-to-treat rate for critical HyperK+ and HypoK+

Mast cell-mediated immune regulation in health and disease

Mast cells are important components of the immune system, and they perform pro-inflammatory as well as anti-inflammatory roles in the complex process of immune regulation in health and disease. Because of their strategic perivascular localization, sensitivity and adaptability to the microenvironment, and ability to release a variety of preformed and newly synthesized effector molecules, mast cells perform unique functions in almost all organs. Additionally, Mast cells express a wide range of surface and cytoplasmic receptors which enable them to respond to a variety of cytokines, chemicals, and pathogens. The mast cell’s role as a cellular interface between external and internal environments as well as between vasculature and tissues is critical for protection and repair. Mast cell interactions with different immune and nonimmune cells through secreted inflammatory mediators may also turn in favor of disease promoting agents. First and forefront, mast cells are well recognized for their multifaceted functions in allergic diseases. Reciprocal communication between mast cells and endothelial cells in the presence of bacterial toxins in chronic/sub-clinical infections induce persistent vascular inflammation. We have shown that mast cell proteases and histamine induce endothelial inflammatory responses that are synergistically amplified by bacterial toxins. Mast cells have been shown to exacerbate vascular changes in normal states as well as in chronic or subclinical infections, particularly among cigarette smokers. Furthermore, a potential role of mast cells in SARS-CoV-2-induced dysfunction of the capillary-alveolar interface adds to the growing understanding of mast cells in viral infections. The interaction between mast cells and microglial cells in the brain further highlights their significance in neuroinflammation. This review highlights the significant role of mast cells as the interface that acts as sensor and early responder through interactions with cells in systemic organs and the nervous system

Use of autogenous internal iliac artery for bridging the external iliac artery after excision of Aspergillus mycotic aneurysm in renal transplant recipients

Repair of vascular defects in the presence of infection remains a challenging task in immunocompromised patients. We report two patients with postrenal transplant Aspergillus mycotic aneurysms of the allograft renal artery involving the external iliac artery which were excised along with the allograft. The defect in the external iliac artery was repaired successfully with interposition of autogenous internal iliac artery graft. Use of an internal iliac artery graft in such settings has been rarely reported in English literature. Autogenous internal iliac artery grafts provide a useful method to bridge the vascular defects created by radical debridement in the presence of fungal infections

A detailed analysis of next generation sequencing reads of microRNA expression in Barrett’s Esophagus: absolute versus relative quantification

Background Next generation sequencing (NGS) is a state of the art technology for microRNA (miRNA) analysis. The quantitative interpretation of the primary output of NGS i.e. the read counts for a miRNA sequence that can vary by several orders of magnitude (1 to 107) remains incompletely understood. Findings NGS (SOLiD 3 technology) was performed on biopsies from 6 Barrett’s esophagus (BE) and 5 Gastroesophageal Reflux Disease (GERD) patients. Read sequences were aligned to miRBase 18.0. Differential expression analysis was adjusted for false discovery rate of 5%. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for 36 miRNA in a validation cohort of 47 patients (27 BE and 20 GERD). Correlation coefficients, accuracy, precision and recall of NGS compared to qRT-PCR were calculated. Increase in NGS reads was associated with progressively lower Cq values, p 1000 vs. 500 vs. 100 vs. <100). The accuracy, precision and recall of NGS to label a miRNA as differentially expressed were 0.71, 0.88 and 0.74 respectively. Conclusion Absolute NGS reads correlated modestly with qRT-PCR but fold changes correlated highly. NGS is robust at relative but not absolute quantification of miRNA levels and accurate for high-throughput identification of differentially expressed miRNA.The current work was supported by a pilot grant from the American Cancer Society (AB and LKC), the American College of Gastroenterology Junior Faculty Development Award (AB) and Hall Family Foundation (LKC)

Human Mast Cells (HMC-1 5C6) Enhance Interleukin-6 Production by Quiescent and Lipopolysaccharide-Stimulated Human Coronary Artery Endothelial Cells

