Single-Pass Albumin Dialysis in the Treatment of Children with Liver Failure

Background and Aims: Acute and acute on chronic liver failure are life-threatening conditions, and bridging to transplantation is complicated by a paucity of suitable organs for children. While different modalities of extracorporeal liver support exist, their use in children is complicated by a large extracorporeal volume, and data on their use in children is limited. The aim of this analysis was to investigate the efficacy and safety of single-pass albumin dialysis (SPAD) in children with liver failure. Methods: Retrospective medical chart review of pediatric patients with liver failure treated with SPAD. The decrease in hepatic encephalopathy (HE) and the serum levels of bilirubin and ammonia were measured to determine efficacy. Adverse events were documented to assess safety. Results: Nineteen pediatric patients with a median age of 25.5 months and a median body weight of 11.9 kg were treated with SPAD between January 2011 and March 2018. Total bilirubin (p < 0.001) and ammonia (p = 0.02) significantly decreased after treatment with SPAD. As clinical outcome parameter, HE significantly improved (p = 0.001). Twelve patients were bridged successfully to liver transplantation. In all patients, 71 SPAD sessions were run. Clotting in the dialysis circuit was observed in 49% of all sessions. Heparin and citrate were used for anticoagulation and were significantly superior to dialysis without any anticoagulation (p= 0.03). Transfusion of packed blood cells (57%) and catecholamine therapy (49%) were frequently necessary. Conclusions: Treatment with SPAD was effective in detoxification, as measured by significant improvement of HE and clearance from surrogate laboratory parameters

The Second European Service Module (ESM-2) Evolutions, Production and Challenges

This paper presents an overview of the Second European Service Module (ESM-2), the second in a series of European Service Modules produced as part of the Barter agreement between NASA and ESA for the Orion Program. The European Industrial consortium is led by the ESA prime contractor Airbus Defence and Space in Bremen. ESA and Airbus signed the ESM-2 contract on 16 February 2017, for this key element of the Orion Exploration Mission 2 (EM-2). EM-2 is the first crewed mission for Orion and will take astronauts farther into the solar system than humanity has ever travelled. EM-2 will also be a historic mission for Europe, as the ESM-2 will be the first European spacecraft to be part of a human transportation system carrying humans beyond low Earth orbit. ESM-2 is mainly a recurring production following ESM-1. Nevertheless, there are a number of important changes being implemented, for example, to incorporate upgrades to further enhance safety and reliability. The challenging delivery schedule for ESM-2 has driven the need to commence manufacturing prior to completion of the qualification on ESM-1. In addition, some requirement deviations and non-compliances approved for ESM-1 have resulted in modifications for ESM-2. In order to manage the competing constraints effectively, the ESM-2 Team has put in place a number of novel approaches to manage schedule, risk, and technical changes. Airbus has set up multi-functional teams according to an approach known as "Major Spacecraft Deliveries" consisting of quality assurance, engineering and procurement. The risk of starting manufacturing prior to qualification is managed through a special risk share agreement. This agreement necessitates rigorous risk reviews across the board for all manufacturing, assembly, integration and test milestones. The ESM-2 changes are managed by Configuration Management, but Airbus has also introduced the Technical Baseline Matrix to provide a transparent top-level overview of the changes from ESM-1 to ESM-2. The tool provides the basis for ESM-2 design and development needs, decisions, as well as the input for the Orion EM-2 Critical Design Review (CDR). The main technical evolutions, status of the production and the novel management approaches for ESM-2 are presented and discussed in the paper

Sorgende Angehörige als Adressat_innen einer vorbeugenden Pflegepolitik: eine intersektionale Analyse (PflegeIntersek)

Im Mittelpunkt dieser Studie stehen sorgende Angehörige, die sich um Pflegebedürftige mit hohem Hilfebedarf kümmern. Die Pflegenden werden im Hinblick auf Wechselwirkungen zwischen den Differenzkategorien sozioökonomischer Status (SÖS), Geschlecht, Ethnizität sowie Erwerbsstatus untersucht, und es wird nach Unterschieden in der Pflegebewältigung gefragt. Dabei konnten fünf Pflegebewältigungstypen entwickelt werden, wobei drei zu einer ‚eher gelingenden Pflegebewältigung führen, zwei dagegen in einer ‚eher prekären Pflegebewältigung münden. Die Typen differieren in der Art des Zusammenwirkens der genannten Differenzkategorien sowie der Selbstsorgeorientierung der sorgenden Angehörigen. Blickt man auf die Bedarfe, so geht es darum, die Selbstsorgeorientierung und das Selbstsorgehandeln der Sorgenden zu fördern. Dazu ist typenübergreifend im Rahmen einer vorbeugenden Sozialpolitik insbesondere eine frühzeitige zugehende professionelle Pflegebegleitung aus einer Hand im Sinne eines Case-Managements zu empfehlen.The study focuses on caring relatives caring for people in need of long-term care. The caring relatives are analysed with regard to interdependencies between the structural categories socio-economic status, gender, ethnicity, and employment status. We also ask for differences in their coping capacity with regard to elderly care. Five types of coping capacities in longterm-care have been developed, three of these types leading to a rather successful coping strategy, and two types tending to a rather precarious coping situation. The types differ in the way the structural categories interact, and the self-caring orientation of the carers varies, too. Regarding needs and support of caring relatives, their self-caring orientation and self-caring capacity should be strengthened. Across all types, one element of a preventive social policy is highly recommendable: an outreach and professional care assistance from one provider at an early stage in the sense of case-management

