Sclerodermatous manifestation of chronic graft versus host disease: therapy challenges

Chronic graft versus host disease (cGHVD) is one of the most serious complications after allogeneic hematopoietic cell transplantation (allo-HCT). It varies in between patients, often leading to systemic and functional limitations. It can be challenging considering the heterogeneity of patients. The objective of this paper is to present clinical aspects of sclerodermatous manifestation of cGVHD as a complication of allo-HCT in pediatric patients. We diagnosed three patients with different sclerodermatous skin involvement and cGVHD features. The treatment applied varied among patients and was based on current available standards of care. We analyzed effectiveness of systemic steroid therapy, extracorporeal photopheresis and ruxolitinib. In conclusion, all patients achieved improvement in skin leasions and quality of life, based on the individualized treatment approach

Relapsed childhood acute myeloid leukemia: prognostic factors and outcomes: experience from a single oncology center

Introduction: Over recent decades, significant progress in the treatment of childhood acute myeloid leukemia (AML) has been made. However, the relapsed disease remains a challenge. The aim of this study was to analyze therapy results in pediatric patients treated for relapsed AML in a single oncology center, with a particular focus on prognostic factors. Materials and methods: Data from patients younger than 19 years with AML diagnosed between January 1994 and December 2020 treated in the Department of Pediatric Hematology and Oncology in Bydgoszcz, Poland was analyzed, with detailed analysis of patients with relapsed disease. Results: A total of 77 children were diagnosed with AML in the analyzed period and 21 had a relapsed disease (27.3%). Bone marrow relapse was the most common. The risk factors of relapse included white blood cells >100 G/L at initial diagnosis and classification to the high risk group. Late relapse was related to poorer outcomes. The 5-year probability of overall survival for the entire group was 28.6%, and this was significantly higher in patients who achieved second remission compared to those who did not (44.9% vs. 0.0%, p <0.001). The main reason for death was progression of disease, which occurred in 10 patients. Conclusions: Outcomes in relapsed AML in children are still dismal. Lack of second remission suggests the need for experimental therapy

Changing risk factors in childhood acute lymphoblastic leukemia: experience from Kujawsko-Pomorski region 1976–2018

Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Risk factors in childhood ALL have changed during recent decades, mostly due to treatment personalization. The aim of this study was to analyze therapy results and prognostic factors in childhood ALL in the Kujawsko-Pomorski region of Poland between 1976 and 2018. Material and methods: Data from 495 patients (0–18 years old) diagnosed with ALL from the Kujawsko-Pomorski region between 1976 and 2018 was analyzed. Prognostic factors were analyzed separately in specific therapeutic groups, which were defined by several therapy protocols. Results: Prognostic factors have changed over the course of consecutive therapeutic periods. Between 1976 and 1988 (the first and second therapeutic protocols), central nervous system involvement was the most important risk factor. During the third therapeutic period, an unsatisfactory treatment response on days 8 and 14 was related to a poor outcome. In 1995–2002, the risk factors were hepatomegaly, splenomegaly, lymph nodes involvement, and unsatisfactory therapy response on days 15 and 33. Between 2002 and 2011, immunophenotype other than ‘common’ and hemoglobin level at diagnosis were the risk factors, and a lack of BCR-ABL aberration was related to better therapy results. During the final analyzed period (2011–2018), failure to achieve remission on day 33 was a risk factor, and patients classified as non-high risk group and those aged <6 years had better outcomes. Conclusions: The changing profile of risk factors in ALL has reflected progress in ALL therapy, with the gradual elimination of factors related to poor outcomes, mostly due to modifications in treatment and the development of diagnostic methods as well as therapy monitoring

High risk of invasive fungal disease in children undergoing hematopoietic cell transplantation or complex anticancer therapy: the adverse role of post-transplant CMV replication

