Augmenter of Liver Regeneration Reduces Ischemia Reperfusion Injury by Less Chemokine Expression, Gr-1 Infiltration and Oxidative Stress

Hepatic ischemia reperfusion injury (IRI) is a major complication in liver resection and transplantation. Here, we analyzed the impact of recombinant human augmenter of liver regeneration (rALR), an anti-oxidative and anti-apoptotic protein, on the deleterious process induced by ischemia reperfusion (IR). Application of rALR reduced tissue damage (necrosis), levels of lipid peroxidation (oxidative stress) and expression of anti-oxidative genes in a mouse IRI model. Damage associated molecule pattern (DAMP) and inflammatory cytokines such as HMGB1 and TNF alpha, were not affected by rALR. Furthermore, we evaluated infiltration of inflammatory cells into liver tissue after IRI and found no change in CD3 or gamma delta TCR positive cells, or expression of IL17/IFN gamma by gamma delta TCR cells. The quantity of Gr-1 positive cells (neutrophils), and therefore, myeloperoxidase activity, was lower in rALR-treated mice. Moreover, we found under hypoxic conditions attenuated ROS levels after ALR treatment in RAW264.7 cells and in primary mouse hepatocytes. Application of rALR also led to reduced expression of chemo-attractants like CXCL1, CXCL2 and CCl2 in hepatocytes. In addition, ALR expression was increased in IR mouse livers after 3 h and in biopsies from human liver transplants with minimal signs of tissue damage. Therefore, ALR attenuates IRI through reduced neutrophil tissue infiltration mediated by lower expression of key hepatic chemokines and reduction of ROS generation

Ectopic Atrial Tachycardia in a 12-Month-Old Girl Treated With Ivabradine and Beta-Blocker, a Case Report

We report on a 12-month-old girl with an ectopic atrial tachycardia successfully treated with the combination of a beta blocking agent and Ivabradine that acts on cardiac pacemaker cells by selectively inhibiting the I(f)channel. Standard therapy had failed to control the tachycardia before. No side effects attributable to Ivabradine were noticed. Due to its mechanism of action Ivabradine is a promising novel agent for the therapy of tachycardia due to increased automaticity. Reports on the use of Ivabradine in young children or infants are rare, but show promising results for congenital junctional ectopic tachycardia. This report adds the second case of ectopic atrial tachycardia in this age group and novel treatment with Ivabradine to the literature

Interleukin-1ß Attenuates Expression of Augmenter of Liver Regeneration (ALR) by Regulating HNF4α Independent of c-Jun

Inflammasomes and innate immune cells have been shown to contribute to liver injury, thereby activating Kupffer cells, which release several cytokines, including IL-6, IL-1ß, and TNFα. Augmenter of liver regeneration (ALR) is a hepatotropic co-mitogen that was found to have anti-oxidative and anti-apoptotic properties and to attenuate experimental non-alcoholic fatty liver disease (NAFLD) and cholestasis. Additionally, hepatic ALR expression is diminished in patients with NAFLD or cholestasis, but less is known about the mechanisms of its regulation under these conditions. Therefore, we aimed to investigate the role of IL-1ß in ALR expression and to elucidate the molecular mechanism of this regulation in vitro. We found that ALR promoter activity and mRNA and protein expression were reduced upon treatment with IL-1ß. Early growth response protein-1 (Egr-1), an ALR inducer, was induced by IL-1ß but could not activate ALR expression, which may be attributed to reduced Egr-1 binding to the ALR promoter. The expression and nuclear localization of hepatocyte nuclear factor 4 α (HNF4α), another ALR-inducing transcription factor, was reduced by IL-1ß. Interestingly, c-Jun, a potential regulator of ALR and HNF4α, showed increased nuclear phosphorylation levels upon IL-1ß treatment but did not change the expression of ALR or HNF4α. In conclusion, this study offers evidence regarding the regulation of anti-apoptotic and anti-oxidative ALR by IL-1ß through reduced Egr-1 promoter binding and diminished HNF4α expression independent of c-Jun activation. Low ALR tissue levels in NAFLD and cholestatic liver injury may be caused by IL-1ß and contribute to disease progression

Parents’ intention to get vaccinated and to have their child vaccinated against COVID-19: cross-sectional analyses using data from the KUNO-Kids health study

A COVID-19 vaccine can be an important key for mitigating the spread of the pandemic, provided that it is accepted by a sufficient proportion of the population. This study investigated parents’ intention to get vaccinated and to have one’s child vaccinated against COVID-19. In May 2020, 612 parents participating with their child in the KUNO-Kids health study completed an online survey. Multivariable logistic regression models were calculated to analyze predictors of intention to vaccinate. Fifty-eight percent of parents intended to get vaccinated against COVID-19, and 51% intended to have their child vaccinated. Significant predictors for the intention to get vaccinated and for having the child vaccinated included stronger parental confidence in one’s knowledge about prevention measures and lower beliefs that policy measures were exaggerated. Conclusion: COVID-19 vaccination hesitancy was considerable in our sample of parents in Germany. However, our study revealed some potentially modifiable factors which should be addressed by a comprehensive and tailored communication and education strategy

Veno-arterial extracorporeal membrane oxygenation support for severe cardiac failure in a pediatric patient with intracranial hemorrhage after spontaneous aneurysmatic rupture

