Linking Ah receptor mediated effects of sediments and impacts on fish to key pollutants in the Yangtze Three Gorges Reservoir, China – A comprehensive perspective

The Three Gorges Reservoir (TGR), created in consequence of the Yangtze River's impoundment by the Three Gorges Dam, faces numerous anthropogenic impacts that challenge its unique ecosystem. Organic pollutants, particularly aryl hydrocarbon receptor (AhR) agonists, have been widely detected in the Yangtze River, but only little research was yet done on AhR-mediated activities. Hence, in order to assess effects of organic pollution, with particular focus on AhR-mediated activities, several sites in the TGR area were examined applying the "triad approach". It combines chemical analysis, in vitro, in vivo and in situ investigations to a holistic assessment. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011/2012, respectively, to identify relevant endpoints. Sediment was tested in vitro with the ethoxyresorufin-O-deethylase (EROD) induction assay, and in vivo with the Fish Embryo Toxicity Test and Sediment Contact Assay with Danio rerio. Activities of phase I (EROD) and phase II (glutathione-S-transferase) biotransformation enzymes, pollutant metabolites and histopathological alterations were studied in situ in P. vachellii. EROD induction was tested in vitro and in situ to evaluate possible relationships. Two sites, near Chongqing and Kaixian city, were identified as regional hot-spots and further investigated in 2013. The sediments induced in the in vitro/in vivo bioassays AhR-mediated activities and embryotoxic/teratogenic effects - particularly on the cardiovascular system. These endpoints could be significantly correlated to each other and respective chemical data. However, particle-bound pollutants showed only low bioavailability. The in situ investigations suggested a rather poor condition of P. vachellii, with histopathological alterations in liver and excretory kidney. Fish from Chongqing city exhibited significant hepatic EROD induction and obvious parasitic infestations. The polycyclic aromatic hydrocarbon (PAH) metabolite 1-hydroxypyrene was detected in bile of fish from all sites. All endpoints in combination with the chemical data suggest a pivotal role of PAHs in the observed ecotoxicological impacts.

A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus: The RESERVOIR Clinical Trial.

OBJECTIVES The aim of this study was to compare the efficacy of amphilimus-eluting stents (AES) with that of everolimus-eluting stents (EES) in patients with diabetes mellitus (DM). BACKGROUND The AES is a polymer-free drug-eluting stent that elutes sirolimus formulated with an amphiphilic carrier from laser-dug wells. This technology could be associated with a high efficacy in patients with DM. METHODS This was a multicenter, randomized, noninferiority trial. Patients with DM medically treated with oral glucose-lowering agents or insulin and de novo coronary lesions were randomized in a 1:1 fashion to AES or EES. The primary endpoint was the neointimal (NI) volume obstruction assessed by optical coherence tomography at 9-month follow-up. RESULTS A total of 116 lesions in 112 patients were randomized. Overall, 40% were insulin-treated patients, with a median HbA1c of 7.3% (interquartile range: 6.7% to 8.0%). The primary endpoint, NI volume obstruction, was 11.97 ± 5.94% for AES versus 16.11 ± 18.18% for EES, meeting the noninferiority criteria (p = 0.0003). Pre-specified subgroup analyses showed a significant interaction between stent type and glycemic control (p = 0.02), with a significant reduction in NI hyperplasia in the AES group in patients with the higher HbA1c (p = 0.03). By quantitative coronary angiography, in-stent late loss was 0.14 ± 0.24 for AES versus 0.24 ± 0.57 mm for EES (p = 0.27), with a larger minimal lumen diameter at follow-up for AES (p = 0.02), mainly driven by 2 cases of occlusive restenosis in the EES group. CONCLUSIONS AES are noninferior to EES for the coronary revascularization of patients with DM. These results suggest a high efficacy of the AES and may support the potential benefit of this stent in patients with DM. (A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus [RESERVOIR]; NCT01710748).

Is the sedimentation sign associated with spinal stenosis surgical treatment effect in SPORT?

STUDY DESIGN Subgroup analysis of the lumbar spinal stenosis (LSS) without degenerative spondylolisthesis diagnostic cohort of the Spine Patient Outcomes Research Trial multicenter randomized clinical trial with a concurrent observational cohort. OBJECTIVE To determine if sedimentation sign on magnetic resonance image can help with LSS treatment decisions. SUMMARY OF BACKGROUND DATA LSS is one of the most common reasons for surgery in the US elderly, but there is a dearth of reliable diagnostic tools that give a clear indication for surgery. Recent studies have suggested that positive sedimentation sign on magnetic resonance image may be a possible prognostic indicator. METHODS All patients with LSS in both the randomized and observational cohorts had imaging-confirmed stenosis, were surgical candidates, and had neurogenic claudication for at least 12 weeks prior to enrollment. Patients were categorized as "mild," "moderate," or "severe" according to stenosis severity. Of the 654 patients with LSS enrolled in Spine Patient Outcomes Research Trial, complete T2-weighted axial and sagittal digitized images of 115 patients were available for retrospective review. An independent orthopedic spine surgeon evaluated these deidentified Digital Imaging and Communications in Medicine files for the sedimentation sign. RESULTS Sixty-six percent (76/115) of patients were found to have a positive sedimentation sign. Those with a positive sedimentation sign were more likely to have stenosis at L2-L3 (33% vs. 10% P=0.016) or L3-L4 76% vs. 51%, P=0.012), and to have severe (72% vs. 33%, P<0.0001) central stenosis (93% vs. 67% P<0.001) at 2 or more concurrent levels (57% vs. 18%, P=0.01). In multivariate models, the surgical treatment effect was significantly larger in the positive sedimentation sign group for Oswestry Disability Index (-16 vs. -7; P=0.02). CONCLUSION A positive sedimentation sign was associated with a small but significantly greater surgical treatment effect for Oswestry Disability Index in patients with symptomatic LSS, after adjusting for other demographic and imaging features. These findings suggest that positive sedimentation sign may potentially be a useful adjunct to help guide an informed treatment choice regarding surgery for LSS. LEVEL OF EVIDENCE 2.