Introduction: We analyzed the epidemiology and outcomes of treatment of invasive fungal disease (IFD) in children during anticancer therapy (PHO, pediatric hematology and oncology) or after hematopoietic cell transplantation (HCT) over a period of eight consecutive years in a single-center study. Material and methods: Overall, a total of 254 HCTs were performed, and 415 children were newly diagnosed for malignancy. Incidence, epidemiology and outcome of IFD were analyzed. Results: The cumulative incidence of any IFD was 32.6% in allo-HCT, 22.2% in PHO, and 6.0% in auto-HCT patients. The incidence of proven +probable IFD was 12.6%, 10.4%, and 6.0%, respectively. As many as 77.0% HCT and 67.4% PHO of fungal episodes occurred in acute leukemia patients: the highest incidence of any IFD was observed for acute lymphoblastic leukemia (29.3% in HCT; 40.5% in PHO) and for acute myeloblastic leukemia (51.1% in HCT; 65.0% in PHO) patients. There were no significant differences in the incidence of fungal infections in both allo-HCT and PHO patients between the 2-year periods. Factors contributing to an increased risk of IFD in allo-HCT patients were: CMV replication, and acute and chronic graft-versus-host disease (GvHD). Survival from IFD was 91.9% in PHO, and 78.1% in HCT patients. Fungal pneumonia in HCT patients resolved in 62.9%, while in PHO patients it resolved in 93.5%. Conclusions: The risk of IFD in allo-HCT patients is much higher than in auto-HSCT and PHO patients. The outcome of IFD is better in PHO and auto-HCT than in allo-HCT settings

Acute non-hematological toxicity of intensive chemotherapy of acute lymphoblastic leukemia in children

IntroductionLeukemia belong to 31% of all childhood malignancies. Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric leukemia accounting for 80–85% of all cases. Progress in diagnostics and therapy of leukemia is dependent on international cooperation. The objective of the study was the analysis of non-hematological toxicity during intensive chemotherapy according to two consecutive intercontinental protocols. Patients and methodsA total number of 210 children diagnosed for ALL who were treated in single center between 2002 and 2018 were divided in two groups defined by therapeutic protocol: ALL IC-BFM 2002 (group 1) and ALL IC-BFM 2009 (group 2). Data were entered prospectively from 2002 into international ALL IC-BFM 2002 and ALL IC-BFM 2009 registry. Non-hematological toxicity was analyzed according to the criteria followed in protocols, compatible with CTCAE criteria. ResultsThe most frequent toxicities included hepatic toxicity with transaminitis and hyperbilirubinemia, infections, oral mucositis and gut toxicity with vomiting, and/or diarrhea. Non-hematological toxicity episodes calculated as a ratio per patient were comparably often observed in both the groups; however, the distribution was different. There were more grade III and less grade II toxicities. This was mainly related to significant increase in the rates of infections and transaminitis. However, there was a significant decrease in vomiting and central and peripheral neurotoxicity. ConclusionsIntensive treatment of ALL is burdened with frequent severe toxic and infectious complications. Further progress in therapy of pediatric ALL is dependent on sophisticated supportive therapy and very well experienced and knowledgeable therapeutic team

Procognitive activity of triazine 5-HT6 receptor antagonists in rats

Celem niniejszej pracy było zbadanie aktywności prokognitywnej nowych ligandów receptora serotoninowego 5-HT6, będących pochodnymi 1,3,5-triazyny w teście rozpoznawania nowego obiektu (NOR) u szczurów. W pracy przebadano pięć związków o symbolach MST 4, TR 12, TR 37, KB 61 i KMP 10. Wszystkie badane związki, podane zwierzętom w dawce 3 mg/kg, wykazały istotną zdolność do odwracania zaburzeń pamięci indukowanych podaniem skopolaminy w teście NOR u szczurów. Uzyskane działanie było silniejsze niż obserwowane dla związku odniesienia – rywastygminy. Analizując zależność struktura-aktywność nowych triazynowych pochodnych można zauważyć, że obecność części hydrofobowej znajdującej się w położeniu 4 1,3,5-triazyny jest istotna dla aktywności ośrodkowej tych substancji. Najsilniejszą aktywność obserwowano dla pochodnej TR 37, która w pozycji meta pierścienia aromatycznego posiada podstawnik chlorkowy oraz dla pochodnych TR 12 i KMP 10, których część hydrofobowa jest znacznie rozbudowana. Otrzymane wyniki wskazują na istotną aktywność farmakologiczną nowych antagonistów receptora 5-HT6. Wydaje się, że warto przeprowadzić dalsze, poszerzone badania, które pozwolą na dokładniejsze określenie ich profilu aktywności ośrodkowej.The aim of this study was to determine procognitive activity of new derivatives of 1,3,5-triazine (MST 4, TR 12, TR 37, KB 61 and KMP 10) which are ligands of serotonin 5-HT6 receptors in the novel object recognition (NOR) test in rats. All of examined compounds showed a significant ability to reverse scopolamine-induced memory impairment in rats after administration at a dose of 3.0 mg/kg. Moreover, their observed procognitive effect was stronger than that of the reference drug – rivastigmine. The structure-activity relationship investigations showed that the presence of hydrophobic moiety in position 4 of 1,3,5-triazine is very important for procognitive activity of tested derivatives. The strongest activity was observed for compound TR 37 which contains chlorine at the meta position of the aromatic ring, and for compounds TR 12 and KMP 10 which have bulky hydrophobic ring. The obtained results indicate significant pharmacological activity of tested compounds. However, further research and extended studies should be conducted to obtain more detailed information about their central activity profile

