Diagnosis and treatment of juvenile myelomonocytic leukemia in Slovak Republic: novel approaches.

Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive clonal myeloproliferative disorder of infancy and early childhood caused by oncogenic mutations in genes involved in the Ras pathway. Long-term survival has only been achieved with hematopoietic stem cell transplantation (HSCT), being able to cure more than 50% patients. To manage the disease before HSCT remains an important issue with constant searching for optimal treatment modalities. According to several retrospective analyses, azacitidine (AZA) induced clinical and molecular responses in patients with relapsed JMML pre-transplant and post-transplant, suggesting its use as a promising "bridging" therapy before HSCT. In this paper we report our first consecutive cohort of patients with JMML treated at our institution as well as our experience with the diagnosis, novel treatment and management of these patients before the HSCT. We present 6 patients with JMML, harboring different somatic mutations (PTPN11 and NRAS), with distinct clinical features; 3 of them had been treated with AZA 75 mg/m2 i.v. on days 1 to 7 of a 28-day cycle before the HSCT. Response to therapy was evaluated after each cycle in accordance with the International response criteria. One patient had a progression of splenomegaly during the treatment and after three cycles he was urgently transplanted. At the present, he is remaining in complete remission 3 years after HSCT. Two patients showed impressive response following the first cycle of the therapy with a regression of splenomegaly and monocyte count, normalized leukocytes, platelets and absent blasts in peripheral blood. The treatment was well tolerated with no adverse effect recorded. The clinical activity and favorable toxicity of AZA in JMML provide a rationale for its use as a "bridging" therapy before HSCT. Prospective trials with accompanying translational studies are required to provide further information regarding individual factors that may direct the most appropriate choice of pretransplantation therapy.

Timing resolution studies of the optical part of the AFP Time-of-flight detector.

We present results of the timing performance studies of the optical part and front-end electronics of the time-of-flight subdetector prototype for the ATLAS Forward Proton (AFP) detector obtained during the test campaigns at the CERN-SPS test-beam facility (120 GeV π+ particles) in July 2016 and October 2016. The time-of-flight (ToF) detector in conjunction with a 3D silicon pixel tracker will tag and measure protons originating in central exclusive interactions p + p → p + X + p, where the two outgoing protons are scattered in the very forward directions. The ToF is required to reduce so-called pileup backgrounds that arise from multiple proton interactions in the same bunch crossing at high luminosity. The background can fake the signal of interest, and the extra rejection from the ToF allows the proton tagger to operate at the high luminosity required for the measurement of the processes. The prototype detector uses fused silica bars emitting Cherenkov radiation as a relativistic particle passes through them. The emitted Cherenkov photons are detected by a multi-anode micro-channel plate photomultiplier tube (MCP-PMT) and processed by fast electronics.

Construction of the optical part of a time-of-flight detector prototype for the AFP detector.

We present the construction of the optical part of the ToF (time-of-flight) subdetector prototype for the AFP (ATLAS Forward Proton) detector. The ToF detector in conjunction with a 3D silicon pixel tracker will tag and measure protons originating in central exclusive interactions p + p → p + X + p, where the two outgoing protons are scattered in the very forward directions. The ToF is required to reduce so-called pileup backgrounds that arise from multiple proton interactions in the same bunch crossing at high luminosity. The background can fake the signal of interest, and the extra rejection from the ToF allows the proton tagger to operate at the high luminosity required for measurement of the processes. The prototype detector uses fused silica bars emitting Cherenkov radiation as a relativistic particle passes through it. The emitted Cherenkov photons are detected by a micro-channel plate multi-anode Photomultiplier Tube (MCP-PMT) and processed by fast electronics.

Hyperbilirubinemia decreases physiological markers in adjuvant-induced arthritis.

There is evidence that a higher serum level of bilirubin (BIL) may be a protective factor for autoimmune diseases. We examined the effect of BIL supplementation in adjuvant-induced arthritis (AIA) where oxidative stress, inflammation and inadequate immune response are present. Male Lewis rats were randomized into groups: CO - control, AIA - untreated adjuvant-induced arthritis, AIA-BIL - adjuvant-induced arthritis administrated BIL (200 mg/kg b.w. daily i.p. during 14 days). Change of hind paw volume in the AIA-BIL group in comparison to the AIA group was significantly decreased after BIL administration. In CO and AIA groups we found almost untraceable levels of BIL. In the AIA-BIL group hyperbilirubinemia was observed. BIL administration significantly decreased plasma levels of C-reactive protein and ceruloplasmin in the AIA-BIL group in comparison to the AIA group. The values of white and red blood cells, hemoglobin and hematocrit were significantly decreased in AIA-BIL after BIL supplementation. Organs like spleen and thymus had a lower weight in AIA-BIL than in AIA. Histological findings showed decreased or even absent damage in hind paw joint of AIA-BIL animals. We observed an immunomodulatory effect of BIL on AIA development, which may also have a novel pharmacological impact.

Design of Cherenkov bars for the optical part of the time-of-flight detector in Geant4.

