Short term effects of interceptive expansion treatment: a prospective study.

OBJECTIVES: This prospective cohort study investigated the short term effects of interceptive orthodontic treatment with a removable expansion plate, evaluating the changes in occlusion in all its dimensions: transversal, sagittal and vertical. SUBJECTS AND METHODS: A total of 226 patients treated with a removable expansion plate (slow maxillary expansion, SME) by orthodontic residents at the Department of Orthodontics, University Hospitals Leuven, Belgium were included. The patients had a mean age of 8.5 years at the start of the treatment. The mean treatment time was 6.9 months. Transversal measurements (intercanine and intermolar width) and occlusal characteristics (molar occlusion, overjet, overbite and functional shift) were collected before (T0) and after active treatment (T1). Statistical analysis was performed using the Wilcoxon signed rank test, Sign test and McNemar test for assessing changes between T0 and T1. Linear models were used to assess the associations between patient factors and the amount of expansion. RESULTS: A significant increase in transversal width at different occlusal landmarks was found. Correction of unilateral, bilateral and frontal crossbites was successful in 99.0%, 95.2% and 93.6% of the cases respectively. Changes in sagittal molar occlusion were significant: 64.9% (right side) and 62.6% (left side) remained stable, 28.4% (right) and 29.3% (left) improved and 6.7% (right) and 8.1% (left) deteriorated. Overbite changes were found to be statistically significant, though clinically irrelevant. Overjet changes were non-significant. CONCLUSIONS: A removable expansion plate is successful in improving the transversal dental dimensions of the maxilla. Statistically significant sagittal effects on molar occlusion were found. Long-term follow-up is needed to evaluate the long-term stability of this treatment.

Medical costs of treatment and survival of patients with acute myeloid leukemia in Belgium.

The advent of new cell-based immunotherapies for leukemia offers treatment possibilities for certain leukemia subgroups. The wider acceptability of these new technologies in clinical practice will depend on its impact on survival and costs. Due to the small patient groups who have received it, these aspects have remained understudied. This non-randomized single-center study evaluated medical costs and survival for acute myeloid leukemia between 2005 and 2010 in 50 patients: patients treated with induction and consolidation chemotherapy (ICT) alone; patients treated with ICT plus allogeneic hematopoietic stem cell transplantation (HCT), which is the current preferred post-remission therapy in patients with intermediate- and poor-risk AML with few co-morbidities, and patients treated with ICT plus immunotherapy using autologous dendritic cells (DC) engineered to express the Wilms' tumor protein (WT1). Total costs including post- consolidation costs on medical care at the hematology ward and outpatient clinic, pharmaceutical prescriptions, intensive care ward, laboratory tests and medical imaging were analyzed. Survival was markedly better in HCT and DC. HCT and DC were more costly than ICT. The median total costs for HCT and DC were similar. These results need to be confirmed to enable more thorough cost-effectiveness analyses, based on observations from multicenter, randomized clinical trials and preferably using quality-adjusted life-years as an outcome measure.

Usability of dexmedetomidine for deep sedation in infants and small children with respiratory morbidities.

BACKGROUND: Children with respiratory morbidities are at increased risk of developing adverse respiratory events while undergoing deep sedation. Dexmedetomidine possesses sedative properties with minimal respiratory depression. This report aimed to determine the usability of dexmedetomidine in children with significant respiratory morbidities who require deep sedation. METHODS: Medical records of children with ASA classification III who had at least three characteristics of respiratory morbidities and who received dexmedetomidine sedation for magnetic resonance imaging (MRI) between January 2014 and May 2015 were retrospectively reviewed. Dexmedetomidine was administered as a bolus of 1 µg/kg over 10 min followed by 1 µg/kg/h infusion. If necessary, an additional bolus dose was given and the infusion rate was increased to 2 µg/kg/h. Respiratory morbidities, haemodynamic parameters, total dexmedetomidine dose, adverse cardiorespiratory events and sedation characteristics were analysed. RESULTS: Nineteen out of 642 children who underwent MRI were eligible for evaluation. Seventeen children (89%) had at least four characteristics of respiratory morbidities. The median [IQR] age was 9 months [3.5-14]. All patients completed MRI scans while breathing spontaneously via the native airway. No episodes of adverse respiratory events or haemodynamic instability were observed. Children who were administered a lower dexmedetomidine dose and had a shorter sedation time were more likely to be younger than 1 year of age. CONCLUSION: These data demonstrate that dexmedetomidine deep sedation was well-tolerated in children with significant respiratory morbidities. Moreover, children younger than 1 year of age were administered lower dexmedetomidine dose than children older than 1 year of age for the same sedation level. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02555605.

