Topical Esmolol Hydrochloride as a Novel Treatment Modality for Diabetic Foot Ulcers: A Phase 3 Randomized Clinical Trial.

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.

Air within surgical arterial graft on computed tomography-An alarming finding of a rare complication.

We present a case of a 61 years old lady operated 2 years back for severe superior mesenteric artery stenosis with a surgical vascular graft and presenting as acute severe abdominal pain and vomiting. Her CT angiography showed occlusion of the surgical vascular graft with graft migration into small bowel. Both the findings of graft occlusion and bowel perforation were optimally demonstrated on the CT angiography study. The alarm of bowel perforation in addition to graft infection was raised by the presence of air pockets within the graft and its communication with bowel lumen. Coexistent graft infection was evident on graft culture.

Laparoscopic splenectomy for haemangioma of the spleen.

Splenic haemangioma is a rare disorder but remains the most common benign neoplasm of the spleen. It accounts for 0.1 to 14% of many large autopsy series. Most haemangiomas tend to be discovered in adults in the age group 30-50 years. In 80% of cases splenic haemangioma is usually found incidentally. Spontaneous rupture has been reported to occur in as many as 25% of these patients especially when the diameter of the tumour is more than 4 cm necessitating splenectomy as the only modality of treatment. We report a case of splenic haemangioma in a 23-year female. Laparoscopic splenectomy was undertaken and spleen removed through a small left inguinal hand port incision. Post-operative period was uneventful and histopathological examination report showed splenic haemangioma. She remains well three years post-operative.

Megalourethra with calculi.

Megalourethra is a rare congenital malformation of the urethra. Multiple associated anomalies have been noted in the cases reported thus far. However, none of the cases reported showed associated calculi either in the megalourethra or elsewhere in the urinary tract. A case of scaphoid megalourethra is presented here to illustrate the unique presence of multiple calculi in the megalourethra.

Jejunogastric intussusception presenting with outlet obstruction.

A 77-year-old man presented with sudden-onset epigastric pain and bilious vomiting following a light breakfast. Vagotomy and gastrojejunostomy for bleeding duodenal ulcer had been done 22 years ago. Barium meal study suggested jejunogastric intussusception. At laparotomy, a retrograde type II jejunogastric intussusception was confirmed and managed by reduction of the intussusception, disconnection of gastrojejunostomy and resection of the jejunum. Postoperative recovery was uneventful.

Pelviureteric junction obstruction in duplex system.

An unusual case of a PUJ obstruction in the upper moiety of a duplex kidney is presented. PUG obstruction in duplex moieties is commonly seen in the lower moiety ureter and is usually due to extrinsic compression by a crossing vessel. In our case there was a long stenotic segment of the ureter draining a functionally insignificant and infected segment of the kidney. The opposite kidney was hypoplastic and non functional. An upper polar hemi nephrectomy was performed.