Department Of Pharmacology
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Item Short- and long-term safety and efficacy of corneal collagen cross-linking in progressive keratoconus: A systematic review and m eta-analysis of randomized controlled trials(Wolters Kluwer Medknow Publications, 2022-11-25T00:00:00) Sarma, Phulen; Kaur, Hardeep; Hafezi, Farhad; Bhattacharyya, Jaimini; Kirubakaran, Richard; Prajapat, Manisha; Medhi, Bikash; Das, Kalyan; Prakash, Ajay; Singh, Ashutosh; Kumar, Subodh; Singh, Rahul; Reddy, Dibbanti; Kaur, Gurjeet; Sharma, Saurabh; Bhattacharyya, AnusuyaPURPOSE: The purpose of the study is to evaluate the safety and outcomes of corneal collagen cross-linking (CXL) and different CXL protocols in progressive keratoconus (PK) population at short and long-term. MATERIALS AND METHODS: A systematic review and meta-analysis was conducted. A total of eight literature databases were searched (up to February 15, 2022). Randomized controlled trials (RCTs) comparing CXL versus placebo/control or comparing different CXL protocols in the PK population were included. The primary objective was assessment of outcomes of CXL versus placebo and comparison of different CXL protocols in terms of maximum keratometry (Kmax) or Kmax change from baseline (?), spherical equivalent, best corrected visual acuity (BCVA), and central corneal thickness (CCT) in both at short term (6 months) and long term (1 st, 2 nd, and 3 rd year or more). The secondary objective was comparative evaluation of safety. For the meta-analysis, the RevMan5.3 software was used. RESULTS: A total of 48 RCTs were included. Compared to control, CXL was associated with improvement in ? Kmax at 1 year (4 RCTs, mean difference [MD], -1.78 [-2.71, -0.86], P = 0.0002) and 2 and 3 years (1 RCT); ?BCVA at 1 year (7 RCTs, -0.10 [-0.14, -0.06], P < 0.00001); and ? CCT at 1 year (2 RCTs) and 3 years (1 RCT). Compared to conventional CXL (C-CXL), deterioration in ? Kmax, ?BCVA and endothelial cell density was seen at long term in the transepithelial CXL (TE-CXL, chemical enhancer). Up to 2 years, there was no difference between TE-CXL using iontophoresis (T-ionto) and C-CXL. At 2 and 4 years, C-CXL performed better compared to accelerated CXL (A-CXL) in terms of improving Kmax. Although CCT was higher in the A-CXL arm at 2 years, there was no difference at 4 years. While exploring heterogeneity among studies, selection of control eye (fellow eye of the same patient vs. eye of different patient) and baseline difference in Kmax were important sources of heterogeneity. CONCLUSION: CXL outperforms placebo/control in terms of enhancing Kmax and CCT, as well as slowing disease progression over time (till 3 years). T-ionto protocol, on the other hand, performed similarly to C-CXL protocol up to 2 years. � 2023 Wolters Kluwer Medknow Publications. All rights reserved.Item COVID-19-associated rhino-orbital-cerebral mucormycosis: A systematic review, meta-analysis, and meta-regression analysis(Wolters Kluwer Medknow Publications, 2021-12-30T00:00:00) Bhattacharyya, Anusuya; Sarma, Phulen; Kaur, Hardeep; Kumar, Subodh; Bhattacharyya, Jaimini; Prajapat, Manisha; Prakash, Ajay; Sharma, Saurabh; Reddy, Dibbanti Harikrishna; Thota, Prasad; Bansal, Seema; Gautam, Bhaswati Sharma; Medhi, BikashBACKGROUND: 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. � 2021 Indian Journal of Pharmacology Published by Wolters Kluwer-Medknow.Item Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer�s disease(Springer Science and Business Media Deutschland GmbH, 2021-11-23T00:00:00) Dhapola, Rishika; Hota, Subhendu Shekhar; Sarma, Phulen; Bhattacharyya, Anusuya; Medhi, Bikash; Reddy, Dibbanti HariKrishnaAlzheimer�s disease (AD) is a major contributor of dementia leading to the degeneration of neurons in the brain with major symptoms like loss of memory and learning. Many evidences suggest the involvement of neuroinflammation in the pathology of AD. Cytokines including TNF-? and IL-6 are also found increasing the BACE1 activity and expression of NF?B resulting in generation of A? in AD brain. Following the interaction of A? with microglia and astrocytes, other inflammatory molecules also get translocated to the site of inflammation by chemotaxis and exaggerate neuroinflammation. Various pathways like NF?B, p38 MAPK, Akt/mTOR, caspase, nitric oxide and COX trigger microglia to release inflammatory cytokines. PPAR? agonists like pioglitazone increases the phagocytosis of A? and reduces inflammatory cytokine IL-1?. Celecoxib and roficoxib like selective COX-2 inhibitors also ameliorate neuroinflammation. Non-selective COX inhibitor indomethacin is also potent inhibitor of inflammatory mediators released from microglia. Mitophagy process is considered quite helpful in reducing inflammation due to microglia as it promotes the phagocytosis of over activated microglial cells and other inflammatory cells. Mitophagy induction is also beneficial in the removal of damaged mitochondria and reduction of infiltration of inflammatory molecules at the site of accumulation of the damaged mitochondria. Targeting these pathways and eventually ameliorating the activation of microglia can mitigate neuroinflammation and come out as a better therapeutic option for the treatment of Alzheimer�s disease. � 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.Item Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review(Wolters Kluwer Medknow Publications, 2021-08-18T00:00:00) Bhattacharyya, Anusuya; Sarma, Phulen; Sharma, Dibya; Das, Karuna; Kaur, Hardeep; Prajapat, Manisha; Kumar, Subodh; Bansal, Seema; Prakash, Ajay; Avti, Pramod; Thota, Prasad; Reddy, Dibbanti; Gautam, Bhaswati; Medhi, BikashSince the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-Associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment. � 2021 Wolters Kluwer Medknow Publications. All rights reserved.