Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury.

Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin-3 (NT-3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT-3 binding and release were characterized in vitro. Then, the NT-3-loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP-coated sutures exhibited a burst release of NT-3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT-3-loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT-3-loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT-3-loaded sutures had significantly more axons per graft than rats treated with an NT-3 injection and rats without NT-3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP-coated sutures can efficiently release NT-3 to increase axonal regeneration. © 2016 Wiley Periodicals, Inc.

An Updated Approach to Antiobesity Pharmacotherapy: Moving Beyond the 5% Weight Loss Goal.

Despite professional society guidelines recommending that obesity be treated as a chronic disease by emphasizing the use of lifestyle modification in conjunction with pharmacotherapy, antiobesity medications are uncommonly prescribed in most clinical practices. The recent Food and Drug Administration approval of semaglutide 2.4 mg weekly to treat obesity-as well as other forthcoming advancements in diabetes and antiobesity medications-highlights the potential of pharmacotherapy to significantly augment weight loss efforts. In this Expert Endocrine Consult, we review the evolving role of antiobesity pharmacotherapy in clinical practice and suggest a framework for the use of these medications.

Clinician Responses to Pediatric Lipid Screens Suggestive of Severe Dyslipidemia.

Objectives: To measure case detection and response time of severe pediatric dyslipidemia, defined as non-high-density lipoprotein cholesterol (HDL-C) ≥190 mg/dL on the initial screening panel. Although low adherence to guidelines recommending universal pediatric lipid screening is well-documented, it is unknown how clinicians respond to pediatric lipid screening results suggestive of severe dyslipidemia. Study design: This study is a single-institution, retrospective review of patients 0-18 years of age with initial lipid panels completed from January 1, 2010, to June 30, 2018. A chart review was conducted on all patients with non-HDL-C ≥190 mg/dL to determine indication(s) for the initial lipid panel, specialty of ordering clinician, type of action taken to an abnormal result (repeat laboratory tests, treatment, and/or referral), time from result to clinician action, and diagnosis. Results: There were 16 860 initial lipid panels that met the inclusion criteria; 178 (1.1%) had non-HDL-C ≥190 mg/dL, indicating severe dyslipidemia. The most common indication for screening was universal screening (52%). For all lipid panels with non-HDL ≥190 mg/dL, a clinician action was documented for 47% within 7 days and 69% within 30 days. No follow-up action was documented in 18 (9%). A clinical diagnosis of familial hypercholesterolemia was the most common diagnosis, in 24% of patients. Conclusions: The majority of lipid panels with non-HDL-C ≥190 mg/dL had some action documented, although the actions varied. Universal screening was the most common indication for testing, clarifying its significance in identifying severe dyslipidemia. Further education and improved management protocols may help responses to severe dyslipidemia in children at high risk for premature cardiovascular disease.