Steroid induced osteonecrosis: An analysis of steroid dosing risk.

Osteonecrosis is a serious condition involving bone destruction that frequently requires surgical treatment to rebuild the joint. While there is an abundance of literature documenting corticosteroid related osteonecrosis, there is no consensus as to the relative risk of osteonecrosis after administration of steroids via parenteral, oral, topical, inhaled and other routes. This risk is an important prognostic indicator because identification and conservative intervention can potentially reduce morbidity associated with aggressive surgical treatment of osteonecrosis. This paper provides insight into establishing guidelines related to the risk of developing osteonecrosis as a result of corticosteroid use. Case studies, retrospective studies and prospective studies in humans on different corticosteroids and varied dosages were assessed. Most cases of osteonecrosis are secondary to systemically administered corticosteroids and/or high dose daily therapy, particularly in patients with underlying comorbidities including connective tissue diseases, hyperlipidemia, or previous trauma. Previous case reports of osteonecrosis related to inhaled or topical use of steroids are complicated by the fact that in the great majority of cases, the patients are also treated with systemic steroids prior to the development of osteonecrosis. Based on the literature, a set of recommendations regarding the risk of osteonecrosis in patients on steroids was formulated

Diagnosing B-cell acute lymphoblastic leukemia in 2 pediatric patients with recent SARS-CoV-2 infection.

COVID-19 infection is still a mystery in terms of its long-term effect on health and its consequences on hematological disorders. Prior studies including ours have shown the abnormal changes in hematopoietic cells in COVID-19 patients. In this article, we are presenting 2 cases of pediatric B-lymphoblastic leukemia (B-ALL) with a previous history of COVID-19 infection. The first case describes a 22-month-old boy presenting with lymphadenopathy, neutropenia, and anemia with concurrent COVID-19 infection without any evidence of a hematolymphoid neoplasm as per bone marrow and lymph node biopsy. However, he presented after 2 months with bone marrow biopsy confirming B-ALL. The second case is that of a 4-year-old girl presenting with B-ALL who has had asymptomatic COVID-19 infection 5 months before this current presentation. Both the cases had complete resolution of COVID-19 infection during the time of presentation with acute leukemia. There were notably 2 rare findings along the course of the patients illnesses. First, the unusual plasmacytosis in the marrow during active COVID-19 infection in the first patient and the second, is predilection of development of B-ALL following COVID-19. In both the cases the fluorescence in situ hybridization (FISH) studies showed pathologic alteration of the RUNX1 gene. Overall, there are no literature to support a causal association between acute B-ALL and COVID-19. The diagnosis of B-ALL in these patients after COVID-19 infection may be totally unrelated. However, if we consider Greaves proposed 2-hit model for childhood acute leukemia, that an infectious agent can precipitate development of B-ALL in a genetically susceptible individual. Alteration of the RUNX1 gene in both the patients, opens a door for further exploration of the second-hit hypothesis regarding an infectious agent precipitating development of B-ALL in a genetically susceptible individual

Advance in the Treatment of Pediatric Leukemia

The book gives an overview on the progress that has been made in the treatment of acute lymphoblastic leukemia (ALL), of acute and chronic myeloid leukemia (AML, CML) and of juvenile myelomonocytic leukemia (JMML). Leukemia is the most common malignant disease in children, and 80% of patients are diagnosed with ALL and 15–20% with AML, whereas CML and JMML are rather rare. Although ALL was considered an incurable disease until the early 1960s, with the availability of cytotoxic drugs and the start of clinical multicenter studies, ALL has become an almost curable disease with a survival rate exceeding 90 % in high-income countries. These impressive results have mainly been achieved by a deeper understanding of the genomic landscape of the disease and the introduction of risk stratifications based on genetic features and response to chemotherapy as determined by the presence or absence of minimal residual disease (MRD). Immunotherapies including bispecific T-cell Engagers (BiTEs), Chimeric Antigen Receptor (CAR) T cells, monoclonal antibodies and improvements in the outcome of allogeneic stem cell transplantation (HSCT) have shown impressive results in chemorefractory or relapsed patients, and it is anticipated that the cure rate can be further increased. For countries with less resources, therapies have to be adapted to increase survival as well. This book also updates on the progress made in the treatment of AML. As in ALL, risk classification based on genetic factors and response to chemotherapy is most important for therapy guidance. The book also provides updates and guidance for the treatment of CML and JMML

