Impact of Zika virus on the human type I interferon osteoimmune response.

BACKGROUND: The developing field of osteoimmunology supports importance of an interferon (IFN) response pathway in osteoblasts. Clarifying osteoblast-IFN interactions is important because IFN is used as salvage anti-tumor therapy but systemic toxicity is high with variable clinical results. In addition, osteoblast response to systemic bursts and disruptions of IFN pathways induced by viral infection may influence bone remodeling. ZIKA virus (ZIKV) infection impacts bone development in humans and IFN response in vitro. Consistently, initial evidence of permissivity to ZIKV has been reported in human osteoblasts. HYPOTHESIS: Osteoblast-like Saos-2 cells are permissive to ZIKV and responsive to IFN. METHODS: Multiple approaches were used to assess whether Saos-2 cells are permissive to ZIKV infection and exhibit IFN-mediated ZIKV suppression. Proteomic methods were used to evaluate impact of ZIKV and IFN on Saos-2 cells. RESULTS: Evidence is presented confirming Saos-2 cells are permissive to ZIKV and support IFN-mediated suppression of ZIKV. ZIKV and IFN differentially impact the Saos-2 proteome, exemplified by HELZ2 protein which is upregulated by IFN but non responsive to ZIKV. Both ZIKV and IFN suppress proteins associated with microcephaly/pseudo-TORCH syndrome (BI1, KI20A and UBP18), and ZIKV induces potential entry factor PLVAP. CONCLUSIONS: Transient ZIKV infection influences osteoimmune state, and IFN and ZIKV activate distinct proteomes in Saos-2 cells, which could inform therapeutic, engineered, disruptions.

Nephron-sparing surgery for Wilms tumor: A systematic review.

INTRODUCTION: Radical nephrectomy (RN, or total nephrectomy) is the current gold-standard surgical treatment for children with Wilms tumors (WT). However, nephron-sparing surgery (NSS, or partial nephrectomy) has recently been gaining increasing attention. The objective of this systematic review is to compare the effectiveness of NSS as compared with RN for the treatment of children with WT. METHODS: We searched the Cochrane Controlled Trials Register, clinicaltrials.gov, MEDLINE, EMBASE, Google Scholar, and recently presented meeting abstracts for reports in English. The bibliographies of included studies were then hand-searched for any missed articles. The protocol was prospectively registered. Manuscripts were assessed and data abstracted in duplicate with differences resolved by the senior author. Owing to high heterogeneity among the final included studies, only a qualitative systematic review was performed; no formal meta-analysis was undertaken. RESULTS: We identified 694 articles, 118 of which were selected for full-text review and 66 of which were included in the final analysis. Most studies were single- or multi-institution retrospective case series (60, 91%), with a small number of prospective cohort studies (6, 9%) and 1 administrative database analysis. Most studies were from Europe (27, 41%) or North America (21, 32%). Nearly half (32, 48%) of studies those were included were dated from 2010 or later. In total, data on 4,002 patients were included, of whom 1,040 (26%) underwent NSS and 2,962 (74%) underwent NSS. Reported rupture rates were similar between RN and NSS (13% vs. 7%), as were recurrence rates (12% vs. 11%) and survival rates (85% vs. 88%). However, these comparisons are limited by inherent biases in the design and reporting of most included studies. CONCLUSIONS: Most contemporary studies reporting the use of NSS in children with WT report similar long-term outcomes to RN. However, most existing studies are limited by their small numbers, inconsistent reporting, and methodological biases. There are significant opportunities for future research on the use of NSS in children with WT, including issues related to surgical quality, optimal technique, timing and duration of chemotherapy, and variation in the use of NSS among centers.