The value of 18F-FDG-PET/CT imaging for sinonasal malignant melanoma

The aim this study was to evaluate imaging findings using position emission tomography (PET) in combination with computed tomography (CT) and 18F-fluorodeoxyglucose (18F-FDG) in sinonasal malignant melanoma (SNMM) of the head and neck in a retrospective analysis of a consecutive cohort of patients. 18F-FDG-PET/CT examinations were performed for initial staging and compared with CT or magnetic resonance tomography (MRI), and 18F-FDG-PET alone. Medical records were reviewed retrospectively with regard to the location and the size of the tumor. Furthermore, locoregional and distant metastases with a consecutive change in therapy detected by 18F-FDG-PET/CT were assessed. Ten patients suffering from sinonasal malignant melanoma were staged and followed by 18F-FDG-PET/CT imaging. A total of 34 examinations were obtained. 18F-FDG-PET/CT depicted all primary tumors adequately. Aside from one cerebral metastasis all regional and distant metastases were truly identified by using this method. In summary, if available, 18F-FDG-PET/CT is a valuable imaging modality for staging and re-staging sinonasal malignant melanoma to evaluate expansion of the primary tumor, locoregional disease, and distant metastase

A First Comparison of the responses of a He4-based fast-neutron detector and a NE-213 liquid-scintillator reference detector

A first comparison has been made between the pulse-shape discrimination characteristics of a novel $^{4}$He-based pressurized scintillation detector and a NE-213 liquid-scintillator reference detector using an Am/Be mixed-field neutron and gamma-ray source and a high-resolution scintillation-pulse digitizer. In particular, the capabilities of the two fast neutron detectors to discriminate between neutrons and gamma-rays were investigated. The NE-213 liquid-scintillator reference cell produced a wide range of scintillation-light yields in response to the gamma-ray field of the source. In stark contrast, due to the size and pressure of the $^{4}$He gas volume, the $^{4}$He-based detector registered a maximum scintillation-light yield of 750~keV$_{ee}$ to the same gamma-ray field. Pulse-shape discrimination for particles with scintillation-light yields of more than 750~keV$_{ee}$ was excellent in the case of the $^{4}$He-based detector. Above 750~keV$_{ee}$ its signal was unambiguously neutron, enabling particle identification based entirely upon the amount of scintillation light produced.Comment: 23 pages, 7 figures, Nuclear Instruments and Methods in Physics Research Section A review addresse

Further phenotypic heterogeneity of CoQ10 deficiency associated with Steroid Resistant Nephrotic Syndrome and novel COQ2 and COQ6 variants.

open16noWe descripe three patients with SRNS associated with pathogentic changes in two CoQ pathway genes: one novel homozygous COQ2 variant was identified in two cousins with adolescent-onset SRNS and mild neurological symptoms (Family 1); and one novel COQ6 variant was found in a child with early onset SRNS without deafness and neurological involvement (Family 2). (A, B) : families (C) : Sanger sequencing showing COQ2 change: NM_015697.7: c.1169G>C; NP_056512.5; p.Gly390Ala (c.1019G>C; p.Gly340Ala, according to KU877220 GenBank sequence) (D) : Sanger sequencing showing COQ6 change: NM_182476.2:c.782C>T; NP_872282.1:p.Pro261Leu. (E, F): Functional complementation in yeast. Serial dilutions of ΔCOQ2 and ΔCOQ6 yeast transformed with wild-type, the empty vector and the mutant alleles; complex II+III (C.II+C.III) and citrate synthase (CS) activities.embargoed_20180801Gigante, M; Diella, S; Santangelo, L; Trevisson, Eva; Acosta, Mj; Amatruda, M; Finzi, G; Caridi, G; Murer, L; Accetturo, M; Ranieri, E; Ghiggeri, Gm; Giordano, M; Grandaliano, G; Salviati, Leonardo; Gesualdo, L.Gigante, M; Diella, S; Santangelo, L; Trevisson, Eva; Acosta, Mj; Amatruda, M; Finzi, G; Caridi, G; Murer, L; Accetturo, M; Ranieri, E; Ghiggeri, Gm; Giordano, M; Grandaliano, G; Salviati, Leonardo; Gesualdo, L

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial.

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses ( 650.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m(2); intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m(2) per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for 651 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for 6460 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS

Post-transplant recurrence of steroid resistant nephrotic syndrome in children: the Italian experience

Background: Steroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss. Methods: We identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival. Results: 101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5 months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant > 9 years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft. Conclusions: Absence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence

KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection

Funding Information: This research was supported in part by Cancer Research Switzerland , Switzerland ( KFS-4091-02-2017 ); KFSP-PrecisionMS and HMZ ImmunoTargET of the University of Zurich , Switzerland; the Cancer Research Center Zurich , Switzerland; the Vontobel Foundation , Switzerland; the Baugarten Foundation , Switzerland; the Sobek Foundation , Germany; the Swiss Vaccine Research Institute , Switzerland; Roche , Switzerland; Novartis , Switzerland; and the Swiss National Science Foundation , Switzerland ( 310030B_182827 and CRSII5_180323 ). A.M.M. was funded by a National Institutes of Health , United States, grant ( R01 CA189806 ). N.C. was supported by a career advancement grant from the University of Zurich , Switzerland ( FK-18-026 ). D.M. and M.B. were supported by MD-PhD fellowships from the Swiss National Science Foundation , Switzerland, and the Swiss Academy of Medical Sciences , Switzerland ( 323530_145247 and 323630_19938 ).Peer reviewedPublisher PD