Studies of congenital genetic aberrations behind childhood leukemia

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, and most frequently (85%) of B-cell precursor type (BCP-ALL). Acquired chromosomal rearrangements or aneuploidies are the recurrent, often prenatal, initiators of BCP-ALL. These aberrations define distinct molecular subtypes that are associated with differences in prognosis and used to guide treatment. Initiating variants are disease driving, but secondary variants are required to drive progression to overt disease. Although constitutional predisposing variants are found in an increasing share of cases (10-18%), BCP-ALL etiology remains largely unknown. Recent studies have suggested that exposure to common infections may modulate progression of BCP-ALL. The aim of this thesis was to identify, asses and quantify congenital genetic aberrations behind childhood BCP-ALL predisposition and initiation, as well as to characterize subsequent clonal evolution and identify drivers of progression to overt disease. To this end, we performed whole genome sequencing (WGS) to identify constitutional BCP-ALL-predisposing variants. In paper I, we reported familial predisposition mediated by a constitutional t(12;14), where haploinsufficiency of the powerful transcription factor ETV6 was suggested to cause predisposition. In paper III, monozygotic twins with concordant BCP-ALL shared a constitutional, maternally inherited, novel variant in NF1, predicted to be highly damaging. As none of the carriers has any clinical sign of the cancer syndrome neurofibromatosis type 1 (NF1), we classified the variant to be of unknown significance (VUS), but speculated its possible BCP-ALL-predisposing effect. We developed a sensitive and quantitative method for backtracking BCP-ALL to pre-leukemic clones (paper II), applying chip dPCR in combination with WGS to analyze DNA from neonatal dried blood spots. In paper II, only one case of BCP-ALL, diagnosed at age 1 month, had detectable copy numbers of genomic breakpoint sequence at birth. Failed detection in the remaining six cases was suggested to be caused by technical and sample related limitations, and less frequently postnatal initiation. In paper III, WGS identified a shared somatic complex rearrangement, generating ETV6- RUNX1, in the BCP-ALLs of monozygotic twins. Detection at birth by dPCR failed, but identical breakpoint sequences confirmed its prenatal origin. Surprisingly, a shared (prenatal) deletion in UBA2 was found to precede the complex rearrangement, persisting after several years in remission. Clonal evolution of concordant BCP-ALLs was characterized in paper III, detecting shared and unique overlapping secondary putative driver variants, supporting independent although convergent clonal evolution. In paper I, 7-10 secondary putative driver variants, in genes recurrently targeted in childhood ALL, were identified in BCP-ALLs with ETV6-mediated predisposition. This further supported that secondary drivers are required for progression, although phylogenetics of somatic events in ETV6-predisposed cases remains to be delineated. In paper IV, we assessed a Swedish population-based cohort of 1380 BCP-ALL cases and used GARIMAX to demonstrate informative seasonal variation in onset and interpreted peak onset to fall in August. Four explanatory models, related to exposure to common infections as a driver of final progression to overt disease, were suggested. The likelihood of each model depends on still unknown induction time of childhood BCP- ALL. Together, these studies add to our understanding of; congenital susceptibility to BCP-ALL through constitutional predisposing variants and prenatally initiated pre-leukemic clones, progression to overt disease through somatic clonal evolution and the genetic and environmental drivers of this process

Risk factors associated with paediatric leukemia – a preliminary study amongst parents

Background: Acute lymphoblastic leukemia (ALL) is the most common leukemia seen among pediatric patients. Exposure to agents such as pesticides, tobacco smoke, solvents, and air pollution associated with traffic, factories, and incinerators is consistently associated with an increased risk of developing childhood leukemia. The purpose of this article is to attempt to assess the knowledge of parents of oncology patients about possible risk factors for the development of ALL acute lymphoblastic leukemia and the need for educational campaigns to increase cancer awareness in the community. Material and methods: For the study, the authors created a structured questionnaire that included 15 questions. The printed questionnaire was then distributed to parents staying with their children in the pediatric oncology and hematology department and the hematology-oncology outpatient clinic at 2 clinical hospitals in Poland. The survey was conducted from February to May 2023. Results: The study group was formed by 256 people. 13% of respondents believe that breastfeeding increases a child's risk of leukemia. One in three questioned pointed to vaccinations as a possible trigger for cancer. The majority of respondents consider care facilities such as the nursery as exposure to the development of leukemia. The vast majority of respondents are dissatisfied with their knowledge of proliferative diseases. Conclusions: The overall level of parents' knowledge of leukemia risk factors is inadequate. A large percentage of respondents indicate vaccination as a risk factor for the development of ALL There is a need for educational campaigns on childhood cancer. There is a need to verify the sources of medical knowledge used by patients, especially on the Internet

IL-6 і TGF-β як маркери пошкодження аерогематичного бар’єру у дітей з гострою лімфобластною лейкемією: клінічні та прогностичні аспекти

