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.

Evaluation of Interactions Between Thyroid Dysfunction in End-Stage Renal Disease Patients: A Cross-Sectional Study.

BACKGROUND: Thyroid hormones have a very crucial role in the regulation of metabolism, synthesis of proteins, development, and influencing functions of various other hormones in the human body. While both kidneys play an essential role in the metabolism of thyroid hormone by conversion of thyroxine (T4) to triiodothyronine (T3). In patients with chronic renal failure, frequent abnormal thyroid functions are observed. AIMS: To evaluate thyroid function in patients of chronic renal failure and to find out their correlation with the severity of the disease. METHODS: A total of 192 patients were selected for the study after applying inclusion and exclusion criteria. A thyroid function test was done in all enrolled subjects. Serum estimation of T3, T4, and thyroid stimulating hormone (TSH) was done by the chemiluminescent immunoassay (CLIA) method, urea was estimated by the diacetyl monoxide method (DAM, Method), and serum creatinine by Jaffe's method. The results were evaluated for age, sex, and estimated glomerular filtration rate (eGFR) of the patients in view of thyroid dysfunction. RESULTS: Of all 192 patients enrolled in the study, 124 (64.58%) were male and 68 (35.41%) were females. The observed male-to-female ratio was 1.93:1.18. The mean age of the study group (mean +/- standard deviation, SD) in males was 42+/-18 and in females 38+/-11 years (p value = 0.258). Significant reductions of serum T3, T4, and elevation of TSH were noted in both sexes. A reduced level of T3 was observed in 38.54% (42 males and 32 females) patients, reduced T4 in 34.37% (42 males and 22 females) patients, and subclinical hypothyroidism (SCH) in 16.7% (12 males and 20 females) patients. Biochemical overt hypothyroidism was noted in 7.29% (six males and eight females) of patients. CONCLUSION: Chronic renal failure is a condition of thyroid hypofunction. A higher prevalence of SCH and clinical hypothyroidism is reported here in chronic kidney disease (CKD) patients. The severity of thyroid hypofunction increases with a progressive reduction in eGFR. Hypothyroidism in CKD patients may be due to different onset mechanisms other than anti-thyroid antibodies.

Clinical-epidemiological Profile of Coronavirus Disease 19 Associated Mucomycosis (CAM) and Relation with Zinc and Iron Levels.

INTRODUCTION: Coronavirus disease associated mucormycosis (CAM), perturbed a lot by reaching to epidemic proportions particularly during the second wave of the pandemic. MATERIAL AND METHODS: This was a retrospective, observational study of patients with COVID-19-associated mucomycosis admitted in April-May 2021 at a tertiary care teaching hospital. Demographic profile, clinical and laboratory parameters were recorded Multidisciplinary treatment including antifungals and surgical interventions were noted. RESULTS: This study included 98patients of mucormycosis, diagnosed on the basis of clinical and radiological findings and later were confirmed by microbiological investigations. Out of 98 patients, 72 had rhino orbital, 24 had rhino-orbitalcerebral and 2 had pulmonary mucormycosis. Twelve had coinfection of covid 19 while 86 had developed mucormycosis within 3 weeks. CONCLUSION: CAM has posed as a continuum of challenges faced during the pandemic of covid 19. This rare and life threatening complication requires high index of suspicion for early diagnosis. Multidisciplinary involvement and timely interventions including antifungal pharmacotherapy, stringent glycemic control and surgical debridement can reduce the mortality. Mucormycosis is uniformly associated with low iron levels but role of zinc needs to be further studied.

Follow-up Study of Pulmonary Function, Exercise Capacity and Radiological Changes after Recovery from Moderate to Severe COVID Pneumonia without Mechanical Ventilation.

BACKGROUND: The long-term effects of COVID on the lungs remain unclear, but, given the extent of the pandemic, it has the potential to become a significant chronic global health problem .Aim of our study was to ascertain the proportion of patients with moderate to severe pneumonia but without mechanical ventilation who have compromised exercise capacity, pulmonary function test and presence of radiological abnormalities and to study any correlation between clinical features with radiological abnormalities. METHODS: In a hospital-based study, COVID-19 patients with moderate and severe pneumonia were followed 3 months after discharge and assessed with chest computed tomography (CT) imaging, 6 minute walk test and pulmonary function tests. RESULTS: A total of 102 participants were enrolled, including64 patients who had recovered from moderate disease and 38 patients from severe COVID-19. The patients with critical disease and who required mechanical ventilation or who had previously known chronic lung disease were excluded. High proportion of patients of both groups showed radiological abnormalities and deranged pulmonary function tests 3 months after recovery from acute illness which had significant correlation with severity of disease. CONCLUSIONS: Pulmonary function and radiological abnormalities remained in significant propotion of patients 3 months after recovery from COVID-19 that needs more attention on pulmonary rehabilitation and long term follow up of these patients.

Clinical profile of malaria at a tertiary care teaching hospital in North India.

INTRODUCTION: Despite recent reductions in the overall malaria case incidence, malaria remains an important public health issue. There has been a change in clinical and epidemiological profile of malaria in our country and vivax malaria known to be benign has been reported to cause severe complications. Therefore, the present study was conducted to delineate the clinical profile of malaria, proportion of severity, spectrum of complications, and presence of comorbidities among adult patients admitted at a tertiary health-care center in North India. MATERIALS AND METHODS: This was an observational prospective study conducted in all adult patients (>15 years of age) diagnosed to have Plasmodium vivax malaria, Plasmodium falciparum, and mixed malarial infection at a tertiary care teaching hospital on the basis of peripheral smear or rapid diagnostic tests. RESULTS: The study included 295 patients, the most common species was vivax (62%) followed by falciparum (29%) and mixed plasmodium spp. (9%). The mean age of the patients was 34.23 ± 15.7 years, with 64% male and 36% female. Out of all patients, 23% patients had at least one component of severe malaria. Severe anemia (hemoglobin <5 mg/dl), thrombocytopenia (platelet count <1 lac/cmm), and acute kidney injury were significantly greater in patients with P. vivax. Presence of comorbid conditions was observed in a significant proportion (32%) of patients. CONCLUSION: P. vivax is the plasmodium species which is responsible for most of the cases. Its potential to cause life-threatening illness is the cause of concern. The role of comorbid conditions in influencing the clinicaloutcome of malaria should be further explored.

Schwannoma in anterior mediastinum with massive pericardial effusion.

Schwannoma is a benign nerve sheath neoplasm of schwann cell origin. Mediastinum is the second most common site of schwannoma with majority originating in the posterior medistinum. Mediastinal schwannoma is slow growing and mostly asymptomatic in presentation. We present a case of schwannoma arising in the anterior mediastinum, an unusual location, complicated by massive haemorrhagic pericardial effusion. We recommend an aggressive approach in such cases with pericardiectomy to prevent reaccumulation of the pericardial fluid.