BACKGROUND AND OBJECTIVES: Historically, autosomal recessive 5q-linked spinal muscular atrophy (SMA) has been the leading inherited cause of infant death. SMA is caused by the absence of the SMN1 gene, and SMN1 gene replacement therapy, onasemnogene abeparvovec-xioi, was Food and Drug Administration approved in May 2019. Approval included all children with SMA age ,2 years without end-stage weakness. However, gene transfer with onasemnogene abeparvovec-xioi has been only studied in children age #8 months. METHODS:In this article, we report key safety and early outcome data from the first 21 children (age 1-23 months) treated in the state of Ohio.RESULTS: In children #6 months, gene transfer was well tolerated. In this young group, serum transaminase (aspartate aminotransferase and alanine aminotransferase) elevations were modest and not associated with g glutamyl transpeptidase elevations. Initial prednisolone administration matched that given in the clinical trials. In older children, elevations in aspartate aminotransferase, alanine aminotransferase and g glutamyl transpeptidase were more common and required a higher dose of prednisolone, but all were without clinical symptoms. Nineteen of 21 (90%) children experienced an asymptomatic drop in platelets in the first week after treatment that recovered without intervention. Of the 19 children with repeated outcome assessments, 11% (n = 2) experienced stabilization and 89% (n = 17) experienced improvement in motor function. CONCLUSIONS:In this population, with thorough screening and careful post-gene transfer management, replacement therapy with onasemnogene abeparvovec-xioi is safe and shows promise for early efficacy.

Background Segmental bone loss remains a challenging clinical problem. A frequent mitigating factor is inadequate blood supply. Small molecules that activate the hypoxia inducible factor pathway (HIF) can be used to stimulate angiogenesis. We investigated an approach to promote healing using angiogenic and osteogenic compounds in combination with a biodegradable, weight bearing scaffold. Methods Adult rats underwent removal of a 5mm segment of femur stabilized by a cylindrical biodegradable implant and intramedullary fixation. Treatment groups included (1) saline (negative control), (2) desferrioxamine ((DFO), a HIF activator), (3) low dose rhBMP-2 (5µg), (4) DFO and low dose rhBMP-2 (5µg) or (5) rh-BMP-2 (10µg). Angiography was used to evaluate vascularity. Bone healing was assessed by radiographs, µCT, histology and biomechanical testing. Results Increased vascularity was seen at 6 weeks in the DFO treatment group. There appeared to be increased bone bridging as assessed by radiographic scores and µCT in the BMP groups, although the quantification of bone volume did not show statistically significant differences. Biomechanical testing revealed improved stiffness in the treatment groups. Conclusions DFO improved angiogenesis and stiffness of bone healing in segmental defects. BMP improved radiographic scores and stiffness. Use of angiogenic compounds in segmental bone loss is promising. Clinical Relevance Activation of the HIF pathway may prove useful for bone defects, particularly where impaired blood supply exists. The low cost approach could be useful in segmental bone defects clinically.

Melatonin was measured over 24 hr in the eyestalks of Uca pugilator by means of radioimmunoassay; crabs were acclimatized either to a LD 12:12 photoperiod or constant darkness. A significant peak occurred at 13.00 hr in the LD 12:12 crabs. A photophase peak in melatonin has only been reported in one other species, also a crustacean. In constant darkness, two melatonin peaks occurred, one at 16.00 hr and the other 12 hr later; these results suggest that the melatonin cycle is a true circadian rhythm. HPLC with ultraviolet-visible detection was used to confirm the identity of melatonin immunoactivity. The influence of melatonin on regeneration of the walking legs was also examined: eyestalks were either removed or left intact, and limb bud length was measured every other day for at least 17 days in control and melatonin-treated crabs (60 microg ml(-1) seawater). Melatonin significantly increased the rate of limb regeneration in both eyestalk-intact and eyestalk-removed groups; this is contrary to results of regeneration studies in other phyla, in which similar melatonin concentrations inhibited regeneration.

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BACKGROUND AND OBJECTIVE: Retinovascular anomalies in the fellow eyes of patients with Coats’ disease have been described, but the clinical significance is unknown, as well as whether these lesions progress over time. PATIENTS AND METHODS: This is an international, multi center, retrospective, observational cohort study of fellow-eye abnormalities on widefield fluorescein angiography in patients with Coats’ disease. RESULTS: Three hundred fifty eyes of 175 patients with Coats’ disease were analyzed. A total of 33 patients (18.8%) demonstrated abnormal fellow-eye findings: 14 (42.4%) telangiectasias, 18 (54.5%) aneurysms, six (18.2%) segmental non-perfusion, six (18.2%) leakage, and two (6.0%) vascular tortuosity. All eyes were asymptomatic, and none of the lesions progressed over time. There was no association between fellow-eye findings with severity of Coats’ disease (P = .16), patient age (P = .16), or presence of systemic vascular disease (P = .16). CONCLUSIONS: The vascular abnormalities in fellow eyes of patients with Coats’ disease did not progress over time. Observation is a reasonable initial management strategy.

Background The prevalence of disabilities is rising steadily, reflecting an aging population and an increasing burden of chronic conditions affecting quality of life. There are scant national data on the prevalence of disability among individuals with chronic obstructive pulmonary disease (COPD). The main objective was to estimate the prevalence of common disabilities among US-based individuals diagnosed with COPD. Methods Data from the BRFSS, a national telephone survey examining health-related behaviors in 2016-2017 were analyzed. The study population consisted of individuals with self-reported COPD (N = 38352 in 2016 and N = 35423 in 2017). The prevalence of disabilities in hearing, vision, cognition, mobility, and independent living were obtained and adjusted with sampling weights. Healthcare access measures were described by type of disability. Results Mobility disability had the highest prevalence of 45.9 (44.8-47.0) % in 2016 and 48.4 (47.3-49.5) % in 2017 among respondents with COPD. The prevalence of disabilities was highest among those 45-64 years old, except for hearing and cognition. Hearing disabilities were most prevalent among males with COPD while cognitive and mobility disabilities were most prevalent among females with COPD. While differences in the prevalence of disabilities were observed, access to health care was similar by disability type and age group among respondents. Conclusion Contrary to expectation, the highest prevalence of disabilities was found not to be among those 65 years old and above. Further research is needed to explain this age-specific shift in

Social media has become a part of everyday life. It has changed the way we obtain and distribute information, connect, and interact with others. As the number of platforms and users grow, medical professionals have learned the value social media can have in education, research, advocacy, and clinical care initiatives. Platforms provide opportunities to network, build collaborations, and develop a reputation. This is part one of a two-part series. This article provides an overview on how social media can benefit professional career development for clinicians and researchers, as well as for advocacy to raise awareness against biases, disparities, and for patient benefit. We review challenges, limitations, and best practices for social media use by medical professionals with neurology-specific examples.

Risk, III.