Introduction: Extracorporeal life support in adult patients with extended intracranial hemorrhage is controversial. In pediatric patients, it has traditionally been considered a contraindication as systemic anticoagulation may worsen the hemorrhage and neurological outcome. Case history: We present a nine-year-old female patient who was admitted with extended intracranial hemorrhage after spontaneous rupture of an aneurysm. On day four after the emergency craniotomy, she required veno-arterial extracorporeal membrane oxygenation for septic shock. Using an adapted anticoagulation protocol aimed at lower activated partial thromboplastin time target values, we did not observe any new bleeding or clotting complications during systemic anticoagulation and the patient had good neurological recovery. Conclusion: Extracorporeal life support with low dose systemic anticoagulation can be considered as a treatment option in pediatric patients after craniotomy for intracranial aneurysmatic hemorrhage

Surveillance of acute SARS-CoV-2 infections in elementary schools and daycare facilities in Bavaria, Germany (09/2020–03/2021)

Introduction: Here we report our results of a multi-center, open cohort study ("COVID-Kids-Bavaria") investigating the distribution of acute SARS-CoV-2 infections among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany. Materials and Methods: Overall, 2,568 children (1,337 school children, 1,231 preschool children) and 1,288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7,062 throat swabs were analyzed for SARS-CoV-2 by commercial RT-PCR kits. Results: In phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. Correlation of a positive PCR test result with the local-7-day incidence values showed a strong association of a 7-day-incidence of more than 100/100,000 as compared to <100/100,000 (OR = 10.3 [1.5-438], p < 0.005). After phase III, antibody testing was offered to 713 study participants in elementary schools. A seroprevalence rate of 7.7% (students) and 4.5% (teachers) was determined. Discussion: During the initial waves of the SARS-CoV-2 pandemic, the risk of a positive SARS-CoV-2 result correlated positively with the local 7-day incidence. Hence, the occurrence of SARS-CoV-2 infections were reflected in schools and daycare facilities. An increased risk of SARS-CoV-2 transmission in the setting of daycare and elementary schooling was unlikely

Basiliximab in pediatric liver transplantation: A pharmacokinetic-derived dosing algorithm

The pharmacokinetics and immunodynamics of basiliximab were assessed in 37 pediatric de novo liver allograft recipients to rationally design a dose regimen for this age-group. In part one of the study, patients were given 12 mg/m 2 basiliximab by bolus intravenous injection after organ perfusion and on day 4 after transplant. An interim pharmacokinetic evaluation supported a fixed-dose approach for part two of the study in which infants and children received two 10-mg doses of basiliximab and adolescents received two 20-mg doses. Blood samples were collected over a 12-week period for screening for anti-idiotype antibodies and analysis of basiliximab and soluble interleukin-2 receptor (IL-2R) concentrations. Basiliximab clearance in infants and children  5 L of ascites fluid drainage tended to have lower systemic exposure to basiliximab. CD25-saturating basiliximab concentrations were maintained for 27 ± 9 days in part one of the study (mg/m 2 dosing) with infants exhibiting the lowest durations. CD25 saturation lasted 37 ± 11 days in part two of the study, based on the fixed-dose regimen (p = 0.004 vs. mg/mg 2 dosing), but did not show the age-related bias observed in part one of the study. Anti-idiotype antibodies were detected in four patients, but this did not influence the clearance of basiliximab or duration of CD25 saturation. All 40 enrolled patients were included in the intent-to-treat clinical analysis. Episodes of acute rejection occurred in 22 patients (55%) during the first 12 months post-transplant. Three patients experienced loss of their graft as a result of technical complications, and six patients died during the 12-month study. Basiliximab was well tolerated by intravenous bolus injection, with no cytokine-release syndrome or other infusion-related adverse events. Hence, basiliximab was safe and well tolerated in pediatric patients undergoing orthotopic liver transplantation. To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients < 35 kg in weight should receive two 10-mg doses and those ≥ 35 kg should receive two 20-mg doses of basiliximab by intravenous infusion or bolus injection. The first dose should be given within 6 h after organ perfusion and the second on day 4 after transplantation. A supplemental dose may be considered for patients with a large volume of drained ascites fluid relative to body size.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72080/1/j.1399-3046.2002.01086.x.pd

Successful auxiliary two-staged partial resection liver transplantation (ASPIRE-LTx) for end-stage liver disease to avoid small-for-size situations

Background Risks for living-liver donors are lower in case of a left liver donation, however, due to lower graft volume, the risk for small-for-size situations in the recipients increases. This study aims to prevent small-for-size situations in recipients using an auxiliary two-staged partial resection liver transplantation (LTX) of living-donated left liver lobes. Case presentation Two patients received a two-stage auxiliary LTX using living-donated left liver lobes after left lateral liver resection. The native extended right liver was removed in a second operation after sufficient hypertrophy of the left liver graft had occurred. Neither donor developed postoperative complications. In both recipients, the graft volume increased by an average of 105% (329 ml to 641 ml), from a graft-to-body-weight ratio of 0.54 to 1.08 within 11 days after LTX, so that the remnant native right liver could be removed. No recipient developed small-for-size syndrome; graft function and overall condition is good in both recipients after a follow-up time of 25 months. Conclusions Auxiliary two-staged partial resection LTX using living-donor left lobes is technically feasible and can prevent small-for-size situation. This new technique can expand the potential living-donor pool and contributes to increase donor safety