Burkitt Lymphoma Mimicking an Acute Appendicitis in a 17 Years Old Boy: a Case Report.

Burkitt lymphoma belongs to the B cell non-Hodgkin tumors and is known as the fastest growing human tumor. It is mostly seen in children and young adults. Typically for this type of lymphoma is the chromosomal translocation that leads to a deregulated expression of the c-myc oncogene. Our case report describes a 17 year old patient who presents with atypical right lower quadrant pain. He underwent an explorative laparoscopy and a Burkitt lymphoma was discovered. Subsequently several imaging studies were performed to stage the disease. Intensive systemic chemotherapy is the choice of treatment. Surgery can have a role in early stages and acute complications of the tumor but frequently the role of surgery is restricted to histological biopsy.

Plerixafor prescription modalities in autologous haematopoietic stem cell mobilization in Belgium.

OBJECTIVES: The efficacy and safety of plerixafor, an antagonist of the CXCR4 receptor, in combination with G-CSF has been demonstrated in patients suffering from Iymphoma and multiple myeloma (MM) eligible for autologous haematopoietic stem cell collection. However, different reimbursement criteria have been applied in different countries to select patients eligible for treatment with plerixafor. The objective of this observational study was to describe the plerixafor prescription modalities in daily practice in Belgium. METHODS: This open-label, prospective, observational study was conducted in 11 Belgian centres in 114 patients with lymphoma (Hodgkin's and non-Hodgkin's lymphoma) or MM who were treated with plerixafor according to the SmPC between April 2011 and October 2012. Patients included in another clinical trial with plerixafor were excluded from the study. RESULTS: The use of plerixafor in patients with MM or lymphoma was effective, with a success rate (defined as a total yield >2×10(6) CD34+ cells/kg) of 77%, and well tolerated (one SAE reported). Optimal collection (defined as a total yield >4×10(6) CD34+ cells/kg) was obtained for 43% of the study population (31% in lymphoma patients, compared to 61% in patients with MM). The use of plerixafor was in line with the SmPC and the Belgian reimbursement criteria for all patients. CONCLUSION: This study is showing that the use of plerixafor according to Belgian reimbursement criteria results in similar efficacy and safety as in other centres and countries worldwide.

Immunotherapy in leukaemia.

Therapeutic cancer vaccination, e.g. by using tumour antigen-presenting dendritic cells (DCs) that 'educate' the immune system to recognise and attack tumour cells, represents a new concept of treatment in oncology. DCbased immunotherapy elicits both innate (NK) and adaptive (T cells) cellular responses correlated with clinical benefit. WT1 mRNA-transfected DCs emerge as a feasible and effective strategy to control residual disease in acute myeloid leukaemia (AML), in particular as a post-remission treatment to prevent full relapse. This innovative approach takes advantage of the intrinsic potential of the immune system to eradicate malignant disease.

Trends in embryo disposition decisions: patients' responses to a 15-year mailing program.