Background. Damage markers of blood-air barrier are important for studding pathological process in lungs in children with acute lymphoblastic leukemia (ALL). Purpose is to analyses pulmonary complications and to assess IL-6 and TGF-β levels in the exhaled breath condensate (EBC) in children with ALL and its prognostic value. Materials and Methods. 40 children with ALL aged 6–17 years were examined. 1st group included newly diagnosed ALL (n = 18). 2nd group involved ALL survivors who had completed course of ALL IC BFM 2009 protocols (n = 22). The control group consisted of 15 healthy children. The levels of IL-6 and TGF- β in the EBC were analyzed by ELISA. Results and discussion. Pulmonary complications presented in 82.5% of children with ALL during chemotherapy and in 15.8% of ALL survivors. IL-6 and TGF-β levels in EBC were significantly higher in both ALL groups than control: IL-6 p1-C = 0,000001; p2-C = 0,000000; TGF-β p1-C = 0.000014; p2-C = 0.009364. 1st group had higher levels of IL-6 and TGF-β in the EBC than 2nd group: IL-6 p1-2 = 0,000000; TGF-β p1-2 = 0.000141. There was a positive correlation between IL-6 and TGF-β levels (r = 0.681176, p = 0.000001). According to ROC analysis, IL-6 level in EBC collected during Protocol 1 > 47.64 pg/ml can be prognostic for pulmonary complications during chemotherapy (AUC 0.875; Sensitivity 75.0%; Specificity 100,0%). Level of IL-6 > 49.96 pg/ml can predict pneumonia during chemotherapy (AUC 0,883; Sensitivity 100.00%; Specificity 81.82%). IL-6 level after the total course of chemotherapy > 23.64 pg/ml can predict pulmonary complications in ALL survivors (AUC 0.819; Sensitivity 75.00%; Specificity 81.82%). TGF-β level in EBC after the completion of chemotherapy > 19.93 pg/ml can be prognostic for pulmonary complications in ALL survivors (AUC 0.896; Sensitivity 100.00%; Specificity 77.78%). Conclusions. IL-6 and TGF-β levels in EBC can be prognostic for pulmonary complications in children with ALL.Актуальність. Вивчення маркерів пошкодження аерогематичного бар’єру має важливе значення для розуміння патологічного процесу в легенях дітей з гострою лімфобластною лейкемією (ГЛЛ). Мета роботи. Проаналізувати легеневі ускладнення та оцінити рівень IL-6 і TGF-β у конденсаті повітря, що видихається (КВП) та його прогностичне значення у дітей з ГЛЛ. Матеріали та методи. Обстежено 40 дітей з ГЛЛ віком 6–17 років. Перша група включала дітей з вперше діагностованою ГЛЛ (n = 18). Друга група включала дітей у ремісії, які пройшли повний курс протоколів ALL IC BFM 2009 (n = 22). Контрольну групу склали 15 здорових дітей. Рівні IL-6 і TGF-β в КВП аналізували методом ELISA. Результати та їх обговорення. Легеневі ускладнення спостерігалися у 82,5% дітей з ГЛЛ під час хіміотерапії та у 15,8% дітей у довгостроковій ремісії. Рівні IL-6 та TGF-β у КВП були значно вищими в обох групах з ГЛЛ, порівняно з контрольною групою: IL-6 p1-C = 0,000001; p2-C = 0,000000; TGF-β p1-C = 0,000014; p2-C = 0,009364. 1-ша група мала достовірно вищі рівні IL-6 та TGF-β в EBC, ніж 2-га група: IL-6 p1-2 = 0,000000; TGF-β p1-2 = 0,000141. Виявлена позитивна кореляція між рівнями IL-6 і TGF-β (r = 0,681176, p = 0,000001). Відповідно до ROC аналізу, рівень IL-6 у КВП, зібраний під час протоколу 1 > 47,64 пг/мл, може бути прогностичним для гострих легеневих ускладнень під час протоколів хіміотерапії (AUC 0,875; чутливість 75,0%; специфічність 100,0%). Рівень IL-6 > 49,96 пг/мл може прогнозувати пневмонію під час хіміотерапії (AUC 0,883; чутливість 100,0%; специфічність 81,82%). Рівень IL-6 після завершення курсу хіміотерапії > 23,64 пг/мл може прогнозувати легеневі ускладнення у дітей у довготривалій ремісії ГЛЛ (AUC 0,819; чутливість 75,00%; специфічність 81,82%). Рівень TGF-β у КВП після завершення протоколів хіміотерапії > 19,93 пг/мл може бути прогностичним для легеневих ускладнень у довготривалій ремісії ГЛЛ (AUC 0,896; чутливість 100,0%; специфічність 77,78%). Висновки. Рівні IL-6 і TGF-β у КВП можуть бути прогностичними для визначення розвитку легеневих ускладнень у дітей з ГЛЛ

