Early mixed chimerism‐based preemptive immunotherapy in children undergoing allogeneic hematopoietic stem cell transplantation for acute leukemia

This retrospective analysis comprises 10‐year experience with early posttransplant mixed chimerism‐based preemptive intervention. Out of 104 patients, 51 received preemptive immunotherapy. Their outcomes were similar to patients achieving full donor chimerism spontaneously. Among patients receiving intervention, 5‐year event‐free survival was identical in patients with and without pretransplant residual disease, respectively (68% [95% confidence interval (CI) 38–98%] vs. 69% [95% CI 54–85%] log–rank = 0.4). In patients who received preemptive immunotherapy, chimerism status and residual disease prior to transplant were no longer predictors of poor outcome; however, 41% of the patients with residual disease prior to transplant relapsed early and did not benefit from this strategy.     

The impact of primary packaging on the quality of parenteral products

The unique approach in manufacturing of pharmaceutical dosage forms of active substances known to be unstable in aqueous solution is the introduction of lyophilization process. Nevertheless, these products must be reconstituted using the diluent from a separate container before application. The possible solution for this problem is the application of dual chamber vials comprising the freeze-dried product in a lower compartment of the vial and the solution for reconstitution in the upper chamber. The main issue in development of such product is the choice of contact packaging (rubber closures, glass vials and the container closure system as a whole). The most important parameter used for evaluation of the influence of contact material on product quality was the pH value. The results have shown that the type of vials (moulded or tubular glass) has no impact on pH shift of the solution for reconstitution (tested solution-TS), while significant differences in pH value of the TS were observed depending on the rubber closures formulation used (with some formulations, the pH shift during the test was 6.5-9.14). Benzyl alcohol assay during the tests remained unchanged. Integrity tests of the container closure system (CCS) have demonstrated the adequacy of the selected packaging system. The quality of the CCS of choice was confirmed in the course of stability studies, only parameters directly influenced by CCS being presented in this work: loss on drying and pH value. On the basis of these results, no changes in loss on drying were connected to CCS, and the pH value of the reconstituted solution remains unchanged in samples tested both ex-tempore and after in-use period of 48 h.     

Assessment of Heavy Metal Contamination and Calculation of Its Pollution Index for Uglješnica River,Serbia

The aim of the study was to assess the water pollution in terms of total content of heavy metals by parameter called Heavy metal pollution index (HPI). The water samples were collected from four different locations along the course of the river during spring and the autumn seasons. The concentrations of lead (Pb), cadmium (Cd), iron (Fe), zinc (Zn), manganese (Mn), copper (Cu), arsenic (As) and mercury (Hg) were determined using atomic absorption spectroscopy. The data were used to evaluate HPI of the river water. The mean value of HPI was 67.487 for the spring season, and 80.676 for the autumn season. The average for both seasons and all sampling sites is 74.082. The maximum value of 112.722 found at one sampling site is above the critical index limit of 100. Also, from the values of mean HPI for each sampling site could be concluded that the pollution load at sampling site-4 is the most significant (HPI 89.575).     

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy‐four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01–1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08–1.98; p = 0.015). Registration on trials was not associated with Gram‐negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML.     

Structure-Activity Relationship Study of Novel Peptoids That Mimic the Structure of Antimicrobial Peptides

The constant emergence of new bacterial strains that resist the effectiveness of marketed antimicrobials has led to an urgent demand for and intensive research on new classes of compounds to combat bacterial infections. Antimicrobial peptoids comprise one group of potential candidates for antimicrobial drug development. The present study highlights a library of 22 cationic amphipathic peptoids designed to target bacteria. All the peptoids share an overall net charge of +4 and are 8 to 9 residues long; however, the hydrophobicity and charge distribution along the abiotic backbone varied, thus allowing an examination of the structure-activity relationship within the library. In addition, the toxicity profiles of all peptoids were assessed in human red blood cells (hRBCs) and HeLa cells, revealing the low toxicity exerted by the majority of the peptoids. The structural optimization also identified two peptoid candidates, 3 and 4, with high selectivity ratios of 4 to 32 and 8 to 64, respectively, and a concentration-dependent bactericidal mode of action against Gram-negative Escherichia coli.     

Switching to BCL-6 Negativity in Relapsed Diffuse Large B Cell Lymphoma Correlated with More Aggressive Disease Course

Diffuse large B-cell lymphoma (DLBCL) is the most frequent, complex and heterogeneous lymphoma of adulthood. Heterogeneity is expressed at clinical, genetic, and molecular levels. It is known that BCL-6 expression is a favorable prognostic factor in DLBCL. However, the underlying mechanisms of BCL-6 expression in DLBCL relapse are not yet elucidated. Here, we present so far undescribed clinical phenomenon of switching BCL-6⁺ protein expression into BCL-6⁻ expression in 19 of 41 relapsed DLBCL patients. The switch in relapsed DLBCL was associated with more aggressive clinical course of the disease. Bone marrow infiltration and high IPI risk were more often present in BCL-6⁻ patients. Significantly increased biochemical parameters, such as LDH, beta-2 macroglobulin, CRP, and ferritin have been found, as well as significantly decreased serum Fe, TIBC, and hemoglobin. A Ki-67 proliferation marker was considerably high in relapsed DLBCL, but without significant differences between BCL-6⁺ and BCL-6⁻ groups of patients. Thus, switching of the positive into negative BCL-6 expression during DLBCL relapse could be used as a prognostic factor and a valuable criterion for treatment decision.     

Mortality of Roma population in Serbia, 2002-2005

Aim

To describe and compare mortality and population changes in the Roma and non-Roma population in Serbia in 2002 and 2005.