BACKGROUND: This study examined the responses of patients of a Belgian fertility center to mailed requests to make or renew an embryo disposition decision (EDD), over a period of 15 years, to investigate trends in the decisions. METHODS: A retrospective analysis was performed on a mailing program from 1992 to 2006, for patients, of the Department of Reproductive Medicine, Ghent University Hospital (Belgium), from whom embryos had been cryopreserved at least 2 years. RESULTS: In 15 years, 3840 EDD forms were prepared for 2334 couples or female patients. The number of forms increased from 21 in 1992 to 558 in 2006. Each year, around a third of the forms were not returned. In general, a quarter of patients who received more than one form never answered. Donation to others for reproduction was overall the least popular option and decreased over the years. The rising trend in decisions to discard reversed into a negative trend from the introduction of donation for science (1997). Since then, donation for science has been the most popular option and its popularity increased with time. In 15 years, 2504 embryos were donated for science. More than a quarter of the patients who chose more than one final EDD in different years did not select the same EDD the second time. CONCLUSIONS: This study showed a positive trend in donation for science and a negative trend in donation to others and discarding. A substantial number of individual patients chose different types of EDDs in consecutive mailings, which shows that advance EDD directives should be used with caution.

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium.

The prognosis of multiple myeloma patients has significantly improved since the introduction of the novel agents thalidomide, bortezomib and lenalidomide. We report the data of a medical need programme with lenalidomide plus dexamethasone, conducted in Belgium between August 2007 and March 2008, and including 98 relapsed refractory multiple myeloma patients. In addition to chemotherapy and steroids, all patients had received prior treatment with bortezomib, and 84% of them had been exposed to thalidomide. In 52 patients response data could be retrieved by post-hoc analysis. A partial remission or better was achieved in 52% (49% partial and 3% complete response) of patients, despite a median of 5 previous anti-myeloma treatment lines. Responses were rapid while the majority of patients received lenalidomide with once weekly (also called low-dose) dexamethasone. Treatment with lenalidomide plus dexamethasone did prolong overall survival by nearly half a year in this population with end-stage myeloma. Overall response and quality of response were independent of previous response to thalidomide and bortezomib, although the time to progression tended to be shorter in thalidomide- and bortezomib-refractory patients. It can be concluded that lenalidomide plus dexamethasone is an effective and safe treatment regimen in highly refractory multiple myeloma patients, and that these responses are irrespective of previous exposure or sensitivity to thalidomide and bortezomib.

Multicentric plasma cell variant Castleman's disease presenting with cutaneous vasculitis and pulmonary parenchymal involvement in a patient with ankylosing spondylitis: case report and review of the literature.

We present a case of the multicentric plasma cell variant of Castleman's disease (CD) with two rare manifestations. The patient consulted us because of cutaneous vasculitis of the lower limbs, while constitutional symptoms were nearly absent. Imaging studies also revealed pulmonary parenchymal involvement. Furthermore, our patient is the first case in whom association of ankylosing spondylitis with CD is reported. In addition, we present a review of the literature with emphasis on the clinical presentation of CD and its difficult discrimination from autoimmune and infectious disorders. An overview of the therapeutic options is also provided.

Plerixafor in poor stem cell mobilizers: the Belgian Compassionate Use Program.

INTRODUCTION: Currently available stem cell mobilizing regimens (G-CSF +/- chemotherapy) show high failure rates, especially in heavily pretreated patients. Plerixafor, a new stem cell mobilizing agent blocking the CXCR4-SDF-1 interaction, offers a new strategy for stem cell mobilization, especially in poor mobilizers.This study reports on the outcome of the Belgian compassionate use program (CUP). MATERIALS AND METHODS: Between July 2008 and July 2009, 14 Belgian transplant centres participated in plerixafor CUP. In total, 22 poor stem cell mobilizers were included. Patients who previously failed stem cell mobilization received a combination of G-CSF (morning of Day 1-5) and plerixafor (evening of Day 4). Apheresis was performed on Day 5. G-CSF, plerixafor and apheresis were continued until at least 2 x 10(6)/kg CD34+ cells were obtained in a maximum of 3 collections. RESULTS: A mean of 2 plerixafor administrations was needed to reach > or = 2 x 10(6)/kg CD34+ cells. The overall cumulative success rate (defined as the proportion of patients achieving a successful collection after a maximum of 3 apheresis days) was 64%. Half of the heavily pretreated patients ( 3 prior chemotherapy regimens) could be mobilized successfully. Patients who received < or = 2 prior chemotherapy regimens mobilized successfully in 75% of the cases. Thirteen patients (59.1%) underwent autologous stem cell transplantation with normal neutrophil and platelet recovery times. CONCLUSION: For patients failing previous mobilization attempts, the combination of plerixafor and G-CSF is a successful mobilizing strategy, even in poor mobilizers who received > or = 3 prior chemotherapy regimens.

