BACKGROUND: Till now, no meta-analysis is available to address the clinical profile, risk factors, different interventions, and outcomes among COVID-19–associated rhino-orbito-cerebral mucormycosis (C-ROCM) cases. MATERIALS AND METHODS: Eight literature databases were screened using appropriate keywords from November 1, 2019, to June 30, 2021. The objectives were to analyze the clinical and microbiological profile, risk factor/comorbidity, intervention, and outcome. “R-metafor package” was used for analysis. RESULTS: A total of 23 studies were included. The mean age of presentation of C-ROCM was 54.6 years. The most common presentation was ptosis (72.7%), lid edema (60.6%), proptosis (60.6%), ophthalmoplegia (57.3%), loss of vision (53.7%), facial edema (34.7%), and nasal-blockage (11.8%). Evidence of intracranial spread was seen in 42.8% of cases. Rhizopus was the most common fungus (57.1%) isolated in fungal culture. Among C-ROCM patients, diabetes was the commonest comorbid condition, and the use of corticosteroids related to COVID-19 treatment was the most common risk factor (85.75%). Compared to controlled diabetics, C-ROCM was significantly higher among uncontrolled diabetics (odds ratio [OR] 0.15, 95% confidence interval [C.I.] 0.041–0.544, P = 0.0010). However, no significant association was seen between C-ROCM and COVID-19 severity (OR 0.930, 95% C.I. 0.212–4.087, P = 0.923). For treatment, amphotericin-B was the most common antifungal drug used which was followed by surgical options. However, mortality was high (prevalence 0.344, 95% C.I. 0.205–0.403) despite treatment. CONCLUSION: Although local rhino-orbito symptoms were the first to appear, rapid intracranial extension was seen in a significant number of C-ROCM cases. Uncontrolled diabetes and excessive use of corticosteroid were the most common risk factors present among the C-ROCM cases. High index clinical suspicion is imperative (specifically among COVID-19 patients with diabetes), and routine screening may be helpful.

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INTRODUCTION: Phyllanthus niruri, a traditional herbal medicine, was found to be hepatoprotective as evidenced by several preclinical and clinical studies. However, to the best of our knowledge, there are no clinical trials available to date to evaluate its efficacy in alcoholic hepatitis. MATERIALS AND METHODS: The present study is a block randomized, double-blind, parallel-arm placebo-controlled trial that was designed to assess the efficacy of P. niruri on the liver and renal function parameters, total oxidant and antioxidant levels in alcoholic hepatitis patients in comparison to placebo over a 4-week period. Patients were screened by CAGE questionnaire, and those with a confirmed diagnosis of mild–moderate alcoholic hepatitis based on laboratory findings and Maddrey's discriminant function score were randomly allocated to treatment and placebo arms. Clinical assessments were done at baseline, 2 weeks, and 4 weeks. A total of 454 patients were screened and 100 eligible patients were recruited for the study, and 71 were analyzed using the modified intention-to-treat approach. RESULTS: Serum levels of liver and renal function parameters failed to demonstrate significant improvement with P. niruri. However, there was a statistically significant increase in the level of total antioxidants with P. niruri (P = 0.034) with an additional appetite stimulant activity (P = 0.03) in 4 weeks. CONCLUSION: A 4-week administration of P. niruri in mild–moderate alcoholic hepatitis patients showed an improvement in the total antioxidant levels with an appetite stimulant activity compared to a placebo.

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OBJECTIVE: Stress exacerbates the pathophysiology of major neurodegenerative disorders. In this study, the zebrafish (Danio rerio), the frequently used model for experimental studies of stress and other central nervous system disorders, was used to evaluate the anxiolytic potential of flavonoids, namely silibinin and naringenin on alleviating acute stress-induced anxiety. MATERIALS AND METHODS: A molecular docking study with Molegro Virtual Docker software was done to assess the binding potential of flavonoids on serotonin and dopamine receptors. To determine the bioactivity and investigate the toxicity of the flavonoids, silibinin, and naringenin, brine shrimp lethality assay, and an acute toxicity study was conducted according to Organization for Economic Co-operation and Development (OECD) Test Guideline 203. The effect of silibinin and naringenin was assessed using behavioral tasks such as the novel tank assay and the light-dark test on the zebrafish model of acute stress. RESULTS: Molecular docking studies showed a higher affinity of silibinin and naringenin for the serotonin and dopamine receptors. In comparison to the LC₅₀ value, 13.15 μg/ml of the reference standard potassium dichromate, silibinin, and naringenin yielded higher LC₅₀ values, 34.10 μg/ml and 91.33 μg/ml, respectively. The LC₅₀ value of silibinin and naringenin was observed to be >100 mg/l from the acute toxicity study on adult zebrafish. After transferring to a novel tank, silibinin and naringenin-treated zebrafish groups were found to explore the upper level of the tank, similar to standard drugs, and spent a long time in the upper level of the tank compared to the control group (p < 0.01). Both silibinin and naringenin treatment group spent increased amounts of time in the tank's illuminated part in contrast to that of the dark side as evidenced by the number of zebrafish entering or remaining in the illuminated part of the tank through the light-dark test. Silibinin and naringenin treated groups were found to spend increased time in the light side significantly on the day 15^th of evaluation as compared to the control group (p < 0.05 and p < 0.001, respectively). CONCLUSION: The flavonoids, silibinin, and naringenin were found to mitigate acute stress-induced anxiety, owing to their anxiolytic properties in the zebrafish model and may be explored as the potential therapeutic agents for treating anxiety.