We present the results of studies devoted to the development and optimization of the optical part of a high precision time-of-flight (TOF) detector for the Large Hadron Collider (LHC). This work was motivated by a proposal to use such a detector in conjunction with a silicon detector to tag and measure protons from interactions of the type p + p → p + X + p, where the two outgoing protons are scattered in the very forward directions. The fast timing detector uses fused silica (quartz) bars that emit Cherenkov radiation as a relativistic particle passes through and the emitted Cherenkov photons are detected by, for instance, a micro-channel plate multi-anode Photomultiplier Tube (MCP-PMT). Several possible designs are implemented in Geant4 and studied for timing optimization as a function of the arrival time, and the number of Cherenkov photons reaching the photo-sensor.

Protothecal peritonitis in child after bone marrow transplantation: case report and literature review of paediatric cases.

The case presented here illustrates a protothecal infection caused by Prototheca wickerhamii in a paediatric haematopoietic stem cell recipient followed by a review of the literature of all 13 paediatric cases published since 1980. Protothecosis is a rare disease caused by algae, not described in this setting before. Infection was proven additionally post-mortem from peritoneal dialysis fluid. Even though no death of a paediatric patient due to this infection has been reported and the mortality rate associated with protothecosis is low, our patient died from multiorgan failure as a result of numerous post-transplant complications and a strain of cultivated alga that was highly resistant to antifungal agents. Prototheca spp. show various susceptibility profiles, and there is no direct correlation between in vitro activity and clinical response. There are different treatment regimens described but there are no clear published guidelines of specific therapy of protothecosis. Paediatric cases were successfully treated mostly with amphotericin B and azoles. As the number of immunocompromised patients increases, it is necessary to think more about unusual pathogens such as Prototheca.

[Perineal audit: reasons for more than one thousand episiotomies]. / Perineální audit: duvody pro více nez 1000 epiziotomií.

AIM: To analyze reasons for episiotomy use in vaginal delivery among obstetricians and midwives. Consecutively, to indentify disputable indications for its use based on published research in order to facilitate the decrease in frequency of this operation, while preserving high quality of obstetrical care. METHODS: Reasons for mediolateral episiotomy use were recorded by obstetricians and midwives after each vaginal delivery with episiotomy at the Ob&Gyn Department of the Charles University Hospital in Pilsen in the period of February 2006 - June 2007. The main reason and all reasons for episiotomy use were evaluated separately. RESULTS: The reason for episiotomy use was recorded in 1069 cases (93%) out of a total of 1150 vaginal deliveries, in which mediolateral episiotomy was performed (42% of all vaginal deliveries). The most common group of main reasons for episiotomy use was a concern about postpartum pelvic floor functional impairment (624, 58% of episiotomies), especially a rigid, non-elastic perineum (401, 37%). Fetal distress (181, 17%) and abnormalities of the expulsive forces/uncooperative parturient (109, 10%) followed. When evaluating all (including secondary) reasons, the most common groups of reasons for episiotomy use were the effort of pelvic floor functionality preservation (871, 50%), abnormalities of the expulsive forces/uncooperative parturient (354, 20%) and fetal distress (253, 15%). When evaluating episiotomies performed by obstetricians and midwives separately, the concern about postpartum pelvic floor functionality prevailed in midwives (81% vs. 39% of episiotomies performed primarily for this reason). Conversely, the obstetricians performed episiotomy more frequently for fetal distress (28% vs. 4%). CONCLUSION: In view of the fact that midwives attend only physiological deliveries in our department, the spectrum of reasons for episiotomy use among midwives is narrower and the concern about postpartum pelvic floor functionality dominates. Currently, the concern about postpartum pelvic floor functionality should not be considered a legitimate indication for episiotomy use. The fact that 624 (58%) episiotomies were performed for this reason represents a significant reserve for a decrease in the frequency of episiotomy use. The reduction should be possible primarily among midwives (81% of all main reasons for episiotomy use in the midwive group, i.e. 37% of all episiotomies performed). The analysis of reasons for episiotomy use is an important step in reduction of episiotomy rates while preserving or improving the standard of treatment provided.

Double-blind, placebo-controlled evaluation of grass pollen specific immunotherapy with oral drops administered sublingually or supralingually.

Forty-one patients suffering from grass pollen allergy underwent specific immunotherapy with standardized allergen extract consisting of six grass pollens (H-Al per os) administered either sublingually or supralingually for one year. In order to investigate clinical and immunological changes induced by the administration of allergens via the oral mucosa, the double-blind, placebo-controlled, randomized design of the trial with 30 other patients enrolled in placebo groups was applied. Specific immunotherapy with oral drops administered sublingually or supralingually was performed in the same way, keeping the drops under or on the tongue, respectively, for 1-2 min before swallowing them; at the end of the trial the cumulative dose of the allergen was almost 20 times higher than that of the subcutaneous therapy with corresponding allergen preparation. Data about symptoms scores and drugs intake during grass pollen season, as well as skin reactivity, levels of specific IgG and IgE antibodies, before the study and after the study's completion, were obtained. It was found that both routes of administration are effective according to subjective clinical parameters and drug consumption, with a highly significant reduction of symptoms and drug intake favoring sublingual administration where a reduction of more than 60% was achieved. Only sublingual active group showed a significant increase in Dactylis glomerata-specific IgG serum levels. Adverse effects were limited to a small number of generally mild local and/or systemic reactions. The results suggest that the administration of allergens via the oral mucosa is safe and clinically effective, favoring the sublingual rather than supralingual route.