We examined the effect of intact human mast cells (HMC-1 5C6) and their selected mediators on interleukin-6 (IL-6) production and bone morphogenetic protein-2 (BMP-2) expression in human coronary artery endothelial cells (HCAEC) in the presence and absence of lipopolysaccharide (LPS). Scanning electron microscopy showed that HMC-1 5C6 cells adhere to HCAEC in cocultures. Addition of HMC-1 5C6 cells markedly enhanced the IL-6 production by quiescent and LPS-activated HCAEC even at the maximal concentration of LPS. Furthermore, mast cell-derived histamine and proteases accounted for the direct and synergistic effect of mast cells on IL-6 production that was completely blocked by the combination of histamine receptor-1 antagonist and protease inhibitors. Another novel finding is that histamine was able to induce BMP-2 expression in HCAEC. Collectively, our results suggest that endotoxin and mast cell products synergistically amplify vascular inflammation and that histamine participates in the early events of vascular calcification

C3G overexpression in glomerular epithelial cells during anti-GBM-induced glomerulonephritis

The guanine nucleotide exchange factor C3G, along with the CrkII adaptor protein, mediates GTP activation of the small GTPase proteins Rap1 and R-Ras, facilitating their activation of downstream signaling pathways, which had been found to be important in the pathogenesis of glomerulonephritis. We found that expression of C3G protein was upregulated in glomerular epithelial cells in an experimental model of accelerated anti-GBM antibody-induced glomerulonephritis expression. To determine the consequence of its increased expression, we transfected C3G (using adenoviral constructs) into cultured glomerular epithelial cells and measured the activated forms (i.e., GTP-bound) forms of Rap1 and R-Ras. Activation of Rap1 was not affected by C3G; however, the basal level of GTP-bound R-Ras was decreased. Further, C3G over-expression enhanced the activation of R-Ras in response to endothelin. Overexpression of C3G also led to a significant reduction in glomerular epithelial cell spreading and decreased the cells' E-cadherin expression and augmented their migration. We found that C3G was overexpressed in accelerated anti-GBM antibody-induced glomerulonephritis and suggest that this modulates glomerular epithelial cell morphology and behavior

Generalized (\kappa,\mu)-space forms

Generalized (\kappa ,\mu)-space forms are introduced and studied. We examine in depth the contact metric case and present examples for all possible dimensions. We also analyse the trans-Sasakian case.Comment: 20 pages, several changes have been done in this versio

Transforming growth factor-β1 increases albumin permeability of isolated rat glomeruli via hydroxyl radicals

Transforming growth factor-β1 increases albumin permeability of isolated rat glomeruli via hydroxyl radicals.BackgroundTransforming growth factor-β1 (TGF-β1) is a multifunctional cytokine. Glomerular cells and tubular epithelial cells secrete and respond to TGF-β1. A close association between elevated levels of TGF-β1 and the development of glomerulonephritis, glomerulosclerosis, and tubular hypertrophy has been documented. The role of TGF-β1 in proteinuria is not well understood.MethodsIsolated rat glomeruli were incubated in medium alone or with TGF-β1 (1 to 10 ng/mL) and TGF-β1 + 200 U/mL of superoxide dismutase (SOD) or 1 mmol/L of dimethylthiourea (DMTU) scavengers of superoxide and hydroxyl radicals, respectively, for up to 60 minutes at 37°C. Glomerular albumin permeability (Palb) was calculated from the volumetric response of glomeruli to an oncotic gradient using videomicroscopy.ResultsOne or 2.5 ng/mL of TGF-β1 had no effect on Palb (0.18 ± 0.08, N = 17; 0.18 ± 0.079, N = 20 vs. control 0.00 ± 0.06, N = 25), whereas 5 or 10 ng/mL of TGF-β1 caused a significant increase in Palb (0.31 ± 0.09, N = 20; 0.33 ± 0.06, N = 23) within 15 minutes. The effect of 10 ng/mL of TGF-β1 on Palb increased further after 30, 45, or 60 minutes of incubation (0.43 ± 0.06, N = 24; 0.53 ± 0.06, N = 25; 0.74 ± 0.075, N = 21). The TGF-β1–induced increase in Palb (0.75 ± 0.065, N = 15) was blocked by SOD (0.07 ± 0.14 N = 15) or by DMTU (0.04 ± 0.13, N = 15). Incubation of glomeruli with the carrier medium (4N HCl) in which TGF-β1 is dissolved and SOD or DMTU alone did not affect Palb.ConclusionElevated levels of TGF-β1 derived from glomerular or extraglomerular sources are capable of increasing glomerular Palb via superoxide and hydroxyl radicals and may lead to proteinuria in vivo