To continue or discontinue storage of cryopreserved embryos? Patients' decisions in view of their child wish.

OBJECTIVE Cryopreservation of supernumerary embryos resulting from IVF treatment offers extra chances to conceive. The objective of this study is to describe patients' decisions to continue or discontinue storage of their embryos after a minimum storage period of 2 years. METHODS Female patients who had embryos stored at the Infertility Centre of the Ghent University Hospital (Belgium) were sent a mail questionnaire to be completed anonymously. RESULTS The questionnaire had a response rate of 79% (326/412). After an embryo storage period of at least 2 years, 40% of the couples who were still together wished to continue storage of their embryos. Half of these had no concrete plans for a transfer and wanted to postpone the decision or keep all options open. For those who decided to discontinue storage (60%), the main reason was the completion of their families. Despite the fact that the patients' child wish was the main factor in their storage decision, two groups of patients with distinct profiles made decisions that were inconsistent with their child wish: those who wanted to continue storage while not wanting a(nother) child (7% of those with no child wish), and those who wanted a(nother) child but decided to discontinue storage (25% of those with a child wish). Overall, these patients more often expressed emotional difficulties regarding this decision. CONCLUSIONS This study demonstrates the importance of gaining more insight into patients' embryo storage decisions (along with their embryo disposition decisions) and into the emotional factors playing a role in patients' decision-making.

Reflections by patients who undergo IVF on the use of their supernumerary embryos for science.

Interviews were conducted with patients undergoing treatment at the department for reproductive medicine at the University Hospital of Ghent, Belgium to describe how patients think about the use of embryos for science and how patients' views are related to their decision whether or not to donate their supernumerary embryos for science. Most participants knew little about the use of embryos for science. The perception of science and scientists, rather than the perception of the embryo, played an important role in the disposition decision making. The feeling of not having control over what would happen to their embryo and the fear that scientists would allow their embryo to develop into children were the main arguments against donation. This showed the importance of information about scientific research with embryos, such as the 14-day limit to keep embryos alive. Half of the participants pictured the medical team as the requesting party for their embryos and those who were not willing to donate indicated that they could be persuaded when asked directly by their caregivers. In conclusion, this study suggests that the perception of science, rather than the perception of the embryo, plays an important role in the decision to donate for science.

Efficient mRNA electroporation of peripheral blood mononuclear cells to detect memory T cell responses for immunomonitoring purposes.

To date, the number of immunotherapy vaccines in clinical trials increases exponentially. To evaluate the efficacy of these clinical vaccination trials, we fervently need cellular immunomonitoring tools. In this study, we present a newly developed short-time assay which allows direct ex vivo analysis of multi-epitope antigen-specific T cell immune responses. This novel method is based on mRNA electroporation of isolated peripheral blood mononuclear cells (PBMC). Fresh and cryopreserved PBMC of both healthy volunteers as well as of allogeneic stem cell transplanted patients enrolled in a cytomegalovirus (CMV) dendritic cell vaccination trial were electroporated with CMV pp65-encoding mRNA. Using a direct IFN-gamma EliSPOT and intracellular cytokine flow cytometry we detected significantly higher numbers of CMV pp65-specific IFN-gamma-secreting T cells as compared to the assay with non-treated PBMC and as compared to PBMC electroporated with mRNA coding for an irrelevant protein. Compared to conventional methods to evaluate T cell-mediated immune responses, this method is time-saving and less labor-intensive because it obviates the need for in vitro cultured antigen-presenting cells and because an overnight incubation is sufficient for activation of T cells. Moreover, the use of CMV pp65-encoding mRNA will broaden the immune response because it covers every epitope with potential relevance. This is a major advantage compared to the recognition of a single epitope covered by a HLA-restricted peptides. In summary, we developed a highly efficient mRNA electroporation protocol for fresh and cryopreserved PBMC. This novel method is a rapid and elegant tool and will be convenient for monitoring the cellular immune status of patients in a clinical vaccination setting.

