The alteration of lipid metabolism in burkitt lymphoma identifies a novel marker: adipophilin

Background: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. Methods and Results: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymphoma and in other B-cell aggressive lymphoma cases. Gene expression profile indicated a significant over-expression of the adipophilin gene and marked up-regulation of other genes involved in lipid metabolism in Burkitt lymphoma. These findings were confirmed by immunohistochemistry on a series od additional histological samples: 45 out of 47 BL cases showed strong adipophilin expression, while only 3 cases of the 33 of the not-Burkitt lymphoma category showed weak adipophilin expression (p<0.05). Conclusions: Our preliminary results suggest that lipid metabolism is altered in BL, and this leads to the accumulation of lipid vacuoles. These vacuoles may be specifically recognized by a monoclonal antibody against adipophilin, which may therefore be a useful marker for Burkitt lymphoma because of its peculiar expression pattern. Moreover this peptide might represent an interesting candidate for interventional strategies. © 2012 Ambrosio et al

Lymphomas in sub-Saharan Africa - what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research?

Approximately 30 000 cases of non-Hodgkin lymphoma (NHL) occur in the equatorial belt of Africa each year. Apart from the fact that Burkitt lymphoma (BL) is very common among children and adolescents in Africa and that an epidemic of human immunodeficiency virus (HIV) infection is currently ongoing in this part of the world, very little is known about lymphomas in Africa. This review provides information regarding the current infrastructure for diagnostics in sub-Saharan Africa. The results on the diagnostic accuracy and on the distribution of different lymphoma subsets in sub-Saharan Africa were based on a review undertaken by a team of lymphoma experts on 159 fine needle aspirate samples and 467 histological samples during their visit to selected sub- Saharan African centres is presented. Among children (age), BL accounted for 82% of all NHL, and among adults, diffuse large B-cell lymphoma accounted for 55% of all NHLs. Among adults, various lymphomas other than BL, including T-cell lymphomas, were encountered. The review also discusses the current strategies of the International Network of Cancer Treatment and Research on improving the diagnostic standards and management of lymphoma patients and in acquiring reliable clinical and pathology data in sub- Saharan Africa for fostering high-quality translational research

Clonality analysis of immunoglobulin gene rearrangement by next-generation sequencing in endemic burkitt lymphoma suggests antigen drive activation of bcr as opposed to sporadic burkitt lymphoma

Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. METHODS: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). RESULTS: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. CONCLUSIONS: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development

Notulae to the Italian native vascular flora: 10

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions for taxa in the genera Artemisia, Chaetonychia, Cirsium, Cynanchum, Genista, Hieracium, Iberis, Melica, Misopates, Myosotis, Thalictrum, Trifolium, Utricularia, Veronica, and Vicia. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as supplementary material

Hemophagocytic inflammatory syndrome in ADA-SCID: report of two cases and literature review

Hemophagocytic inflammatory syndrome (HIS) is a rare form of secondary hemophagocytic lymphohistiocytosis caused by an impaired equilibrium between natural killer and cytotoxic T-cell activity, evolving in hypercytokinemia and multiorgan failure. In the context of inborn errors of immunity, HIS occurrence has been reported in severe combined immunodeficiency (SCID) patients, including two cases of adenosine deaminase deficient-SCID (ADA-SCID). Here we describe two additional pediatric cases of ADA-SCID patients who developed HIS. In the first case, HIS was triggered by infectious complications while the patient was on enzyme replacement therapy; the patient was treated with high-dose corticosteroids and intravenous immunoglobulins with HIS remission. However, the patient required HLA-identical sibling donor hematopoietic stem cell transplantation (HSCT) for a definitive cure of ADA-SCID, without HIS relapse up to 13 years after HSCT. The second patient presented HIS 2 years after hematopoietic stem cell gene therapy (GT), secondarily to Varicella-Zoster vaccination and despite CD4+ and CD8+ lymphocytes’ reconstitution in line with other ADA SCID patients treated with GT. The child responded to trilinear immunosuppressive therapy (corticosteroids, Cyclosporine A, Anakinra). We observed the persistence of gene-corrected cells up to 5 years post-GT, without HIS relapse. These new cases of children with HIS, together with those reported in the literature, support the hypothesis that a major dysregulation in the immune system can occur in ADA-SCID patients. Our cases show that early identification of the disease is imperative and that a variable degree of immunosuppression could be an effective treatment while allogeneic HSCT is required only in cases of refractoriness. A deeper knowledge of immunologic patterns contributing to HIS pathogenesis in ADA-SCID patients is desirable, to identify new targeted treatments and ensure patients’ long-term recovery

Notulae to the Italian native vascular flora: 8

In this contribution, new data concerning the distribution of native vascular flora in Italy are presented. It includes new records, confirmations, exclusions, and status changes to the Italian administrative regions for taxa in the genera Ajuga, Chamaemelum, Clematis, Convolvulus, Cytisus, Deschampsia, Eleocharis, Epipactis, Euphorbia, Groenlandia, Hedera, Hieracium, Hydrocharis, Jacobaea, Juncus, Klasea, Lagurus, Leersia, Linum, Nerium, Onopordum, Persicaria, Phlomis, Polypogon, Potamogeton, Securigera, Sedum, Soleirolia, Stachys, Umbilicus, Valerianella, and Vinca. Nomenclatural and distribution updates, published elsewhere, and corrigenda are provided as Suppl. material 1

Treatment outcome among children under-five years hospitalized with severe acute malnutrition in St. Mary’s hospital Lacor, Northern Uganda

