Long-term Efficacy of Satralizumab in AQP4-IgG-Seropositive Neuromyelitis Optica Spectrum Disorder From SAkuraSky and SAkuraStar.

BACKGROUND AND OBJECTIVES: Satralizumab, an interleukin 6 receptor inhibitor, reduced the risk of protocol-defined relapse (PDR) vs placebo in 2 independent, double-blind studies in patients with neuromyelitis optica spectrum disorder (NMOSD). We assessed the long-term efficacy of satralizumab in patients with aquaporin-4-immunoglobulin G (IgG)-seropositive (AQP4-IgG+) NMOSD. METHODS: Following the double-blind periods of SAkuraSky (satralizumab + baseline immunosuppressive treatment [IST]) and SAkuraStar (satralizumab monotherapy), patients could enter the open-label extension (OLE, satralizumab 120 mg Q4W ± IST). This analysis included all AQP4-IgG+ patients who received ≥1 dose of satralizumab in the double-blind and/or OLE periods, from patients' first dose to the data cutoff (February 22, 2021). PDR in the OLE period was determined by the investigator without external adjudication. We evaluated time to first investigator-reported PDR (iPDR), severe iPDR (≥2 point increase in the Expanded Disability Status Scale [EDSS] score), and sustained EDSS worsening (EDSS score increase of ≥2, ≥1, or ≥0.5 points for patients with baseline scores of 0, 1-5, or ≥5.5, respectively, confirmed ≥24 weeks post-initial worsening), plus the annualized iPDR rate (ARR). RESULTS: Forty-six of 55 AQP4-IgG+ patients (84%) in SAkuraSky and 57/64 patients in SAkuraStar (89%) continued from the double-blind periods into the OLEs. In total, 111 AQP4-IgG+ patients received ≥1 dose of satralizumab in the double-blind and/or OLE periods and were included in these analyses (SAkuraSky: 49; SAkuraStar: 62). The median (range) duration of satralizumab exposure was 4.4 (0.1-7.0) years in SAkuraSky and 4.0 (0.1-6.0) years in SAkuraStar, with a combined 440.1 patient-years of treatment. Seventy-one of 111 patients (64%) received satralizumab for ≥192 weeks (3.7 years). At this time point, 71% (SAkuraSky) and 73% (SAkuraStar) of satralizumab-treated patients were free from iPDR, 91% (SAkuraSky) and 90% (SAkuraStar) were free from severe iPDR, and 90% (SAkuraSky) and 86% (SAkuraStar) had no sustained EDSS worsening. The overall adjusted ARR (95% CI) was 0.12 (0.08-0.18) in SAkuraSky and 0.08 (0.05-0.13) in SAkuraStar and remained stable over time. DISCUSSION: These long-term results from the OLE periods of the SAkura studies demonstrate the continued efficacy of satralizumab over more than 3.5 years of treatment. High proportions of patients remained free from relapse, severe relapse, or worsening disease, with a consistently low ARR. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov registration numbers: NCT02028884 (SAkuraSky) and NCT02073279 (SAkuraStar). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that satralizumab reduces the risk of relapse in patients with AQP4-IgG+ NMOSD beyond the first 96 weeks of treatment.

High pollutant removal efficacy of a large constructed wetland leads to receiving stream improvements.

Hewletts Creek, in Wilmington, North Carolina, drains a large suburban watershed and as such is affected by high fecal bacteria loads and periodic algal blooms from nutrient loading. During 2007, a 3.1-ha wetland was constructed to treat stormwater runoff from a 238-ha watershed within the Hewletts Creek drainage. A rain event sampling program was performed in 2009-2010 to evaluate the efficacy of the wetland in reducing pollutant loads from the stormwater runoff passing through the wetland. During the eight storms sampled, the wetland greatly moderated the hydrograph and retained and/or removed 50 to 75% of the inflowing stormwater volume. High removal rates of fecal coliform bacteria were achieved, with an average load reduction of 99% and overall concentration reduction of >90%. Particularly high (>90%) reductions of ammonium and orthophosphate loads also occurred, and lesser but still substantial reductions of total phosphorus (89%) and total suspended solids loads (88%) were achieved. Removal of nitrate was seasonally dependent, with lower removal occurring in cold weather and a high percentage (90%+) of nitrate load removal occurring in the growing season when water temperature exceeded 15°C. Long-term before-and-after sampling in downstream Hewletts Creek proper showed that, after wetland construction, statistically significant average decreases of 43% for nitrate, 72% for ammonium, and 59% for fecal coliform bacteria were realized. Wetland features contributing to the high pollutant control efficacy included available space for a large wetland, construction of deep forebays, and a dense and diverse aquatic and shoreline plant assemblage.

Bruise detection in Pacific pink salmon (Oncorhynchus gorbuscha) by visible and short-wavelength near-infrared (SW-NIR) spectroscopy (600-1100 nm).

Visible and short-wavelength near-infrared (SW-NIR) spectroscopy (600-1100 nm) was used to detect bruises in intact, whole Pacific pink salmon (Oncorhynchus gorbuscha). The measurements were performed noninvasively through the skin and scales in the diffuse reflectance mode. Digital images of bruised and nonbruised regions of fish were captured after the fish samples were filleted. Image analysis was conducted using Adobe Photoshop 7.0 with relative gray values used as reference values in a partial least-squares (PLS) model. A PLS cross-validation model using six latent variables yielded a standard error of prediction (SEP = 0.05%, R = 0.83). Approximately 84% of all nonbruised spectra were correctly classified, whereas approximately 81% of all bruised spectra were correctly classified. These results suggest that visible and SW-NIR could be used to control the bruise defect of fish products during processing, thereby improving product consistency and quality.

Pollutant removal efficacy of three wet detention ponds.

Monthly inflow and outflow data were collected from three wet detention ponds in Wilmington, North Carolina, for a 29-mo period. Two ponds drained urban areas consisting primarily of residential, mixed services, and retail usage, while the third mainly drained residential and golf course areas. One of the urban ponds achieved significant reductions in total nitrogen, nitrate, ammonium, total phosphorus, orthophosphate, and fecal coliform bacterial counts. This pond was characterized by a high length to width ratio, with most inputs directed into the upper area, and extensive coverage by a diverse community of aquatic macrophyte vegetation. The second urban pond achieved significant reductions in turbidity and fecal coliform bacterial counts, but there were no significant differences between inflowing and outflowing water nutrient concentrations. There were substantial suburban runoff inputs entering the mid- and lower-pond areas that short-circuited pollutant removal contact time. The golf course pond showed significant increases in nitrate, ammonium, total phosphorus, and orthophosphate in the outflow relative to the inflow, probably as a result of course fertilization. However, nutrient concentrations in the outflow water were low compared with discharges from a selection of other area golf courses, possibly a result of the outflow passing through a wooded wetland following pond discharge. To achieve good reduction in a variety of pollutants, wet pond design should include maximizing the contact time of inflowing water with rooted vegetation and organic sediments. This can be achieved through a physical pond design that provides a high length to width ratio, and planting of native macrophyte species.