Importance:Preclinical and phase 1/2 studies with esmolol hydrochloride suggest its potential role in treatment of diabetic foot ulcers (DFUs). Objective:To study the efficacy of topical esmolol for healing of uninfected DFUs. Design, Setting, and Participants:A randomized, double-blind, multicenter, phase 3 clinical trial was conducted from December 26, 2018, to August 19, 2020, at 27 referral centers across India. Participants included adults with DFUs. Interventions:Participants were randomized after a run-in phase (1 week) to receive esmolol, 14%, gel with standard of care (SoC), SoC only, or vehicle with SoC (3:3:1 proportion) for 12 weeks (treatment phase) and followed up subsequently until week 24. Main Outcomes and Measures:The primary outcome was the proportion of wound closure within the 12-week treatment phase in the esmolol with SoC and SoC only groups. Analysis was conducted using an intention-to-treat safety evaluable population, full analysis set or efficacy-evaluable population, and per-protocol population comparing the esmolol plus SoC and SoC only treatment groups. Results:In the study, 176 participants (122 men [69.3%]; mean [SD] age, 56.4 [9.0] years; mean [SD] hemoglobin A1c level, 8.6% [1.6%]) with DFUs classified as University of Texas Diabetic Wound Classification system grade IA and IC (mean [SD] ulcer area, 4.7 [2.9] cm2) were randomized to the 3 groups. A total of 140 participants were analyzed for efficacy. The proportion of participants in the esmolol with SoC group who achieved target ulcer closure within 12 weeks was 41 of 68 (60.3%) compared with 30 of 72 (41.7%) participants in the SoC only group (odds ratio [OR], 2.13; 95% CI, 1.08-4.17; P = .03). A total of 120 participants completed the end of study visit which were analyzed. Target ulcer closure by the end of the study (week 24) was achieved in 44 of 57 (77.2%) participants in the esmolol with SoC group and 35 of 63 (55.6%) participants in the SoC only group (OR, 2.71; 95% CI, 1.22-5.99; P = .01). The median time for ulcer closure was 85 days for the esmolol with SoC group and was not estimable for SoC only group. Significant benefits of Esmolol with SoC were seen in patients with factors that impede the healing of DFU. Treatment-emergent adverse events were noted in 18.8% of the participants, but most (87.3%) of these events were not attributable to the study drug. Conclusions and Relevance:In this multicenter, randomized, double-blind clinical trial, the addition of esmolol to SoC was shown to significantly improve the healing of DFUs. With these results, topical esmolol may be an appropriate addition to SoC for treating DFUs. Trial Registration:ClinicalTrials.gov Identifier: NCT03998436; Clinical Trial Registry, India CRI Number: CTRI/2018/11/016295.
Study Design. Cohort. Objective. To evaluate perioperative morbidity in patients undergoing minimally invasive spine surgery of the lumbar spine while continuing the antiplatelet drug (APD) perioperatively as compared with those not continuing these drugs and those not on these drugs. Summary of Background Data. While discontinuation of antiplatelet drugs carries with it the risk of thrombosis of the cardiac stents, myocardial infarction, peripheral vascular occlusion, cerebro-vascular events and other thrombotic complications, continuation of these drugs has the risk of intra spinal bleeding and the serious consequences of subsequent epidural hematoma with associated spinal cord compression. Methods. This institutional review board approved study included 1587 patients from 2011 to 2018. Perioperative parameters were analyzed for 216 patients who underwent spinal surgery after the discontinuation of anticoagulation therapy, 240 patients who continued to take APD daily through the perioperative period and 1131 patients who were never exposed to APD therapy. The operative time, intraoperative estimated blood loss, length of hospital stay, incidence of clinically evident hematoma, and transfusion of blood products were also recorded and compared in three cohorts. Results. The patients who continued taking APD in the perioperative period had a longer length of hospital stay on average (2.5 ± 0.67 vs. 1.59 ± 0.76 and 1.67 ± 0.83, P < 0.05), whereas there was no significant difference in the operative time, estimated blood loss, the amount of blood products transfused, and overall intra and postoperative complication rate. There were no instances of postoperative wound soakage or neurological deficit suggestive of possible spinal epidural hematomas in either of the study groups. Conclusion. The current study has observed no appreciable increase in perioperative morbidities including bleeding related complication rates in patients undergoing lumbar minimally invasive spine surgery while continuing to take APD compared with patients who either discontinued APD prior to surgery or those not taking APD. Level of Evidence: 4
BACKGROUND CONTEXT Facet joint violation (FV) was reported as variable iatrogenic damage that can be a crucial risk factor leading to the adjacent segment degeneration (ASD) in index open and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) performed for various lumbar degenerative indications.“Blind” screw placement technique in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) contributes to the increasing incidence of FV that can be influenced by several potential factors. Previous studies have evaluated facet joint violations in open or percutaneous screw cases, but there are no reports describing a direct institutional and single lumbar level comparison. PURPOSE Objective: To compare the incidence of superior joint facet violation for open vs percutaneous pedicle screws at a single lumbar level and to evaluate patient and surgical factors that impact this outcome. STUDY DESIGN/SETTING We prospectively analyzed 200 cases undergoing single-segment MIS-TLIF and open TLIF for degenerative lumbar spine disease with stenosis with or without spondylolisthesis. We used a CT grading system which represents progressively increasing grades of facet joint violation. Patient and surgical factors like gender, age, body mass index (BMI), top-screw level, and depth of spine were analyzed in both groups to determine their impact on facet violation. Moreover, visual analog scale (VAS), and Oswestry Disability Index (ODI) scores were assessed in both groups pre- and postoperatively. PATIENT SAMPLE Our cohort consisted of 100 open patients and 100 percutaneous cases. RESULTS Percutaneous procedures had a higher overall violation grade (p=0.018) and greater incidence of high-grade violations (p=0.0059) compared to open procedures. Bivariate analysis showed significantly greater violations in percutaneous cases for age CONCLUSIONS This study demonstrates greater facet violations for percutaneously placed pedicle screws compared to open at single-level lumbar procedures. MIS-TLIF is an effective treatment for lumbar degenerative disease, but FV occurred at a higher incidence. Facet joints should be protected in MIS-TLIF to avoid ASD. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.