BACKGROUND: Severe malnutrition contributes to more than 60 % of deaths in children in developing countries. The minimum international standard set for management of severe acute malnutrition is a cure rate of at least 75 % and death rate of less than 10 %, yet the outcome of severely malnourished children treated in most hospitals in developing countries remain poor. This study was conducted to determine the treatment outcomes among severely malnourished children admitted at St. Mary's hospital Lacor in Northern Uganda during a one year period in order to inform clinical decisions to maximize management of severely malnourished children. METHODS: This was a retrospective study involving 251 severely malnourished children treated at St. Mary's hospital Lacor within a one year period in 2014. Patients' medical records in the facility therapeutic feeding unit were retrospectively reviewed using a check list to collect basic demographic, clinical, and treatment outcome data of the sampled study patients. The UNICEF treatment outcome categories were used, and further grouped into three summary categories: "successful (cured)", "died" and "potentially unsatisfactory". Data were entered, cleaned and analyzed using statistical package SPSS version 13. For categorical data, proportions with 95 % confidence intervals, odds ratio and Chi-square test to compare different groups were used. Multivariate analysis using logistic regression was used to analyze the association between treatment outcome and potential associated factors. P values less than 0.05 was considered for statistical significance. RESULTS: The study consisted 251 patients and the treatment outcome was successful (cured) in 168 (66.9 %) and potentially unsatisfactory in 53 (21.2 %), while 30 (11.9 %) died. Hypothermia and HIV infection were the factors significantly associated with mortality among the severely malnourished children in the current study. CONCLUSIONS: The treatment cure rate of severely malnourished children admitted at St. Mary's hospital Lacor of 66.9 % is below the accepted standard of least 75 % cure rate. A high proportion of patients died (11.9 %) or defaulted (8.0 %). Hypothermia and HIV infection were the factors significantly associated with mortality. We recommend that in order to address the high default rate, home based care through the outpatient therapeutic care should be strengthened

Bilateral proptosis as an early manifestation of juvenile myelomonocitic leukemia in an African child

We report bilateral proptosis as the unusual initial presentation of juvenile myelomonocytic leukemia in a Ugandan child. Juvenile myelomonocytic leukemia was diagnosed with complete blood count and bone marrow aspiration biopsy. This is the first description of orbital involvement occurring in the setting of juvenile myelomonocytic leukemia, despite leukemic orbital infiltration is relatively common in the middle East, Asia, and Africa. In general, simultaneous neoplastic involvement of both orbits at presentation is also a rare finding, bur appears to be highly likely in leukemic children

A Case of William&rsquo;s Syndrome in a Ugandan Child: A Feasible Diagnosis Even in a Low-Resource Setting

Background: Williams&ndash;Beuren syndrome (WS) is a rare, complex, congenital developmental disorder including cardiovascular manifestations, intellectual disability and a peculiar cognitive and behavior profile. Supravalvular aortic stenosis (SVAS) is the most frequent cardiovascular abnormality in WS children. Data on WS patients in sub-Saharan Africa are scarce. A genetic study is usually required for a definite diagnosis, but genetic testing is often unavailable in developing countries and the combination of a typical clinical phenotype and echocardiographic profile helps to confirm the diagnosis. Case Report: We report the case of a 5-year-old Ugandan child admitted to a large no profit hospital after he was initially managed as a case of infective endocarditis. A physical examination revealed the typical features of WS. A cardiac echo showed severe SVAS (peak gradient 80 mmHg) with a normal anatomy and function of the aortic valve and mild valvular pulmonary stenosis. The child also had a moderate intellectual disability and a characteristic facies consistent with WS. Conclusion: We present the first reported case of WS in Uganda. Cardiac echo and a characteristic clinical picture could be enough to exclude more common causes of heart failure (i.e., rheumatic heart disease) and to make the diagnosis even when specific genetic tests are not available

Toward Reference Intervals of ARSA Activity in the Cerebrospinal Fluid: Implication for the Clinical Practice of Metachromatic Leukodystrophy

BACKGROUND: Cerebrospinal fluid (CSF) has emerged as a sensitive matrix for the screening of biomarkers for diagnosis and clinical follow-up of diseases with neurological manifestations, including some lysosomal storage disorders. In this study, we assessed the range of values of arylsulfatase A (ARSA) activity in the CSF of pediatric and adult donors, and in pediatric patients who underwent gene therapy for metachromatic leukodystrophy (MLD).METHODS: A cohort of 56 CSF samples was included in the study: pediatric donors (n=36), adult donors (n=9), and MLD patients (n=11) at different timepoints [pre-gene therapy (GT), post-GT+1 Year, post-GT+2 Years, post-GT+3 Years]. We have used our fluorometric assay for the determination of ARSA activity. The total protein content in the samples was also evaluated.RESULTS: We discovered that ARSA activity was higher in pediatric donors (geometric mean: 1.039nmol/mg/h; 95% range: 0.859-1.258nmol/mg/h) compared to adults (geometric mean: 0.305nmol/mg/h; 95% range: 0.214-0.435nmol/mg/h). No ARSA activity was detected in the CSF of MLD patients pre-GT, whereas ARSA activity was stably expressed and almost restored to range of values of pediatric donors in MLD patients post-GT+3 Years with a geometric mean of 0.822nmol/mg/h (95% range: 0.580-1.165nmol/mg/h).CONCLUSIONS: This study establishes range of values of ARSA activity in the CSF for MLD clinical practice. The observed ranges of ARSA activities in CSF exhibited an unpredicted age dependence and, in turn, revealed the need of using pediatric ARSA activity for evaluating the restoration of the enzyme activity during the therapy of MLD