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Background ADV (adenovirus) is an important cause of viral mortality in hematopoietic stem cell transplantation (HSCT). T-cell depleted (TCD) HSCT are at increased risk of viral infections. We compared the rates and outcomes of ADV viremia and disease between TCD and conventional (CONV) HSCT at our institution. Methods This was an observational study of 624 adult and pediatric recipients of myeloablative HSCT at Memorial Sloan-Kettering Cancer Center from January 1, 2006, through March 11, 2011. Viral cultures and ADV polymerase chain reaction (PCR) were ordered as clinically indicated. ADV viremia by a quantitative PCR assay was defined as ≥1 positive value ≥1,000 copies/mL or ≥2 consecutive values at any value. Competing risk regression analyses were used to identify predictors for ADV viremia. Results Eight percent TCD and 4.0% CONV were noted to have ADV viremia at 1 year after HSCT (P=.041). Among TCD, 15% of children compared with 5% of adults developed ADV viremia (P=.008). Young age (Hazard Ratio [HR] 3.0; P<.001) and acute graft-versus-host-disease (GVHD) (HR 3.2; P=.001) were risk factors for ADV viremia. ADV viremia was a predictor of mortality (HR 6.0; P<.001). ADV disease developed in 3.5% TCD and 0.4% CONV HSCT (P=.022) with attributable mortality of 27%. Among TCD, grade 2–4 GVHD was a risk factor for ADV disease (HR 13; P<.001); age was not significant. More than 90% ADV disease cases had a viral load of ≥ 10,000 copies/mL. Conclusions Rates of ADV disease were 10-fold higher in TCD compared with CONV HSCT, predominantly in patients who developed acute GVHD. The benefit of preemptive therapy for ADV viral load ≥ 10,000 copies/mL for prevention of ADV disease in recipients of TCD grafts should be evaluated in prospective clinical trials.

Natural killer (NK) cell can inhibit tumor initiation and regulates metastatic dissemination, acting as key mediators of the innate immune response. Intrinsic factors modulating NK cells infiltration and its anticancer activity remain poorly characterized. We investigated the roles of dysregulation of micro(mi)RNAs and NK cells in progression of hepatocellular carcinoma (HCC). Methods : Small RNA sequencing were used to detect the miRNA profiles of tumor tissues from HCC patients with (n=14) or without (n=13) pulmonary metastasis and HCC cell lines with different pulmonary metastatic potentials. Chemokine expression profiling and bioinformatics were used to detect the downstream target of candidate target. In gain- and loss-of-function assays were used to investigate the role of miRNA in HCC progression. Different subsets of NK cells were isolated and used for chemotaxis and functional assays in vivo and in vitro . In situ hybridization and immunohistochemical analyses were performed to detect the expression of miRNA in tumor tissues from 242 HCC patients undergoing curative resection from 2010. Results : Three miRNAs (miR-137, miR-149-5p, and miR-561-5p) were identified to be associated with pulmonary metastasis in patients with HCC. miR-561-5p was most highly overexpressed in metastatic HCC tissues and high-metastatic-potential HCC cell lines. In gain- and loss-of-function assays in a murine model, miR-561-5p promoted tumor growth and spread to the lungs. Yet, miR-561-5p did not appear to affect cellular proliferation and migration in vitro . Bioinformatics and chemokine expression profiling identified chemokine (C-X 3 -C motif) ligand 1 (CX 3 CL1) as a potential target of miR-561-5p. Furthermore, miR-561-5p promoted tumorigenesis and metastasis via CX 3 CL1-dependent regulation of CX 3 CR1 + NK cell infiltration and function. CX 3 CR1 + NK cells demonstrated stronger in vivo anti-metastatic activity relative to CX 3 CR1 - NK cells. CX 3 CL1 stimulated chemotactic migration and cytotoxicity in CX 3 CR1 + NK cells via STAT3 signaling. Blockade of CX 3 CL1, CX 3 CR1, or of pSTAT3 signaling pathways attenuated the antitumor responses. Clinical samples exhibited a negative correlation between miR-561-5p expression and levels of CX 3 CL1 and CX 3 CR1 + NK cells. High miR-561-5p abundance, low CX 3 CL1 levels, and low numbers of CX 3 CR1 + NK cells were associated with adverse prognosis. Conclusion ...

In OSAS patients, the vessel densities in the peripapillary and parafoveal areas decreased with greater disease severity, and the decrease was more prominent in the peripapillary area.