Long-term epidemiology of bacterial susceptibility profiles in adults suffering from febrile neutropenia with hematologic malignancy after antibiotic change.

OBJECTIVE: The aim of this study was to investigate the epidemiology and antibiotic susceptibility profiles of isolated bacterial organisms in relation to empiric treatment of neutropenic fever over a 15-year period. METHODS: All patients with or at risk for febrile neutropenia and treated in the hematology ward of the Antwerp University Hospital during 1994-2008 were prospectively included. Skin, blood, and urine cultures were taken. Oral quinolone prophylaxis was started in patients with neutropenia without fever. Empiric starting therapy consisted of amikacin in combination with cefepime. RESULTS: A total of 3624 bacteria were isolated. The most common pathogens were coagulase-negative Staphylococci (46%), followed by Escherichia coli (25%), Enterobacteriaceae (15.6%), Staphylococcus aureus (7.2%), and Pseudomonas aeruginosa (3.8%). The balance between Gram-positive and Gram-negative bacteria remained stable, with a majority of Gram-positive bacteria. A shift from oxacillin-sensitive to oxacillin-resistant coagulase-negative Staphylococci was observed. Regarding susceptibility patterns, no vancomycin resistance was detected in coagulase-negative Staphylococci or in S. aureus. The E. coli susceptibility rates remained stable. However, 66% of bloodstream infections were ciprofloxacin-resistant. A reduced susceptibility of P. aeruginosa strains to meropenem was noticed. CONCLUSIONS: Improvement in antibiotic susceptibility of inducible Enterobacteriaceae following a switch of empiric antibiotic therapy was maintained 15 years after starting the latter treatment. Further improvement in antibiotic susceptibility of these bacteria to ceftazidime was observed, but continuous vigilance is warranted.

Patients' conceptualization of cryopreserved embryos used in their fertility treatment.

BACKGROUND: Although IVF treatments using cryopreserved embryos are offered by most infertility centres, little is known about patients' opinions regarding treatment using these embryos. The objective of this study is to describe how patients think about (treatment with) cryopreserved embryos. METHODS: In-depth interviews based on the method of interpretative phenomenological analysis were conducted with patients undergoing IVF/ICSI treatment at the Department of Reproductive Medicine of the Ghent University Hospital between May and July 2006. Seven couples (one couple considered as one participant) and 11 female patients who attended the clinic without their partner were interviewed. RESULTS: Most participants knew little about medical-technical procedures involved in treatment with cryopreserved embryos. This was compensated by a high confidence in the medical team. However, seven of the eighteen participants thought the quality of cryopreserved embryos diminished during the storage period. A lack of knowledge about medical-technical procedures was compensated by metaphors related to other domains of experience, especially kitchen metaphors: this might add to the belief that frozen embryos have an expiry date. However, none of the patients who considered treatment with cryopreserved embryos as less effective ever thought of refusing this type of treatment or discussed this with medical staff. In addition, patients rarely discussed the moral status of their cryopreserved embryos. CONCLUSIONS: The beliefs of infertile patients about (the effectiveness of treatment with) cryopreserved embryos encompass misconceptions, and doubts and fears which may influence their decision-making but which are seldom discussed with the medical staff.

Infertility patients' beliefs about their embryos and their disposition preferences.

