(2012) Multicenter results of stereotactic body radiotherapy (SBRT) for non-resectable primary liver tumors, Acta Oncologica, 51:5, 575-583,

The authors report a case of very late reactivation of retinopathy of prematurity (ROP) after bevacizumab monotherapy. A female born at 630 g and 24 weeks received two bilateral treatment of bevacizumab (Avastin; Genentech, South San Francisco, CA) for aggressive posterior ROP (APROP). At 2.5 years of age, ROP reactivated in the form of tractional retinal detachment in one eye and milder reactivation in the other. Although intravitreal bevacizumab treatment is effective in inducing regression of ROP, late reactivation and retinal detachments can occur after initial extended quiescence. Due to alterations of disease progression after bevacizumab, close follow-up by peripheral fluorescein angiography and laser ablation of persistent avascular retina is recommended to prevent disease reactivation and progression to retinal detachment.

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass<2.3kg (5 lb.), resistance artery endothelial function, assessed by forearm blood flow to brachial artery infusion of acetylcholine (FBFACh), increased ∼30% with trehalose (13.3±1.0 vs. 10.5±1.1 AUC, P=0.02), but not maltose (P=0.40). This improvement in FBFACh was abolished when endothelial nitric oxide (NO) production was inhibited. Endothelium-independent dilation, assessed by FBF to sodium nitroprusside (FBFSNP), also increased ∼30% with trehalose (155±13 vs. 116±12 AUC, P=0.03) but not maltose (P=0.92). Changes in FBFACh and FBFSNP with trehalose were not significant when subjects with Δbody mass≥2.3kg were included. Trehalose supplementation had no effect on conduit artery endothelial function, large elastic artery stiffness or circulating markers of oxidative stress or inflammation (all P>0.1) independent of changes in body weight. Our findings demonstrate that oral trehalose improves resistance artery (microvascular) function, a major risk factor for cardiovascular diseases, in MA/O adults, possibly through increasing NO bioavailability and smooth muscle sensitivity to NO.

In our study, bevacizumab-treated eyes with APROP have a higher likelihood of recurrence and larger area of persistent nonperfusion than in eyes with CROP. Treatment of ROP with bevacizumab followed by prophylactic laser has a low rate of unfavorable structural outcome.

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