Seksualny dobrostan a satysfakcja z życia osób z niepełnosprawnością ruchową: moderacyjna rola samooceny

Wstęp: Obecność i postęp niepełnosprawności wymaga od osoby nią dotkniętą nowego sposobu funkcjonowania, który charakteryzuje się ograniczonymi możliwościami zmagania się z problemami dnia codziennego. Metaanalizy badań pokazują, że nabycie lub posiadanie niepełnosprawności fizycznej może w negatywny sposób kształtować nasza samoocenę i ogólny dobrostan. Wyniki zawarte w dostępnych publikacjach wskazują na związki między samooceną, satysfakcją seksualną i dobrostanem wśród osób z niepełnosprawnością fizyczną. Celem niniejszej pracy jest zweryfikowanie roli samooceny w relacji pomiędzy dobrostanem seksualnym a satysfakcją z życia osób z niepełnosprawnością motoryczną Materiały i metody: W badaniu wzięło udział 85 osób: 50 kobiet i 35 mężczyzn w przedziale wiekowym od 18. do 65. roku życia (M=32,49; SD=10,93). Badani wypełniali 3 kwestionariusze psychologiczne. Wykorzystano Skalę Samooceny autorstwa Rosenberga, Krótką Skalę Dobrostanu Seksualnego autorstwa Gerymskiego oraz Skalę Satysfakcji z Życia autorstwa Dienera. Wyniki: Analiza korelacji wykazała, samoocena, dobrostan seksualny oraz satysfakcja z życia osób z niepełnosprawnością motoryczną były ze sobą związane w sposób istotny oraz dodatni. Regresja wieloraka potwierdziła, że samoocena i seksualny dobrostan stanowiły statystycznie istotne i dodatnie predyktory subiektywnej oceny satysfakcji z życia badanych osób z niepełnosprawnością. Analiza moderacji nie wykazała, by samoocena pełniła istotną funkcje moderatora w relacji między dobrostanem seksualnym a subiektywną ocenę satysfakcji z życia badanych osób. Wnioski: Niepełnosprawność może być ograniczająca we wszystkich sferach życia, również tej seksualnej. Badacze zajmujący się funkcjonowaniem osób niepełnosprawnych powinni brać pod uwagę tę kwestię, gdyż seksualny dobrostan może istotnie kształtować satysfakcję i jakość życia osób z niepełnosprawnościami

Effect of nitrON® cetane-detergent additive to B7 fuel on energy parameters and exhaust gas composition of a 6Dg locomotive with a Caterpillar C27 engine

In order to avoid the negative effects of increasing the amount of RME in the fuel, the nitrON® package was used, containing 3 different additives: stabilizing, washing and increasing the cetane number of the fuel. The tests were carried out with the use of the Caterpillar C27 engine of the 6Dg locomotive connected to a water resistor. The hourly engine fuel consumption (FC), NOx concentration and exhaust opacity were measured for 3 points of the F test, in accordance with UIC 624. The concentration of the nitrON® additive in the test fuel was 1500 ppm (v/v). For idling, the reduction in FC value was only 1.5% (in relation to the base fuel), but for a very high engine load and nominal rotational speed, the percentage reduction in FC was as high as 5%. The reduction of NOx concentration for idling (as a result of using nitrON®) was approx. 10%, while for high engine load, the percentage reduction of NOx concentration in the exhaust gas exceeded 15%