Aurea Cervera

Finding the cause of fever of unknown origin can sometimes be a real challenge. We present an adolescent whose diagnosis was achieved after 4 months of fever onset by performing a positron emission tomography (PET)–CT. A young woman presented with prolonged, intermittent fever along with inflammatory and iron deficiency anaemia, loss of weight and abdominal and chest pain. First investigational studies showed high-titre positive antinuclear antibodies, extractable nuclear antibodies and anti-Sjögren's-syndrome-related antigen a autoantibodies (anti-SSA), and mild pericardial effusion and aortic regurgitation, but without meeting criteria for systemic lupus erythematosus. She had maxillary sinusitis that did not resolve with antibiotics. Further study displayed elevated calprotectin in faeces. After normal abdominal ultrasound and CT, an intestinal MRI showed thickening of the terminal ileum, orienting towards an inflammatory bowel disease. A colonoscopy showed only minor macroscopic changes. A PET–CT scan was finally requested, which exhibited a diffuse increase in metabolism in the wall of the thoracic and abdominal aortas, suggesting Takayasu’s arteritis.

227 Background: A.A has been approved for the treatment of mCRPC before and after docetaxel. The standard regime consists on daily A.A. 1.000 mg in a fasting state along with prednisone 10mg q.d. However, data from pharmacokinetic (PK) studies in patients (pts) and healthy volunteers has revealed a significant food-effect with up to 7-10 folder increase in area under plasma concentration-time curve (AUC) when A.A is given with food, specially with fat content, [Chi KN, J Clin Pharmacol 2015]. Methods: ABIFOOD is a phase I, randomized trial to evaluate the short and long-term effect of diet on the PKs of A.A. in pts with mCRPC who have progressed to docetaxel. Eligible pts include men ≥ 18 years old with mCRPC, ECOG performance status (PS) < 2 and an adequate organ function. Pts are randomly assigned to receive 4-weekly cycles of 250 mg A.A with standard meal (Arm A), 250 mg A.A with high-fat meal (Arm B) or 1000 mg A.A in fasting conditions (Arm C). PK analyses are conducted at week 1 (W1) and cycle 5. Results: Fifteen pts (5, 3 and 7 in arms A, B and C respectively) have been included and 6 are still on treatment. Median age is 72, 97% have ECOG-PS 1. Gleason Score is > 8 in 6 (40%) pts.Geometric mean abiraterone [AUC (ng.h/ml) (IQR)] at W1 did not significantly differ between treatment arms [arm A: 404.68 (368.4 - 488.2), arm B: 372 (334.6 - 440.5) arm C: 656.51 (387.8 – 1144.5) p 0.15]. PK data did not influence activity or toxicity. Progression free survival was 8.50, 6.33 and 4.86 months in Arms A, B and C respectively (p 0.53). One patient in arm A is still on treatment after 17 cycles. Conclusions: The administration of lower doses of A.A with food [regardless the fat content], might achieve comparable plasma levels to standard dosing with no detriment in efficacy or toxicity parameters. The study is actively recruiting and data on additional pts and long term PK parameters will be presented. Clinical trial information: EudraCt number: 2012-003226-25.

In the 5′ untranslated region (5′UTR), which is transcribed but not translated and is involved in posttranscriptional regulation of the gene promoting and stabilizing the mRNA translation, several mutations associated with mild β-thalassemia (β-thal) have been described. One of these, the +20 (C>T) mutation, is described in the HbVar database as a mutation responsible for β⁺-thal. In heterozygote cases, it gives rise to a phenotype of β-thal minor and β-thal intermediate (β-TI) when the mutation is associated with β⁺ IVS-II-745 (C>G). To clarify if this mutation is responsible for β⁺-thal, we studied nine cases where we found an association of the +20 and IVS-II-745 mutations. All patients were carriers of four α genes. Three patients carried β-thal major (β-TM), two were compound heterozygotes for IVS-II-745 and codon 8 (–AA) or codon 39 (C>T), and the third was homozygous for IVS-II-745; all had the +20 mutation in the 5′UTR. The remaining patients showed the mutation IVS-II-745 associated with a replacement of C>T at nucleotide (nt) +20 of the 5′UTR. Contrary to reports in the HbVar database, the +20 mutation should be considered as an innocuous single nt polymorphism associated with the IVS-II-745 mutation in cis.

Background. In Europe, imported malarial cases occur in returning travelers and immigrants mostly from African countries. There have been an increasing

Objective: The aim of this study was to characterize the lymphocyte and the hematopoietic stem and progenitor cell (HPC) subsets of cryopreserved premature cord blood (PCB) compared to term cord blood (TCB) by flow cytometry, to study the influence of birth conditions, and to assess its availability for transplantation. Materials and methods: Four‐color flow cytometric analysis was performed on 43 PCB and 40 TCB cryopreserved samples using a panel of 24 different mAbs, directed against lymphoid and HPC surface markers. The CB volume was estimated by the weight of the newborn to determine the absolute MNC and CD34⁺ cell content/CB sample. Clinical and obstetrical data were recovered. Statistical comparisons and a multiple regression analysis were performed. Results: No consistent differences were found in the mononuclear cell (MNC) or CD34⁺ cell concentration (×10⁶/L) between PCB and TCB. The percentage of primitive HPC (CD34⁺CD38⁻, CD34⁺CD38⁻CD90⁻HLA‐DR⁻, CD34⁺CD38⁻CD90⁻HLA‐DR⁺) and primitive lymphoid progenitors (CD34⁺CD7⁺, CD34⁺CD7⁺CD19⁻CD117⁻) were higher in PCB than in TCB. Correspondingly, TCB had an increased percentage of committed HPC. No sample of PCB contained >2 × 10⁷ MNC/kg (and only 48% had >1 × 10⁵ CD34⁺ cells) for a recipient of 20 kg body wt, as the minimum threshold recommended for CB transplantation. Obstetrical factors modulated mainly lymphocyte subsets and fewer HPC subpopulations. Acute fetal distress increased CD34⁺ cells, especially the immature subsets. Maternal treatment with dexamethasone and intrauterine growth retardation decreased CD3⁺ cells. No other obstetrical factors played a detrimental effect on CB cells if used for transplantation. Conclusion: PCB is richer in immature cells both in lymphocyte and HPC populations, and its use for transplantation, at least in special cases, should be reconsidered. Am. J. Hematol. 81:397–410, 2006.

Central nervous system involvement in Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, is manifested mainly by diabetes insipidus reflecting local infiltration of Langerhans cells into the posterior pituitary or hypothalamus. We describe two patients with progressive spinocerebellar degeneration appearing 4 and 6 years after the initial diagnosis of LCH. No correlation was found between the clinical course of the disease or its treatment and the neurological impairment. An extensive search for metabolic, toxic, neoplastic, and hereditary etiologies for progressive cerebellar degeneration was negative.

Late recurrence of neuroblastoma is uncommon. We report five patients who developed recurrent disease more than five years after diagnosis and review the literature on this subject.