International Conference on Pharmaceutical and Natural Sciences

UBT Annual International Conference is the 9th international interdisciplinary peer reviewed conference which publishes works of the scientists as well as practitioners in the area where UBT is active in Education, Research and Development. The UBT aims to implement an integrated strategy to establish itself as an internationally competitive, research-intensive university, committed to the transfer of knowledge and the provision of a world-class education to the most talented students from all background. The main perspective of the conference is to connect the scientists and practitioners from different disciplines in the same place and make them be aware of the recent advancements in different research fields, and provide them with a unique forum to share their experiences. It is also the place to support the new academic staff for doing research and publish their work in international standard level. This conference consists of sub conferences in different fields like: Art and Digital Media Agriculture, Food Science and Technology Architecture and Spatial Planning Civil Engineering, Infrastructure and Environment Computer Science and Communication Engineering Dental Sciences Education and Development Energy Efficiency Engineering Integrated Design Information Systems and Security Journalism, Media and Communication Law Language and Culture Management, Business and Economics Modern Music, Digital Production and Management Medicine and Nursing Mechatronics, System Engineering and Robotics Pharmaceutical and Natural Sciences Political Science Psychology Sport, Health and Society Security Studies This conference is the major scientific event of the UBT. It is organizing annually and always in cooperation with the partner universities from the region and Europe. We have to thank all Authors, partners, sponsors and also the conference organizing team making this event a real international scientific event. Edmond Hajrizi, President of UBT UBT – Higher Education Institutio

Endocan in Acute Leukemia: Current knowledge and future perspectives

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Endocan is a soluble dermatan sulfate proteoglycan expressed by endothelial cells and detected in serum/plasma. Its expression is increased in tumors/tumor vessels in several human malignancies, and high expression (high serum/plasma levels or tumor levels) has an adverse prognostic impact in several malignancies. The p14 endocan degradation product can also be detected in serum/plasma, but previous clinical studies as well as previously unpublished results presented in this review suggest that endocan and p14 endocan fragment levels reflect different biological characteristics, and the endocan levels seem to reflect the disease heterogeneity in acute leukemia better than the p14 fragment levels. Furthermore, decreased systemic endocan levels in previously immunocompetent sepsis patients are associated with later severe respiratory complications, but it is not known whether this is true also for immunocompromised acute leukemia patients. Finally, endocan is associated with increased early nonrelapse mortality in (acute leukemia) patients receiving allogeneic stem cell transplantation, and this adverse prognostic impact seems to be independent of the adverse impact of excessive fluid overload. Systemic endocan levels may also become important to predict cytokine release syndrome after immunotherapy/haploidentical transplantation, and in the long-term follow-up of acute leukemia survivors with regard to cardiovascular risk. Therapeutic targeting of endocan is now possible, and the possible role of endocan in acute leukemia should be further investigated to clarify whether the therapeutic strategy should also be considered.publishedVersio

Endocan in Acute Leukemia: Current Knowledge and Future Perspectives

Endocan is a soluble dermatan sulfate proteoglycan expressed by endothelial cells and detected in serum/plasma. Its expression is increased in tumors/tumor vessels in several human malignancies, and high expression (high serum/plasma levels or tumor levels) has an adverse prognostic impact in several malignancies. The p14 endocan degradation product can also be detected in serum/plasma, but previous clinical studies as well as previously unpublished results presented in this review suggest that endocan and p14 endocan fragment levels reflect different biological characteristics, and the endocan levels seem to reflect the disease heterogeneity in acute leukemia better than the p14 fragment levels. Furthermore, decreased systemic endocan levels in previously immunocompetent sepsis patients are associated with later severe respiratory complications, but it is not known whether this is true also for immunocompromised acute leukemia patients. Finally, endocan is associated with increased early nonrelapse mortality in (acute leukemia) patients receiving allogeneic stem cell transplantation, and this adverse prognostic impact seems to be independent of the adverse impact of excessive fluid overload. Systemic endocan levels may also become important to predict cytokine release syndrome after immunotherapy/haploidentical transplantation, and in the long-term follow-up of acute leukemia survivors with regard to cardiovascular risk. Therapeutic targeting of endocan is now possible, and the possible role of endocan in acute leukemia should be further investigated to clarify whether the therapeutic strategy should also be considered.publishedVersio