The Importance of New EBMT Criteria on the Diagnosis of Veno-Occlusive Liver Disease in Children.

BACKGROUND: Early recognition and specific therapy facilitate a favorable disease course in hepatic venous-occlusive disease (HVOD) following hematopoietic stem cell transplantation (HCT). Diagnostic and classification criteria, published by the European Society for Blood and Marrow Transplantation (EBMT), better account for clinical differences in disease presentation in pediatric populations. OBJECTIVES: To compare the course of HVOD in children before and after the implementation of new EBMT criteria. MATERIAL AND METHODS: The study retrospectively evaluates 26 HVODs in 179 children treated in a single HCT unit (Slovakia) comparing the period of 2014-2017 using the Baltimore and modified Seattle criteria with the period of 2018-2021, when new EBMT criteria were adopted. RESULTS: No difference in HVOD incidence (11.2% vs. 14.8%, p = 0.46) and in time of diagnosis post-HCT (15.6 days vs. 15.7 days, p = 0.75) was found. With EBMT criteria we observed more frequent anicteric disease at diagnosis (50% vs. 87.5%, p = 0.04), lower serum bilirubin at diagnosis (3.4 mg/dL vs. 1.23 mg/dL, p = 0.045), and non-significant trends of shorter defibrotide treatment (21.7 days vs. 15.6 days, p = 0.73), decreased mortality (30% vs. 6.2%, p = 0.10) and shorter hospitalization (73.1 days vs. 59.6 days, p = 0.54). CONCLUSIONS: Different time periods around the implementation of new criteria are evaluated, underling that pediatric EBMT criteria for post-transplant HVOD diagnosis appear more sensitive.

Upgraded Cherenkov time-of-flight detector for the AFP project.

We present the results of our performance studies of the upgraded Cherenkov time-of-flight (ToF) detector for the AFP (ATLAS Forward Proton) project. The latest version consists of solid L-shaped fused silica bars, new customized ALD-coated micro-channel plate photomultipliers (MCP-PMTs) miniPlanacon XPM85112-S-R2D2 with an extended lifetime which operate at low gains (order of 103), and an updated construction. The improvements were aimed to increase the efficiency, the lifetime as well as the radiation hardness of the detector which has been designed to operate in high radiation areas (above 400 kGy/year). The detector was finally tested at the CERN-SPS test-beam facility (120 GeV π+ particles) in August 2021 prior to its installation at the Large Hadron Collider (LHC) at CERN. Measurements proved the detector kept its inner timing resolution of 20 ps despite the rather low gain of its photodetector and reduced optical throughput caused by inevitable changes in the detector geometry.

Management of Chronic Graft-vs.-Host Disease in Children and Adolescents With ALL: Present Status and Model for a Personalised Management Plan.

Herein we review current practice regarding the management of chronic graft-vs.-host disease (cGvHD) in paediatric patients after allogeneic haematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukaemia (ALL). Topics covered include: (i) the epidemiology of cGvHD; (ii) an overview of advances in our understanding cGvHD pathogenesis; (iii) current knowledge regarding risk factors for cGvHD and prevention strategies complemented by biomarkers; (iii) the paediatric aspects of the 2014 National Institutes for Health-defined diagnosis and grading of cGvHD; and (iv) current options for cGvHD treatment. We cover topical therapy and newly approved tyrosine kinase inhibitors, emphasising the use of immunomodulatory approaches in the context of the delicate counterbalance between immunosuppression and immune reconstitution as well as risks of relapse and infectious complications. We examine real-world approaches of response assessment and tapering schedules of treatment. Furthermore, we report on the optimal timepoints for therapeutic interventions and changes in relation to immune reconstitution and risk of relapse/infection. Additionally, we review the different options for anti-infectious prophylaxis. Finally, we put forth a theory of a holistic view of paediatric cGvHD and its associated manifestations and propose a checklist for individualised risk evaluation with aggregated considerations including site-specific cGvHD evaluation with attention to each individual's GvHD history, previous medical history, comorbidities, and personal tolerance and psychosocial circumstances. To complement this checklist, we present a treatment algorithm using representative patients to inform the personalised management plans for patients with cGvHD after HSCT for ALL who are at high risk of relapse.

Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis.

Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)-an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO-control, AIA-untreated adjuvant-induced arthritis, AIA-BIL-adjuvant-induced arthritis administrated UCB, CO-BIL-control with administrated UCB. UCB was administered intraperitoneally 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of Mycobacterium butyricum in incomplete Freund's adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic.

Current Prophylaxis and Treatment Approaches for Acute Graft-Versus-Host Disease in Haematopoietic Stem Cell Transplantation for Children With Acute Lymphoblastic Leukaemia.

Acute graft-versus-host disease (aGvHD) continues to be a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). However, higher event-free survival (EFS) was observed in patients with acute lymphoblastic leukaemia (ALL) and grade II aGvHD vs. patients with no or grade I GvHD in the randomised, controlled, open-label, international, multicentre Phase III For Omitting Radiation Under Majority age (FORUM) trial. This finding suggests that moderate-severity aGvHD is associated with a graft-versus-leukaemia effect which protects against leukaemia recurrence. In order to optimise the benefits of HSCT for leukaemia patients, reduction of non-relapse mortality-which is predominantly caused by severe GvHD-is of utmost importance. Herein, we review contemporary prophylaxis and treatment options for aGvHD in children with ALL and the key challenges of aGvHD management, focusing on maintaining the graft-versus-leukaemia effect without increasing the severity of GvHD.

Performance studies of new optics for the time-of-flight detector of the AFP project.

We present the results of performance studies of the upgraded optical part of the time-of-flight subdetector prototype for the AFP (ATLAS Forward Proton) detector obtained during the test campaign in a synchrotron test-beam facility with 5 GeV electrons at the DESY laboratory (Hamburg, Germany) in June 2019. The detection of the particle arrival time is based on generation of Cherenkov light in an L-shaped fused silica bar. In the previous version of the ToF, all bars were made of two pieces (radiator and light guide) glued together with a dedicated glue (Epotek 305). This solution suffers from additional radiation damage of glue. We adopted a new technique of bar production without the need of glue. The new bars have a higher optical throughput by a factor of 1.6, reduced fragility, and better geometrical precision.

A case of Exophiala dermatitidis infection in a child after allogeneic stem cell transplantation: case report and literature review of paediatric cases.

Introduction.Exophiala dermatitidisis a relatively common environmental black yeast with worldwide distribution and is a rare cause of fungal infection, mostly in patients with certain predisposing factors. Due to the rarity of the infection, little is known about the specific predisposing factors, way of infection or treatment. Case presentation. Here, we report what is to our knowledge the first case of E. dermatitidis infection in a child after allogeneic stem cell transplantation. We also review all paediatric cases reported in the literature since 1993. Conclusion. This is, to our knowledge, the first reported case of E. dermatitidis infection in a child after allogeneic stem cell transplantation. This report should increase the awareness of E. dermatitidis in immunocompromised paediatric patients, particularly after stem cell transplantation.

The effect of oregano essential oil on microbial load and sensory attributes of dried meat.

BACKGROUND: Microbial load can be controlled using either synthetic or natural preservatives. Particular interest has been focused on the potential application of plant essential oils as safer additives for meat. However, there is no published research on the use of essential oils during the meat drying process. This study was focused on enhancing the meat drying process by using oregano essential oil (OEO) to inhibit the growth of bacteria and thus obtain a value-added dried meat product. The sensory response from assessors is presented. RESULTS: It was found that the application of OEO in meat was effective in inhibiting Salmonella enteritidis and Escherichia coli. After 6 h of drying at 55 °C, 2 mL (0.038 mL L-1 air) and 1.5 mL (0.028 mL L-1 air) of OEO were considered as the minimal inhibitory concentrations (MICs) against S. enteritidis and E. coli respectively. Samples treated with 0.75 mL of OEO were more attractive for consumption compared with the control; at a higher concentration of OEO, the sensory quality of the food was affected. CONCLUSION: A value-added dried meat product obtained by using OEO to enhance food safety received an acceptable sensory response from consumers. © 2016 Society of Chemical Industry.