Severe infections of Panton-Valentine leukocidin positive Staphylococcus aureus in children

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures

Serum MicroRNA-21 as Marker for Necroinflammation in Hepatitis C Patients with and without Hepatocellular Carcinoma

Background: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC. Methodology/Principal Findings: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = −0.494, P = 0.00002), alanine aminotransferase (ALT) (r = −0.309, P = 0.007), aspartate aminotransferase (r = −0.495, P = 0.000007), bilirubin (r = −0.362, P = 0.002), international normalized ratio (r = −0.338, P = 0.034) and γ-glutamyltransferase (r = −0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dCT of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%. Conclusions/Significance: The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC

miR-198 Inhibits HIV-1 Gene Expression and Replication in Monocytes and Its Mechanism of Action Appears To Involve Repression of Cyclin T1

Cyclin T1 is a regulatory subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is also required for Tat transactivation of HIV-1 LTR-directed gene expression. Translation of Cyclin T1 mRNA has been shown to be repressed in human monocytes, and this repression is relieved when cells differentiate to macrophages. We identified miR-198 as a microRNA (miRNA) that is strongly down-regulated when monocytes are induced to differentiate. Ectopic expression of miR-198 in tissue culture cells reduced Cyclin T1 protein expression, and plasmid reporter assays verified miR-198 target sequences in the 3′ untranslated region (3′UTR) of Cyclin T1 mRNA. Cyclin T1 protein levels increased when an inhibitor of miR-198 was transfected into primary monocytes, and overexpression of miR-198 in primary monocytes repressed the normal up-regulation of Cyclin T1 during differentiation. Expression of an HIV-1 proviral plasmid and HIV-1 replication were repressed in a monocytic cell line upon overexpression of miR-198. Our data indicate that miR-198 functions to restrict HIV-1 replication in monocytes, and its mechanism of action appears to involve repression of Cyclin T1 expression

Serum MicroRNAs as Biomarkers for Hepatocellular Carcinoma in Chinese Patients with Chronic Hepatitis B Virus Infection

BACKGROUND: MicroRNAs (miRNAs) have been shown to anticipate great cancer diagnostic potential. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. The objective of this study was to investigate the potential of serum miRNAs as novel biomarkers for hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: This study was divided into four phases: (I) Ten candidate serum miRNAs were detected by using real-time RT-PCR, corresponding 10 HCC patients with chronic hepatitis B virus (HBV) infection and 10 age- and sex-matched healthy subjects. (II) Marker validation by real-time RT-PCR on HBV patients with (n = 48) or without HCC (n = 48), and healthy subjects (n = 24). (III) Marker detection by real-time RT-PCR in sera from another 14 HCC patients before and 1 month after surgical resection. (IV) We examined the correlation between the expressions of candidate serum miRNAs with clinical parameters of HCC patients. Although miR-222, miR-223 or miR-21 were significantly up- or down-regulated between HCC patients and healthy controls, no significant difference was observed in the levels of these miRNAs between HBV patients without and with HCC. MiR-122 in serum was significantly higher in HCC patients than healthy controls (p<0.001). More importantly, it was found that the levels of miR-122 were significantly reduced in the post-operative serum samples when compared to the pre-operative samples. Although serum miR-122 was also elevated in HBV patients with HCC comparing with those without HCC, the difference was at the border line (p = 0.043). CONCLUSIONS/SIGNIFICANCE: Our results suggest that serum miR-122 might serve as a novel and potential noninvasive biomarker for detection of HCC in healthy subjects, moreover, it might serve as a novel biomarker for liver injury but not specifically for detection of HCC in chronic HBV infection patients

Identification of miRs-143 and -145 that Is Associated with Bone Metastasis of Prostate Cancer and Involved in the Regulation of EMT

The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone. MicroRNAs (miRNAs) play a crucial role in many tumor metastases. The importance of miRNAs in bone metastasis of PCa has not been elucidated to date. We investigated whether the expression of certain miRNAs was associated with bone metastasis of PCa. We examined the miRNA expression profiles of 6 primary and 7 bone metastatic PCa samples by miRNA microarray analysis. The expression of 5 miRNAs significantly decreased in bone metastasis compared with primary PCa, including miRs-508-5p, -145, -143, -33a and -100. We further examined other samples of 16 primary PCa and 13 bone metastases using real-time PCR analysis. The expressions of miRs-143 and -145 were verified to down-regulate significantly in metastasis samples. By investigating relationship of the levels of miRs-143 and -145 with clinicopathological features of PCa patients, we found down-regulations of miRs-143 and -145 were negatively correlated to bone metastasis, the Gleason score and level of free PSA in primary PCa. Over-expression miR-143 and -145 by retrovirus transfection reduced the ability of migration and invasion in vitro, and tumor development and bone invasion in vivo of PC-3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. Their upregulation also increased E-cadherin expression and reduced fibronectin expression of PC-3 cells which revealed a less invasive morphologic phenotype. These findings indicate that miRs-143 and -145 are associated with bone metastasis of PCa and suggest that they may play important roles in the bone metastasis and be involved in the regulation of EMT Both of them may also be clinically used as novel biomarkers in discriminating different stages of human PCa and predicting bone metastasis