Publications by authors named "Tarun Sharma"

365 Publications

Managing paediatric giant retinal tears.

Eye (Lond) 2021 Jun 11. Epub 2021 Jun 11.

Edward S. Harkness Eye Institute, Columbia University Medical Center, New York, NY, USA.

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http://dx.doi.org/10.1038/s41433-021-01623-wDOI Listing
June 2021

The safety of phosphodiesterase-5 inhibitors in valvular heart disease.

J Cardiovasc Pharmacol 2021 May 27. Epub 2021 May 27.

Division of Cardiology, Medical College of Georgia at Augusta University.

Abstract: Erectile dysfunction is a common entity in clinical practice. Primary erectile dysfunction not related to vasculopathy or psychiatric disorder, can be readily treated with phosphodiesterase inhibitors. These drugs have many physiologic effects which can alter a patient's hemodynamic profile considerably, especially in the presence of concomitant structural heart disease, specifically valvular heart disease. While some contraindications to use of PDE5 inhibitors in patients with cardiovascular disease are defined, the effect of these drugs in presence of valvular heart disease is not well documented. The purpose of this review is to analyze the data regarding the safety of PDE5 inhibitors in patients with valvular heart disease.
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http://dx.doi.org/10.1097/FJC.0000000000001071DOI Listing
May 2021

Fluorophotometric Measurement of Corneal Autofluorescence in Diabetic and Normal Eyes.

Nepal J Ophthalmol 2020 Jul;12(24):201-208

Shri Bhagwan Mahavir Department of Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India.

Introduction: Corneal autofluorescence (AF) has been recommended as an indicator of diabetic retinopathy. This study was conducted to evaluate corneal autofluorescence in non-insulin dependent diabetes subjects (with and without diabetic retinopathy) and compare the changes with healthy subjects.

Materials And Methods: In this cross-sectional study, 145 eyes of diabetes mellitus subjects with and without diabetic retinopathy and 34 eyes of normal healthy subjects were included. Diabetic patients were subdivided by the severity of retinopathy based on international clinical diabetic retinopathy disease severity scale. The investigations included fluorophotometric determination of corneal autofluorescence, fasting glucose level (FBS) and glycosylated hemoglobin (HbA1c).

Results: The corneal autofluorescence values were significantly higher in moderate NPDR, severe NPDR and PDR when compared with healthy subjects (p<0.001). FBS values and HbA1c were significantly higher in all diabetic groups than the healthy subjects (p<0.001). In linear regression test, corneal autofluorescence seem to be related to duration of diabetes and FBS, but not with age and HbA1c.

Conclusion: We conclude that the level of corneal autofluorescence is dependent on the severity of diabetic retinopathy. Our study suggests that the formation of autofluorescent products in cornea depend upon the glucose concentration in the aqueous humor.
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http://dx.doi.org/10.3126/nepjoph.v12i2.27972DOI Listing
July 2020

Wuhan to World: The COVID-19 Pandemic.

Front Cell Infect Microbiol 2021 30;11:596201. Epub 2021 Mar 30.

Translational Health Science and Technology Institute (THSTI), Faridabad, India.

COVID-19 is a Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-2, a novel virus which belongs to the family . It was first reported in December 2019 in the Wuhan city of China and soon after, the virus and hence the disease got spread to the entire world. As of February 26, 2021, SARS-CoV-2 has infected ~112.20 million people and caused ~2.49 million deaths across the globe. Although the case fatality rate among SARS-CoV-2 patient is lower (~2.15%) than its earlier relatives, SARS-CoV (~9.5%) and MERS-CoV (~34.4%), the SARS-CoV-2 has been observed to be more infectious and caused higher morbidity and mortality worldwide. As of now, only the knowledge regarding potential transmission routes and the rapidly developed diagnostics has been guiding the world for managing the disease indicating an immediate need for a detailed understanding of the pathogen and the disease-biology. Over a very short period of time, researchers have generated a lot of information in unprecedented ways in the key areas, including viral entry into the host, dominant mutation, potential transmission routes, diagnostic targets and their detection assays, potential therapeutic targets and drug molecules for inhibiting viral entry and/or its replication in the host including cross-neutralizing antibodies and vaccine candidates that could help us to combat the ongoing COVID-19 pandemic. In the current review, we have summarized the available knowledge about the pathogen and the disease, COVID-19. We believe that this readily available knowledge base would serve as a valuable resource to the scientific and clinical community and may help in faster development of the solution to combat the disease.
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http://dx.doi.org/10.3389/fcimb.2021.596201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042280PMC
April 2021

Optical Coherence Tomography-Based Prevalence of Diabetic Macular Edema and its Associated Risk Factors in Urban South India: A Population-Based Study.

