Blood donors’ positivity for transfusion-transmissible infections: the Serbian Military Medical Academy experience

Background

Members of armed forces worldwide are considered to be very susceptible to sexually transmitted infections, thus falling into a high-risk group of blood donors regarding transfusion-transmissible infections. In the Serbian Military Medical Academy a significant number (44% for the period 2005–2013) of blood donations were from members of the Serbian Army. The aim of this study was to determine the significance of military blood donors for the safety of blood transfusion.

Material and methods

Between January 2005 and December 2013, a total of 155,479 blood donations were tested for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and syphilis using serological assays (enzyme immunoassays, chemiluminescent microparticle immunoassay and western blot) and molecular testing (polymerase chain reaction analysis).

Results

The percentage of blood donations positive for transfusion-transmissible infections in the estimated period was 0.38%, and the percentage of HBV, HCV, HIV and syphilis positive blood donations was 0.20%, 0.12%, 0.005% and 0.06%, respectively. During that period, the percentage of all transfusion-transmissible infections, and in particular of HBV and HCV, declined significantly. In contrast, the percentage of HIV and syphilis positive blood donations remained unchanged. Higher rates of positivity for transfusion-transmissible infections in blood donations from members of the Serbian Army were not found, especially after mandatory military service was abolished in 2009.

Discussion

The reported rate of positivity for transfusion-transmissible infections in blood donations from the Military Medical Academy was considered low. This information is of great significance for further implementation of public health measures.     

Emdogain in regenerative periodontal therapy. A review of the literature

The goal of regenerative periodontal therapy is the reconstitution of the lost periodontal structures (i.e. the new formation of root cementum, periodontal ligament and alveolar bone). Results from basic research have pointed to the important role of the enamel matrix protein derivative (EMD) in the periodontal wound healing. Histological results from animal and human studies have shown that treatment with EMD promotes periodontal regeneration. Moreover, clinical studies have indicated that treatment with EMD positively influences periodontal wound healing in humans. The goal of the current overview is to present, based on the existing evidence, the clinical indications for regenerative therapy with EMD. Surgical periodontal treatment of deep intrabony defects with EMD promotes periodontal regeneration. The application of EMD in the context of non-surgical periodontal therapy has failed to result in periodontal regeneration. Surgical periodontal therapy of deep intrabony defects with EMD may lead to significantly higher improvements of the clinical parameters than open flap debridement alone. The results obtained following treatment with EMD are comparable to those following treatment with GTR and can be maintained over a longer period. Treatment of intrabony defects with a combination of EMD + GTR does not seem to additionally improve the results compared to treatment with EMD alone or GTR alone. The combination of EMD and some types of bone grafts/bone substitutes may result in certain improvements in the soft and hard tissue parameters compared to treatment with EMD alone. Treatment of recession-type defects with coronally repositioned flaps and EMD may promote formation of cementum, periodontal ligament and bone, and may significantly increase the width of the keratinized tissue. Application of EMD seems to provide better long-term results than coronally repositioned flaps alone. Application of EMD may enhance periodontal regeneration in mandibular Class II furcations. The clinical results are comparable to those obtained following GTR.     

Isolated and combined dystonia syndromes – an update on new genes and their phenotypes

Recent consensus on the definition, phenomenology and classification of dystonia centres around phenomenology and guides our diagnostic approach for the heterogeneous group of dystonias. Current terminology classifies conditions where dystonia is the sole motor feature (apart from tremor) as ‘isolated dystonia’, while ‘combined dystonia’ refers to dystonias with other accompanying movement disorders. This review highlights recent advances in the genetics of some isolated and combined dystonic syndromes. Some genes, such as ANO3, GNAL and CIZ1, have been discovered for isolated dystonia, but they are probably not a common cause of classic cervical dystonia. Conversely, the phenotype associated with TUBB4A mutations expanded from that of isolated dystonia to a syndrome of hypomyelination with atrophy of the basal ganglia and cerebellum (H‐ABC syndrome). Similarly, ATP1A3 mutations cause a wide phenotypic spectrum ranging from rapid‐onset dystonia‐parkinsonism to alternating hemiplegia of childhood. Other entities entailing dystonia‐parkinsonism include dopamine transporter deficiency syndrome (SLC63 mutations); dopa‐responsive dystonias; young‐onset parkinsonism (PARKIN, PINK1 and DJ‐1 mutations); PRKRA mutations; and X‐linked TAF1 mutations, which rarely can also manifest in women. Clinical and genetic heterogeneity also characterizes myoclonus‐dystonia, which includes not only the classical phenotype associated with epsilon‐sarcoglycan mutations but rarely also presentation of ANO3 gene mutations, TITF1 gene mutations typically underlying benign hereditary chorea, and some dopamine synthesis pathway conditions due to GCH1 and TH mutations. Thus, new genes are being recognized for isolated dystonia, and the phenotype of known genes is broadening and now involves different combined dystonia syndromes.     

The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4⁺ and CD8⁺ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no “antigenic competition” in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies.     

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.     

After treat-to-target: can a targeted ultrasound initiative improve RA outcomes?

For patients with rheumatoid arthritis (RA), remission can be achieved with tight control of inflammation and early use of disease modifying agents. The importance of remission as an outcome has been recently highlighted by European League Against Rheumatism recommendations. However, remission when defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who have recently formed a research network--the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted ultrasound in RA.