Unrelated Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia: Experience at a Single Institution

We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients developed grade II-IV acute graft-versus-host disease (GVHD) and 8 developed extensive chronic GVHD. With median follow-up of 39.1 months, event free survival and overall survival were 60.4% and 67.5%, respectively, at 5 yr. Events included relapse in 10 and treatment-related mortality (TRM) in 10. The causes of TRM included sepsis in 4, GVHD in 4 (1 acute GVHD and 3 chronic GVHD), veno-occlusive disease in 1 and fulminant hepatitis in 1. Patients transplanted with CB had event free survival of 57.1%, comparable to 63.2% for those transplanted with other than CB. In conclusion, HCT with unrelated donors is effective treatment modality for children with acute leukemia. In children with acute leukemia candidate for HCT but lack suitable sibling donor, unrelated HCT may be a possible treatment option at the adequate time of their disease

Changes of Body Weight and Inflammatory Markers after 12-Week Intervention Trial: Results of a Double-Blind, Placebo-Control Pilot Study

∙ The authors have no financial conflicts of interest. Purpose: Low grade inflammation is a well-known characteristic in obese subjects. We investigated body weight changes and inflammatory markers after 12week intervention trial. Materials and Methods: Twenty-six obese subjects were enrolled and 19 (13 men and 6 women) completed the study. Sibutramine is an FDA-approved drug for body weight control; therefore, we chose this drug as the standard treatment medication in this study. Patients were randomly allocated to receive an anti-inflammatory agent (Diacerein treatment group; n = 12) or placebo (n = 7) for 12 weeks. Anthropometry, body proportion by dual-energy X-ray absorptiometry, and metabolic parameters at the beginning and end of study were measured and compared. Results: The treatment group had a tendency towards more reduction in anthropometry as compared to the placebo group, in body weight reduction (- 7.0 kg vs.- 4.6 kg), body mass index (- 2.51 kg/m 2 vs.- 1.59 kg/m 2), and waist circumference (- 7.3 cm vs.- 4.4 cm). These reductions were not statistically significant

Higher levels of serum triglyceride and dietary carbohydrate intake are associated with smaller LDL particle size in healthy Korean women

The aim of this study was to investigate the influencing factors that characterize low density lipoprotein (LDL) phenotype and the levels of LDL particle size in healthy Korean women. In 57 healthy Korean women (mean age, 57.4 ± 13.1 yrs), anthropometric and biochemical parameters such as lipid profiles and LDL particle size were measured. Dietary intake was estimated by a developed semi-quantitative food frequency questionnaire. The study subjects were divided into two groups: LDL phenotype A (mean size: 269.7Å, n = 44) and LDL phenotype B (mean size: 248.2Å, n = 13). Basic characteristics were not significantly different between the two groups. The phenotype B group had a higher body mass index, higher serum levels of triglyceride, total-cholesterol, LDL-cholesterol, apolipoprotein (apo)B, and apoCIII but lower levels of high density lipoprotein (HDL)-cholesterol and LDL particle size than those of the phenotype A group. LDL particle size was negatively correlated with serum levels of triglyceride (r = -0.732, P < 0.001), total-cholesterol, apoB, and apoCIII, as well as carbohydrate intake (%En) and positively correlated with serum levels of HDL-cholesterol and ApoA1 and fat intake (%En). A stepwise multiple linear regression analysis revealed that carbohydrate intake (%En) and serum triglyceride levels were the primary factors influencing LDL particle size (P < 0.001, R2 = 0.577). This result confirmed that LDL particle size was closely correlated with circulating triglycerides and demonstrated that particle size is significantly associated with dietary carbohydrate in Korean women

Novi kopolimerni zwitterionski matriksi za polagano oslobađanje verapamil hidroklorida

Stable co-polymer [vinyl acetate-co-3-dimethyl(methacryloyloxyethyl)ammonium propane sulfоnate, p(VA-co-DMAPS)] latex of different compositions has been synthesized for the first time by emulsifier-free emulsion copolymerization. The unusual “overshooting” behavior of the co-polymer tablets has been explained by the formation of specific clusters from the opposite oriented dipoles zwitterionic species. The change of their concentration with the DMAPS unit fraction (mDMAPS), pH and ionic strength has been considered responsible for the differences observed in the swelling kinetics. The results obtained prove that mDMAPS and ionic strength could be used to control the swelling degree of the p(VA-co-DMAPS) matrices. In this way, p(VA-co-DMAPS) matrices could be effectively used to control the sustained release of drugs with basic properties like verapamil hydrochloride from model tablets.Metodom emulzijske polimerizacije sintetiziran je novi stabilni kopolimer [vinil acetat-ko-3-dimetil(metakriloiloksietill)amonijev propan sulfоnat, p(VA-co-DMAPS)] lateks promjenjivog sastava. Neobično “overshooting” ponašanje tableta pripravljenih iz tog kopolimera objašnjava se stvaranjem specifičnih klastera suprotno rijentiranih dipola zwitterionskih specija. Proučavan je utjecaj udjela DMAPS jedinica (mDMAPS), pH i ionske jakosti na kinetiku bubrenja. Dobiveni rezultati dokazuju da se promjenom mDMAPS i ionske jakosti može kontrolirati stupanj bubrenja p(VA-co-DMAPS) matriksa i oslobađanje verapamil hidroklorida iz tableta pa se ti matriksi mogu upotrijebiti za polagano oslobađanje bazičnih lijekova srodnih verapamilu

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Approved and experimental small-molecule oncology kinase inhibitor drugs: a mid-2016 overview

Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult—even for those working in the field—easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation. The purpose of this review is thus to provide an overview of the biomedical rationales for the kinases being targeted on the one hand, and the design principles, as well as chemical, pharmacological, pharmaceutical, and toxicological kinase inhibitor properties, on the other hand. Two issues that are especially important in kinase inhibitor research, target selectivity and drug resistance, as well as the underlying structural concepts, are discussed in general terms and in the context of relevant kinases and their inhibitors