Teresa Nguyen, Steve McKerral, Phil Bergeron, Brian Safina, Dan Sutherlin. "United States Patent WO2017058821 Therapeutic Compounds and Methods Use Thereof", Jun 4, 2017
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The objective of this study is to characterize changes in hemodynamics, pain, and anxiety during office-based endoscopic sinus procedures performed under local anesthesia.We conducted a prospective study of adults undergoing in-office endoscopic sinus procedures under local anesthesia. Patients with American Society of Anesthesiologists (ASA) Physical Status Classification System class 1 or 2 were included. Anesthesia was administered by topical 4% lidocaine/oxymetazoline and submucosal injection of 1% lidocaine/1:200,000 epinephrine. Vital signs and pain were measured at baseline, postinjection, and 5-minute intervals throughout the procedure. Anxiety levels were scored using the State-Trait Anxiety Inventory (STAI). Univariate and multivariate regression analyses were performed to identify factors significantly associated with changes in each hemodynamic metric.Twenty-five patients were studied. This cohort was 52% male, mean age of 57.8 ± 14.4 years, and Charlson Comorbidity Index (CCI) median of 2. Mean procedure duration was 25.0 ± 10.3 minutes. Mean maximal increase in systolic blood pressure (SBP) was 24.6 ± 17.8 mmHg from baseline. Mean maximal heart rate increase was 22.8 ± 10.8 beats per minute (bpm) from baseline. In multivariate regression analysis, when accounting for patient age, cardiac comorbidity, CCI, and ASA, older age was significantly associated with an increase of >20 mmHg in SBP (p = 0.043). Mean pain score during procedures was 1.5 ± 1.3 with a mean maximum of 4.0 ± 2.6. STAI anxiety scores did not change significantly from preprocedure to postprocedure (32.8 ± 11.6 to 31.0 ± 12.6, p = 0.46). No medical complications occurred.Although patients appear to tolerate office procedures well, providers should recognize the potential for significant fluctuations in blood pressure during the procedure, especially in older patients.
View details for DOI 10.1002/alr.22460
View details for PubMedID 31899857
Using structure- and ligand-based design principles, a novel series of piperidyl chromane arylsulfonamide Nav1.7 inhibitors was discovered. Early optimization focused on improvement of potency through refinement of the low energy ligand conformation and mitigation of high in vivo clearance. An in vitro hepatotoxicity hazard was identified and resolved through optimization of lipophilicity and lipophilic ligand efficiency to arrive at GNE-616 (24), a highly potent, metabolically stable, subtype selective inhibitor of Nav1.7. Compound 24 showed a robust PK/PD response in a Nav1.7-dependent mouse model, and site-directed mutagenesis was used to identify residues critical for the isoform selectivity profile of 24.
View details for DOI 10.1021/acs.jmedchem.9b00141
View details for PubMedID 30943032
Currently, Achilles tendon rupture repair is surgically addressed with an open or minimally invasive approach using a heavy, nonabsorbable suture in a locking stitch configuration. However, these sutures have low stiffness and a propensity to stretch, which can result in gapping at the repair site. Our study compares a new multifilament stainless steel cable-crimp repair method to a standard Krackow repair using multistrand, ultra-high molecular weight polyethylene polyester sutures. Eight matched pairs of cadavers were randomly assigned for Achilles tendon repair using either Krackow technique with polyethylene polyester sutures or the multifilament stainless steel cable-crimp technique. Each repair was cyclically loaded from 10 to 50 N for 100 loading cycles, followed by a linear increase in load until complete failure of the repair. During cyclic loading, 4 of the 8 Krackow polyethylene polyester suture repairs failed, whereas none of the multifilament stainless steel cable crimp repairs failed. Load to failure was greater for the multifilament stainless steel cable crimp repairs (321.03 ± 118.71 N) than for the Krackow polyethylene polyester suture repairs (132.47 ± 103.39 N, p?=?.0078). The ultimate tensile strength of the multifilament stainless steel cable crimp repairs was also greater than that of the Krackow polyethylene polyester suture repairs (485.69 ± 47.93 N vs 378.71 ± 107.23 N, respectively, p?=?.12). The mode of failure was by suture breakage at the crimp for all cable-crimp repairs and by suture breakage at the knot, within the tendon, or suture pullout for the polyethylene polyester suture repairs. The multifilament stainless steel cable crimp construct may be a better alternative for Achilles tendon rupture repairs.
View details for DOI 10.1053/j.jfas.2019.01.022
View details for PubMedID 31882153