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Coronavirus disease-2019 (COVID-19) is a novel viral infectious disease that the World Health Organization (WHO) has announced to be a pandemic. This meta-analysis was aimed at providing evidence for the use of ivermectin to prevent COVID-19 among hospital workers in low-resource countries. Medical databases including African Journals online, Google Scholar, PubMed, Cochrane library, EMBASE, COVID-19 research database (WHO), Clinicaltrials.gov, and SCOPUS were searched for studies on Ivermectin as a chemoprophylactic drug against COVID-19 among hospital personnel in settings with limited resources. Preprint servers such as bioRxiv and medRxiv as well as the gray literature were also searched. Studies adjudged to be eligible were identified using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses algorithm. Statistical analyses were done using Stata version 14.3. Seven studies were selected for the meta-analysis. The total sample size was 2652. There were two randomized controlled trials and five nonrandomized studies. Some studies dosed Ivermectin daily while some dosed it weekly. However, one of the studies dosed it monthly. The studies reported variable clinical benefits. I2 statistic was 92%, and random effect model was used. The pooled odd ratio was 0.11 (95% confidence interval 0.09–0.13). This implies that 89% of the participants benefited from taking Ivermectin as a form of preexposure chemoprophylaxis. Ivermectin has a significant clinical benefit as a preventive drug against COVID-19 for hospital personnel in settings with limited resources.

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OBJECTIVES: The presence of comorbidities such as cardiovascular disease, peripheral vascular disease, and chronic renal disease, or and the prevention of these ailments in diabetics, frequently demands multiple drug treatments, increasing the risk of drug-drug interactions (DDIs). The current study was focused on identifying possible DDIs on concomitant administration of losartan, a drug used to regulate hypertension along with a combination of glimepiride + metformin, widely used to treat diabetes mellitus. Possible pharmacodynamic and pharmacokinetic interactions were observed for, following single-dose as well as multiple-dose treatment protocols in normal and alloxan-induced diabetes in albino Wistar rats and rabbits. MATERIALS AND METHODS: Blood samples from surviving rats/rabbits obtained through orbital venous sinus bleeding/marginal ear vein bleeding, respectively, at predetermined intervals and put through to biochemical estimations of sugar level in the blood by Glucose oxidase/peroxidase method; insulin levels in serum using the enzyme-linked immunosorbent assay and serum glimepiride levels using the high-performance liquid chromatography. RESULTS AND DISCUSSION: Losartan, when treated as a single drug, resulted in a slight lowering of blood glucose levels in normal rats, diabetic rats and normal rabbits. Hypoglycemic activity of a combination of glimepiride + metformin was enhanced when losartan was co-administered as a single dosage schedule as well as a multiple dose schedule as indicated by a reduced blood glucose level and enhanced levels of insulin in rats as well as in rabbits. Serum glimepiride levels were also higher and pharmacokinetic parameters of glimepiride including mean residence time, C_max, T_1/2, AUMC_0-∞, AUMC_0-t, and AUC_0-∞, were significantly higher, whereas its clearance was decreased in the two regimens of losartan that was followed. CONCLUSION: It can therefore be concluded, that in diabetics with hypertension as a comorbidity condition, co-administration of losartan with glimepiride + metformin should be avoided or the dosage of a combination of glimepiride + metformin needs to be tittered to avoid recurrence of hypoglycemic episodes.

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Nicolau syndrome is a rare serious drug reaction associated with the administering various injectable medications. It is often characterized by an acute and severe pain accompanying erythema that tends to rapidly evolve into the livedoid reticular or hemorrhagic patches and less commonly to ulcers and skin necrosis. Herein, we report a 34-year-old woman who presented with painful, tender discoloration over her abdominal skin following subcutaneous glatiramer acetate injection. Since the patient was diagnosed with multiple sclerosis 18 months ago, she had been on treatment with subcutaneous glatiramer acetate injections thrice weekly. The patient was diagnosed with Nicolau syndrome clinically and histopathologically. After 15-day treatment with topical betamethasone valerate and mucopolysaccharide polysulfate cream twice daily, the lesion completely regressed with only minimal hypopigmented irregular scarring. Nicolau syndrome should be considered in patients with severe pain, tenderness, and redness localized at the injection site following glatiramer subacetate.

