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.

Hypoglycemic and hypolipidemic effects of Garcinia cambogia extracts in streptozotocin-nicotinamide induced diabetic rat model.

BACKGROUND AND OBJECTIVES: Diabetes mellitus, a global health problem, is associated with metabolic complications such as hyperglycemia, hyperlipidemia, hypertension, cardiovascular diseases, and loss of vision. The present study evaluated the antidiabetic and antihyperlipidemic effects of ethanol extract of Garcinia cambogia (L.) N. Robson (G. cambogia) fruit rind in a streptozotocin-nicotinamide induced diabetic Wistar Rat model. MATERIALS AND METHODS: Streptozotocin-nicotinamide was injected intraperitoneally to induce diabetes in Wistar rats. Five groups of rats (n=6) - normal control, diabetic, diabetic treated with G. cambogia at 400 mg/kg and 800 mg/kg body weight, and diabetic treated with metformin at 500 mg/kg body weight, were studied. Blood samples were collected after three weeks of treatment. Random blood glucose (RBG), Serum total cholesterol levels (TCL), serum total triglyceride levels (TGL), high-density lipoprotein levels, and body weight were measured. RESULTS: Although G. cambogia treatment did not have any antidiabetic activity (p>0.05) rind in the streptozotocin-nicotinamide induced diabetic Wistar Rat model, it decreased the serum TCL, and body weight significantly (P<0.05). CONCLUSIONS: Ethanolic extract of G. cambogia fruit rind possesses anti-obesity activity and significantly reduces total cholesterol but does not have antidiabetic activity.

Isolation and Characterization of an Unknown Chrysosporium sp. Producing Subcutaneous Mycosis in an Immunocompromised Patient.

We report a case of subcutaneous fungal abscess over the great toe caused by a keratinophilic fungus, an unknown Chrysosporium sp., in a 60-year-old diabetic female who was treated successfully with oral fluconazole. The fungus was isolated from aspirated pus, and septate hyphae were seen in fine needle aspiration cytology. Ovoid- to club-shaped hyaline one-celled conidia (aleuriconidia) with broad truncated bases were seen, and sequencing of ITS1-5.8S-ITS2 rDNA revealed belonging to the order Onygenales and most closely related to Chrysosporium spp. isolated from a fowl. Of the 65 species within the genus Chrysosporium, very few have been reported as pathogenic.

Human dirofilariasis: an emerging zoonosis in India.

Human dirofilariasis is an uncommon zoonotic infection having a widespread geographical distribution. World over 800 cases of Dirofilaria are on record with highest numbers from Italy, Sri Lanka and republics of the ex-Soviet Union. Dirofilaria repens belongs to the subgenus Nochtiella and is the most common species identified in India. Topographically, the orbital/periorbital regions are the most common regions involved by Dirofilaria. We present a brief review of cases from India including two received in our own institute. This review focuses on the epidemiology of the disease including its geographical distribution and the probable causation of the recent increase in its incidence in Indian subcontinent.

Fetus in bladder.

This is the first reported case of vesicouterine fistula presenting with a fully formed dead fetus in the urinary bladder.

Dislodged dormia basket.

This is the first reported case of a Dormia basket being dislodged outside the ureter into the retroperitoneum during intracorporeal lithotripsy.

Amniotic band syndrome.

Amniotic band syndrome is an uncommon congenital disorder without any genetic or hereditary disposition. It involves fetal entrapment in strands of amniotic tissue and causes an array of deletions and deformations. Primary treatment is plastic and reconstructive surgery after birth with in utero fetal surgery also coming in vogue.

Congenital giant hydroureter presenting as abdominal mass in an infant.

Herein we present a case of a 7-month-old baby girl, with left single system ectopic ureter, in whom the ureter was dilated to such an extent that it presented as an abdominal mass. Diagnosis was established by means of computed tomography. Work up was completed with renal scan and micturating cystourethrography. The patient was operated and left nephorureterectomy was performed. Hydroureter has to be considered in differential diagnosis of abdominal mass in an infant.

Double whammy - mediastinal and ovarian teratoma: a rare clinical co-existence.

Teratomas are germ cell tumours arising as the result of abnormal development of totipotential cells. They are commonly encountered in the gonads and occasionally found in mediastinum. We report a case of asymptomatic 28 years old lady with concomitant mature cystic teratoma in her mediastinum and left ovary which was diagnosed incidentally during health check up. This case is reported because of its rare and unusual coexistence.

A Comparative Study on Fine Needle Aspiration Cytology versus Fine Needle Capillary Cytology in Thyroid Nodules.

OBJECTIVES: Fine needle aspiration cytology (FNAC/FNA) is the primary investigation for thyroid nodules. Fine needle capillary cytology (FNCC/FNC) is an alternative technique not commonly used, though it is easy to perform. Both the techniques have their own advantages and disadvantages. This study aims to compare these two cytological techniques for better specimen and cytological diagnosis. METHODS: This prospective study was conducted on 50 patients attending the FR Muller Medical College Hospital from May 2006 to April 2008. The patients with thyroid nodules (diagnosed by palpation) were subjected to both the cytological techniques; FNA and FNC. The specimen and results were compared and then correlated with the final histopathological findings wherever surgical specimens were available (38 cases). RESULTS: The mean age of the patients was 39.16 with a female predominance. The majority of cases were diagnosed to have nodular goiters. The FNC technique yielded 88% diagnostic superiority and adequate specimens compared to 94% by FNA. Sensitivity was 50% for FNC and 100% for FNA while specificity was 100% for both techniques; accuracy score was 97.4% for FNC and 100% for FNA in predicting malignancy. While sensitivity was 75% for FNC and 100% for FNA; specificity was 100% for both techniques, and accuracy score was 97.4% for FNC and 100% for FNA in the prediction of neoplasia. CONCLUSION: The results indicated that there was no significant difference between the two techniques; if done in tandem can give better and accurate cytological diagnosis. In highly cellular lesions, in which abundant material was obtained, FNC was more likely to be diagnostically superior, but FNA can diagnose most of the lesions. In less cellular lesions, FNA is more likely to be diagnostically superior to FNC.