BACKGROUND: Little research has been done on how beliefs of infertility patients about their embryos are related to their disposition decisions. The objective of this study was to describe how patients speak about their embryos, in moral (e.g. status) and non-moral terms, and to investigate how patients' narratives are related to their disposition preferences. METHODS: In-depth interviews based on the method of interpretative phenomenological analysis were conducted with patients undergoing IVF/ICSI treatment between May and July 2006. RESULTS: Seven couples and 11 female patients were interviewed. Six major themes emerged from the narratives of the participants when they spoke about their embryos: (i) a medical-technical perspective; (ii) feelings; (iii) genetic link to oneself and/or one's partner; (iv) symbolic meaning of the relationship between the infertile partners; (v) moral status and (vi) instrumental value. All but two participants spontaneously considered the embryo disposition options as a two-stage decision sequence. In the first step, they considered donation to another couple for reproductive purposes. At this stage, the presence of the themes 'genetic link' and 'symbol of the relationship' was linked with a clear reluctance to donate. In the second step of the decision-making process, the option of donation for research and discarding were considered. At this stage, participants' confidence in medical science and the instrumental value they attached to the embryo were related to their decisions. CONCLUSIONS: Patients' conceptualization of their embryos plays an important role in embryo disposition decisions. Our research showed that patients deal with these decisions in a two-stage decision sequence.

Proinflammatory response of human leukemic cells to dsRNA transfection linked to activation of dendritic cells.

Leukemic cells exert immunosuppressive effects that interfere with dendritic cell (DC) function and hamper effective antileukemic immune responses. Here, we sought to enhance the immunogenicity of leukemic cells by loading them with the double-stranded (ds) RNA Toll-like receptor 3 (TLR3) ligand polyriboinosinic polyribocytidylic acid (poly(I:C)), mimicking viral infection of the tumor cells. Given the responsiveness of DC to TLR ligands, we hypothesized that the uptake of poly(I:C)-loaded leukemic cells by immature DC (iDC) would lead to DC activation. Primary acute myeloid leukemia (AML) cells and AML cell lines markedly responded to poly(I:C) electroporation by apoptosis, upregulation of TLR3 expression, enhanced expression of major histocompatibility complex (MHC) and costimulatory molecules and by production of type I interferons (IFN). Upon phagocytosis of poly(I:C)-electroporated AML cells, DC maturation and activation were induced as judged by an increased expression of MHC and costimulatory molecules, production of proinflammatory cytokines and an increase of T helper 1 (T(H)1)-polarizing capacity. These immune effects were suboptimal when AML cells were passively pulsed with poly(I:C), indicating the superiority of poly(I:C) transfection over pulsing. Our results demonstrate that poly(I:C) electroporation is a promising strategy to increase the immunogenicity of AML cells and to convert iDC into activated mature DC following the phagocytosis of AML cells.

Acute myeloid leukaemia of mixed megakaryocytic and erythroid origin: a case report and review of the literature.

We report the case of a 78-year-old man who presented with acute myeloid leukaemia showing subpopulations of cells expressing platelet-associated markers and the presence of a pan-myeloid component, besides glycophorin A-positive cells. Most of the immature cells had a proerythroblast-like morphology and we classified this case as an FAB-M6 variant, as suggested by Bain (1). According to the WHO classification, this leukaemia fulfilled the criteria of'AML with multilineage dysplasia' (2). Immunophenotyping characteristics showed two distinct aberrant subpopulations, a young pan-myeloid (CD45+ with low density, CD34+, CD117+, CD13+, CD33+, partial cytoplasmic myeloperoxidase (MPO)+) population with platelet-associated markers (CD41+, CD42+, CD61+) and a CD45+, CD117+, CD34- population with partial CD235a positivity indicative for erythroid maturation. This case belongs to the group of 'early' erythroblastic leukaemias where a subset of progenitor cells present with erythroid-megakaryocyte bipotentiality or are blocked at an early BFU-E (burst-forming unit erythrocyte)-like stage of erythroid differentiation (11, 12, 13).

Bortezomib-induced Sweet's syndrome.

Sweet's syndrome is an uncommon acute skin disease, associated with a variety of medical problems. The drug-induced variant is even rarer. We describe two cases of this syndrome associated with the administration of the proteasome inhibitor bortezomib. The diagnostic criteria for drug-induced Sweet's syndrome as proposed by Walker and Cohen were fulfilled. Vasculitis and neutrophilic eccrine hidradenitis were excluded.