Targeted inhibition of the MAPK pathway: emerging salvage option for progressive life-threatening multisystem LCH.

Single-agent vemurafenib leads to a rapid and sustained clinical response in severe multisystem LCH but does not eradicate the disease.Longitudinal assessment of BRAF V600E during treatment shows that clinical remission can occur despite significant amounts of mutated BRAF.

Post-vaccination anti-human papillomavirus antibody seroprevalence among Czech teenaged girls and women.

OBJECTIVE: To evaluate seroprevalence among Czech girls and women previously vaccinated against human papillomavirus (HPV). METHODS: A commercial enzyme-linked immunosorbent assay was used to determine the level of antibodies and seropositivity, with no genotype specification. RESULTS: A group of 356 teenaged girls and women with a mean age of 19.5 years (95% confidence interval [CI], 18.9-20.1 years) was found to have 94.1% HPV seropositivity (95% CI, 91.1%-96.3%) up to 3.5 years after vaccination. The vaccine-specific total seropositivity rates were 98.0% and 85.0% among quadrivalent vaccinees (Gardasil; Merck, Whitehouse Station, NJ, USA) and bivalent vaccinees (Cervarix; GlaxoSmithKline, Brentford, UK), respectively. Adjusting for age and post-vaccination time period, an expected 2:1 (quadrivalent:bivalent) ratio of the geometric mean concentrations of total HPV-specific antibodies induced by the vaccines was observed. The antibody avidity remained almost unchanged up to 3.5 years later. Nevertheless, the mean avidity index was significantly higher among quadrivalent vaccinees (2.50 M GuHCl/mL; 95% CI, 2.42-2.58 M GuHCl/mL) than bivalent vaccinees (2.09 M GuHCl/mL; 95% CI, 2.01-2.17 M GuHCl/mL). CONCLUSION: High anti-HPV seroprevalence at a level related to the valency of vaccine used was achieved among Czech teenaged girls and women up to 3.5 years after vaccination.

Both sublingual and supralingual routes of administration are effective in long-term allergen-specific immunotherapy.

The aim of this study was to confirm or refute the difference between efficacy of long-term specific immunotherapy (SIT) with standardized allergen vaccine consisting of six grass pollens (oat grass, orchard grass, fescue, rye grass, timothy grass, and rye) administered either by sublingual or by supralingual route. To investigate clinical and immunologic changes, 51 patients of a previous 1-year double-blind, placebo-controlled, randomized study were enrolled in an open randomized study that continued over the next 3 years. Sublingual or supralingual immunotherapy (SLIT) was performed in the same way, keeping the drops under or on the tongue, respectively, for 1-2 minutes before swallowing them. Data about symptoms scores and rescue medication intake during grass pollen seasons, as well as skin-prick test results, levels of specific IgG, and IgE antibodies were collected after each pollen season. It was clearly shown that both routes of administration were effective, leading to a significant decrease of clinical symptoms of grass pollen allergy after SIT lasting 3-4 years. No statistically significant difference between sublingually and supralingually treated patients was observed at the end of the study. Adverse effects were limited to a small number of generally mild local and/or systemic reactions with no significant difference between both administration ways of SIT. The significant therapeutic effect of both SLIT and supralingual immunotherapy lasting 3-4 years was clearly achieved. Despite no significant difference between efficacy of both administration ways of SIT, the onset of sublingual SIT effect seems to be slightly faster than that of supralingual SIT.