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INTRODUCTION: The use of glucocorticosteroids (GCs) through oral, intravenous, intramuscular, or rectal routes is prohibited in sports. Its use is permitted through inhalation, topical and intra-articular route of administration. Methylprednisolone (MP) is available for use by different routes for anti-inflammatory and immunosuppressive purposes. To discriminate its intake by permitted & forbidden routes, a reporting level of 30 ng/ml is set by World Anti-Doping Agency. The aim of this study was to compare MP's excretion profile following oral & intra-articular administration & to evaluate its effect on endogenous GCs profile. MATERIALS & METHODS: The MP was administered through oral and intra-articular route to different patients & urine samples were collected up to 100 h. The urine samples were hydrolyzed, extracted, and analyzed on Liquid chromatography-mass spectrometry/MS. RESULTS: MP levels in urine exceeded the reporting limit of 30 ng/ml after oral (8 mg) and intra-articular administration (80 mg) routes. After oral intake (8 mg), MP levels exceeded the reporting level up to 24 h. However, after intra-articular injection (80 mg), the MP could be detected above the reporting level up to 80 h. CONCLUSION: The findings reveal that the MP can exceed the reporting level in urine even after administration by permitted route (i.a.). Further analysis of four endogenous GCs (Cortisol, Cortisone, TH Cortisone, and 11-deoxycortisol) showed a decreased excretion following administration of MP by oral & intra-articular routes.

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BACKGROUND: Dexmedetomidine, although an effective drug for conscious sedation during flexible bronchoscopy, has occasional side effects on the cardiovascular system which need to be addressed. MATERIALS AND METHODS: Patients between 18 and 65 years, requiring diagnostic flexible bronchoscopy, found eligible, after screening, were randomized to either receive 0.75 μg/kg intravenous dexmedetomidine over 10 min or intravenous midazolam 0.035 mg/kg over 1 min. Composite score was used as the primary outcome measure. Additional parameters recorded were: Hemodynamic variables, oxygen saturation, Ramsay sedation score, for pain intensity and distress Numerical Rating Scale, number of rescue medication doses, ease of doing bronchoscopy, Visual Analog Scale score for cough and response of the patient 24 h after bronchoscopy. RESULTS: In each group, 24 patients were enrolled. The composite score was in the ideal category in 24 patients in dexmedetomidine group and 21 in midazolam group, at nasopharynx (P = 0.234). The corresponding values at the level of trachea were 23 and 16 (P = 0.023). In dexmedetomidine group, patient response after 24 h of bronchoscopy showed quality of sedation to be excellent in 0 subjects, good in 13, fair in 9 and poor in 2 and discomfort to be nil in 7, mild 10, moderate in 7 and severe in 0. The corresponding values in midazolam group for quality of sedation were 0, 4, 14, 6, and for discomfort 0, 10, 14, 0. The Visual Analog Scale (VAS) for cough revealed a mean score of 0.800 and 1.812 (P = 0.011) during and 2.092 and 3.542 (P = 0.016) 24 h after bronchoscopy in the respective study groups. CONCLUSION: Low-dose dexmedetomidine (0.75 μg/kg single dose) appears to provide better patient comfort and equivalent safety profile when compared with midazolam.

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OBJECTIVE: The study was performed to evaluate in silico binding ability of lutein and rosmarinic acid (RA) with the envelope domain III (EDIII) proteins of the four serotypes of dengue virus (DENV), enlightening potential antiviral activity of the two compounds. MATERIALS AND METHODS: EDIII protein structures for the four DENV serotypes were retrieved from RCSB Protein data bank (PDB) and used as receptors. Four ligands of lutein and four of RA were selected from the ZINC database and used for computational molecular docking and ligand interaction analysis with the four receptors using bioinformatics tools like AutoDock Vina and Molecular Operating Environment (MOE) software. RESULTS: The EDIII of the four serotypes demonstrated significant interaction with ligands of lutein and RA. RA ligand ZINC00899870, particularly presented best binding energy values of -6.4, -7.0, and -6.9 kcal/mol with EDIII of serotype DENV-1, DENV-2, and DENV-4 respectively. Whereas, lutein ligand, ZINC14879959 presented best binding energy value of -7.9 kcal/mol for EDIII of serotype DENV-3. From the results predicted by MOE, the hydroxyl (OH) of 3, 4-dihydroxyphenyl group of RA ligand ZINC00899870 is actively involved in interaction with all four serotypes. CONCLUSION: RA is a competent candidate for further evaluation of potential in vitro antiviral activity that can be effective in conferring protection against the four serotypes of DENV.

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The current study was conducted to determine the role of C-reactive protein (CRP) and lactate dehydrogenase (LDH) as prognostic-marker and outcomes of different pharmacotherapeutic agents among patients with cerebrovascular accident (CVA). A hospital-based observational study was conducted and patients with CVA admitted were included. Serum-CRP on admission correlated positively with modified Rankin score (mRS) (r = 0.9, P < 0.001) in ischemic stroke, whereas no correlation between serum LDH with mRS (r = 0.1, P = 0.5) was observed. Neither CRP nor LDH was helpful in predicting the outcome in hemorrhagic stroke. The use of Vitamin B12 was associated with favorable outcome in ischemic CVA cases and use of folic acid was associated with favorable outcome among hemorrhagic-CVA patients.

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