RESUMO
Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19-2.25]), 26 months (1.20 [95% CI 0.48-1.91]), and 38 months (1.52 [95% CI 0.74-2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43-1.07]), 26 months (mean difference 0.65 [95% CI 0.27-1.03]), and 38 months (mean difference 0.72 [95% CI 0.25-1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34-43.38]), 26 months (mean difference 29.26 m [95% CI 14.87-43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32-54.09]). No new safety signals were identified. Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding: Financial support for the registry from Biogen, Novartis and Roche.
RESUMO
In phytopathology quantitative measurements are rarely used to assess crop plant disease symptoms. Instead, a qualitative valuation by eye is often the method of choice. In order to close the gap between subjective human inspection and objective quantitative results, the development of an automated analysis system that is capable of recognizing and characterizing the growth patterns of fungal hyphae in micrograph images was developed. This system should enable the efficient screening of different host-pathogen combinations (e.g., barley-Blumeria graminis, barley-Rhynchosporium secalis) using different microscopy technologies (e.g., bright field, fluorescence). An image segmentation algorithm was developed for gray-scale image data that achieved good results with several microscope imaging protocols. Furthermore, adaptability towards different host-pathogen systems was obtained by using a classification that is based on a genetic algorithm. The developed software system was named HyphArea, since the quantification of the area covered by a hyphal colony is the basic task and prerequisite for all further morphological and statistical analyses in this context. By means of a typical use case the utilization and basic properties of HyphArea could be demonstrated. It was possible to detect statistically significant differences between the growth of an R. secalis wild-type strain and a virulence mutant.