Methods

The number of cases of death were obtained from the 2002 and 2005 Mortality Database and population data from the Population Census 2002. Standardized sex specific rates of non-traumatic and traumatic mortality in 2002 and 2005 were calculated in relation to the European standard population. We presented population pyramid and aging index for both populations in 2002 and compared sex specific standardized traumatic and non-traumatic mortality rates and the average age of death for 2002 and 2005. The causes of death were coded according to the 10th revision of the International Classification of Diseases (ICD-10) groups, and the proportional mortalities in the year 2002 and 2005 were compared between the Roma and non-Roma population using χ² test.

Results

Standardized mortality rates were higher in the Roma than in the general population. Non-traumatic mortality rate in Roma men in 2002 was 18.2 per 1000 and in slightly decreased to 18.0 per 1000 in 2005; it was significantly higher than in non-Roma men in both years (11.9 per 1000 in 2002 and 12.5 per 1000 in 2005; P<0.001). Standardized non-traumatic mortality rate in Roma women decreased significantly from 16.78 per 1000 in 2002 to 14.89 per 1000 in 2005 (P=0.014), but it was still significantly higher than in non-Roma women (8.46 per 1000 in 2002 and 8.84 per 1000 in 2005; P<0.001). Morbidity structure indicated that the most common causes of death in the Roma population were cardiovascular diseases, neoplasms, and respiratory system diseases. In relation to the general population respiratory system diseases were denoted as main causes of deaths in significantly higher percent (6% vs 3% in 2002 and 7% vs 4% in 2005; P<0.001) and cardiovascular diseases in significantly lower percent (44%:55% in 2002 and 46%:57%; P<0.001).

Conclusions

Our data show that mortality rates in the Roma population are significantly higher than in the general population, and morbidity structure of the most common causes of death significantly different from that of general population.According to the most recent population census in the Serbia from 2002, 108 193 or 1.44% residents declared themselves as Romani. The Roma population is among the most imperiled and potentially most vulnerable groups. Living Standards Measurement Survey (LSMS) conducted in Serbia in 2002-2003 indicated significant differences in living conditions between the Roma and non-Roma population (1). The prevalence of poverty, defined as an average total consumption below the poverty line of 57 euros per month/consumption unit, in the Roma population was as high as 64.4%, which is 6.1 times more frequent than in the general population (10.5%) (1). Extremely low level of education and very high level of unemployment characterize the social status of the Romani people. Almost two thirds (62%) of the Roma older than 15 years did not finish primary school, as opposed to 19% of the general population (1). The unemployment rate is also high, reaching 45%, while in the rest of the Serbian population it amounts to 9% (1). Such findings are not unexpected since these characteristics are highly associated with poverty (1).Although the range of vaccination coverage in Serbian general population is 98%-100%, many Roma children are not included in vaccination programs (2). Twenty nine percent of Roma children aged 18-29 months do not even have vaccination cards. Data regarding the education of Roma children are also discouraging: 62% of them attended pre-school programs one year prior to the first grade, as opposed to 89% children in the general population. Also, the vast majority (98%) of children of primary school age in general population attends school, while the attendance rate among Roma children is significantly lower (74%). The difference between the proportions of Roma children and children in general population who attend secondary schools is even more drastic (only 10% vs 85%).During the last decade, several studies dealing with diverse problems of the Roma population have been conducted in South-Eastern Europe (3-10). Compared with the general populations in Eastern and Central Europe, life expectancy of the Roma population is 10-year shorter because of poor living conditions and poverty (11). A study conducted in the Czechoslovakia in 1989 compared census data and pointed out that life expectancy of the Roma men and women were 12.1 and 14.4 years, respectively, shorter than in the general population (12).The aim of this study was to describe and compare mortality and population changes in the Roma and non-Roma population in Serbia in 2002 and 2005. We present population pyramid and aging index for both populations for the year 2002 and compared sex specific standardized traumatic and non-traumatic mortality rates and the average age of death for 2002 and 2005.     

Patients with Acute Lacunar Infarction Have Benefit from Intravenous Thrombolysis

Introduction: Usefulness of intravenous thrombolysis in patients with acute lacunar cerebral infarction is questionable. The aim of this study was to evaluate the efficacy and safety of intravenous thrombolysis in patients with lacunar infarction in comparison with patients with nonlacunar infarction as well as with patients with lacunar infarction who were not treated with intravenous thrombolysis. Materials and methods: In the first part of the study, among patients with acute ischemic stroke treated with intravenous thrombolysis, characteristics and outcomes of 46 patients with lacunar and 221 patients with nonlacunar infarction were compared. In the second part, 46 patients with lacunar infarction treated with intravenous thrombolysis were compared with 45 lacunar infarction patients who were not treated with intravenous thrombolysis. Results: Patients with lacunar infarction had a lower National Institutes of Health Stroke Scale score (9.2 versus 13.9, P < .001), a greater Alberta Stroke Program Early computed tomography (CT) score (9.7 versus 9.2, P?=?.002), a lower prevalence of atrial fibrillation (6.5% versus 41.2%, P < .001), and significantly more frequently an excellent outcome after 3 months (76.1% versus 36.2%, P < .001) compared with patients with nonlacunar infarction. Among patients with lacunar infarction, an excellent outcome at discharge was significantly more frequent in the intravenous thrombolysis group (41.3% versus 15.6%, P?=?.01), and the length of hospitalization was significantly shorter (9.5 days versus 14.3 days, P?=?.002). There was no hemorrhagic transformation among patients with lacunar infarction treated with intravenous thrombolysis. Conclusion: Intravenous thrombolysis has proven to be effective and safe in patients with lacunar infarction and should always be applied if there are no absolute contraindications.