Lymphoma of the sphenoid sinus presenting as abducens nerve palsy in a child

Primary sphenoid sinus malignancy with abducens nerve palsy is rare in the paediatric population. We report the first case of bilateral isolated abducens nerve palsy secondary to primary T‐cell anaplastic lymphoma of the sphenoid sinus in the absence of radiological evidence of bony destruction or malignant invasion in an 8‐year‐old boy. This case highlights the importance of understanding surgical anatomy of the sphenoid sinuses and cavernous sinuses, and to maintain a high index of suspicion when a patient is presented with simultaneous palsy of any of the cranial nerves within the cavernous sinus and sphenoid sinus disease, despite possible disparities between clinical features and radiological findings. Prompt surgical exploration and biopsy of sphenoid sinus is imperative to establish the diagnosis and to initiate treatment in order to avoid further progression of disease or other complications.     

The impact of islet mass,number of transplants,and time between transplants on graft function in a national islet transplant program

The UK islet allotransplant program is nationally funded to deliver one or two transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus two transplants; time between two transplants and graft survival (stimulated C-peptide >50 pmol/L) and function. In total, 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23 (68%) single and 47 (94%) (p = .002) two transplant recipients (separated by [median (IQR)] 6 (3–8) months). 64% recipients of one or two transplants with uninterrupted function at 12 months sustained graft function at 6 years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p < .01). Despite 1.9-fold greater transplanted mass in recipients of two versus one islet infusion (12 218 [9291–15 417] vs. 6442 [5156–7639] IEQ/kg; p < .0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta ?0.35; p = .02). Graft survival over the first 12 months was greater in recipients of two versus one islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function.     

Cell-surface antigen profiling of pediatric brain tumors: B7-H3 is consistently expressed and can be targeted via local or systemic CAR T-cell delivery

BackgroundImmunotherapy with chimeric antigen receptor (CAR) T cells is actively being explored for pediatric brain tumors in preclinical models and early phase clinical studies. At present, it is unclear which CAR target antigens are consistently expressed across different pediatric brain tumor types. In addition, the extent of HLA class I expression is unknown, which is critical for tumor recognition by conventional αβTCR T cells.MethodsWe profiled 49 low- and high-grade pediatric brain tumor patient-derived orthotopic xenografts (PDOX) by flow analysis for the expression of 5 CAR targets (B7-H3, GD2, IL-13Rα2, EphA2, and HER2), and HLA class I. In addition, we generated B7-H3-CAR T cells and evaluated their antitumor activity in vitro and in vivo.ResultsWe established an expression hierarchy for the analyzed antigens (B7-H3 = GD2 >> IL-13Rα2 > HER2 = EphA2) and demonstrated that antigen expression is heterogenous. All high-grade gliomas expressed HLA class I, but only 57.1% of other tumor subtypes had detectable expression. We then selected B7-H3 as a target for CAR T-cell therapy. B7-H3-CAR T cells recognized tumor cells in an antigen-dependent fashion. Local or systemic administration of B7-H3-CAR T cells induced tumor regression in PDOX and immunocompetent murine glioma models resulting in a significant survival advantage.ConclusionsOur study highlights the importance of studying target antigen and HLA class I expression in PDOX samples for the future design of immunotherapies. In addition, our results support active preclinical and clinical exploration of B7-H3-targeted CAR T-cell therapies for a broad spectrum of pediatric brain tumors.     

Bacteroides fragilis concealed in an infant with Escherichia coli meningitis

Anaerobic meningitis in infants is rare, therefore a high index of clinical suspicion is essential as routine methods for processing cerebrospinal fluid (CSF) do not detect anaerobes and specific antimicrobial therapy is required. We present an infant with Escherichia coli meningitis where treatment‐resistance developed in association with culture negative purulent CSF. These features should have alerted us to the presence of anaerobes, prompting a search for the causes of polymicrobial meningitis in infants.     

Genomic diversity of the acquired immune deficiency syndrome virus HTLV-III: different viruses exhibit greatest divergence in their envelope genes.

Converging lines of research have linked human T-cell lymphotropic virus type III (HTLV-III) to the pathogenesis of the acquired immune deficiency syndrome. A characteristic feature of this virus is its genomic heterogeneity, which occurs to varying degrees in different viral isolates. To define further the nature and extent of these genomic changes, we compared the molecularly cloned genomes of two variant HTLV-III isolates by extensive restriction enzyme mapping and heteroduplex thermal melt analysis. Both viral isolates were found to be highly related to each other throughout their entire genomic complement, yet they differed markedly in their restriction enzyme maps. Electron microscopic heteroduplex analysis revealed several distinct regions of divergence located almost exclusively in the part of the genome that encodes the viral envelope gene. In vitro culture of one of these viruses over a period of 3 months did not result in any genomic changes as determined by restriction analysis of viral DNA. These results, as well as the recently published nucleotide sequences of other HTLV-III isolates, indicate that the most substantial variation among HTLV-III isolates is located in the envelope. These findings raise the possibility that viral isolates from different individuals could have important biological differences in their envelope antigens, a consideration relevant to ongoing attempts to develop a vaccine against HTLV-III.     

Assessment of immunochemical methods for determining low concentrations of albumin in urine

Four immunochemical methods (radioimmunoassay, RIA; radial immunodiffusion, RID; immunoturbidimetry, IT; enzyme-linked immunosorbent assay, ELISA) for measuring urinary albumin at low concentrations were assessed for their assay characteristics and practicability. Precision and accuracy were comparable between the methods when studied individually. We made a method comparison, with RIA as reference, using urine samples from diabetic patients with albumin concentrations ranging from 1 to 120 mg/L. There was no significant systematic difference between RID and RIA, but IT and ELISA gave consistently lower values than RIA, the mean differences being 1.8 (p less than 0.01) and 9.7 mg/L (p less than 0.001), respectively. Random error, compared with that for RIA, was in increasing order: RID (residual SD = 3.8 mg/L); IT (4.3 mg/L); ELISA (7.3 mg/L). The difference between the methods increased with the albumin concentration. Operational cost was highest with IT, lowest with RIA. Capital cost was highest with RIA and lowest with RID, which required most technical skill. ELISA had intermediate overall costs.