Ophthalmic Epidemiol 2021 Apr 15:1-7. Epub 2021 Apr 15.

Department of Vitreoretina, Shri Bhagwan Mahavir Vitreoretinal Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India.

: To estimate the prevalence of optical coherence tomography (OCT)-defined diabetic macular oedema (DME) in urban South Indian population and to elucidate their associated risk factors. Of 911 participants from the Sankara Nethralaya Diabetic Retinopathy and Molecular Genetics Study-II (SN-DREAMS-), 759 who underwent OCT were analysed. The participants underwent a comprehensive examination and retinal photography following a standard protocol for diabetic retinopathy (DR) grading. The subjects were categorized into centre-involving DME (CI-DME), non-centre involving DME (NCI-DME), and No-DME based on the mean retinal thickness at the central 1 mm, inner and outer ETDRS subfields. The prevalence of CI-DME and NCI-DME in the Chennai population was 3.03% (95% CI: 3.01-3.05) and 10.80% (95% CI: 10.7-11.02). NCI-DME was found to be higher by 9.5% (95% CI: 0.07-0.11) in the early stages of DR. A greater number of subjects with CI DME were aged >60 years and had diabetes mellitus (DM) for >10 years. The significant risk factors for NCI-DME are diastolic blood pressure, serum total cholesterol, serum triglyceride, insulin use and neuropathy (OR (95% CI): 0.97 (0.94-100), 1.00 (1.00-1.01), 0.99 (0.98-0.99), 2.32 (1.15-4.68) and 4.24 (1.22-14.69), respectively) and for CI DME are duration of diabetes, anaemia, neuropathy and insulin use (OR (95% CI): 2.49 (0.96-6.40), 3.41 (1.34-8.65), 10.58 (1.68-66.56) and 3.51 (1.12-10.95), respectively). The prevalence of NCI-DME was found to be higher than that of CI-DME in patients with DR.
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http://dx.doi.org/10.1080/09286586.2021.1907846DOI Listing
April 2021

G-Quadruplex Structures in Bacteria: Biological Relevance and Potential as an Antimicrobial Target.

J Bacteriol 2021 Jun 8;203(13):e0057720. Epub 2021 Jun 8.

Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, Indore, India.

DNA strands consisting of multiple runs of guanines can adopt a noncanonical, four-stranded DNA secondary structure known as G-quadruplex or G4 DNA. G4 DNA is thought to play an important role in transcriptional and translational regulation of genes, DNA replication, genome stability, and oncogene expression in eukaryotic genomes. In other organisms, including several bacterial pathogens and some plant species, the biological roles of G4 DNA and G4 RNA are starting to be explored. Recent investigations showed that G4 DNA and G4 RNA are generally conserved across plant species. analyses of several bacterial genomes identified putative guanine-rich, G4 DNA-forming sequences in promoter regions. The sequences were particularly abundant in certain gene classes, suggesting that these highly diverse structures can be employed to regulate the expression of genes involved in secondary metabolite synthesis and signal transduction. Furthermore, in the pathogen Mycobacterium tuberculosis, the distribution of G4 motifs and their potential role in the regulation of gene transcription advocate for the use of G4 ligands to develop novel antitubercular therapies. In this review, we discuss the various roles of G4 structures in bacterial DNA and the application of G4 DNA as inhibitors or therapeutic agents to address bacterial pathogens.
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http://dx.doi.org/10.1128/JB.00577-20DOI Listing
June 2021

Relationship between triglyceride glucose index, retinopathy and nephropathy in Type 2 diabetes.

Endocrinol Diabetes Metab 2021 01 19;4(1):e00151. Epub 2020 Aug 19.

Shri Bhagwan Mahavir Vitreoretinal Services Medical Research Foundation Chennai India.

Aims: To explore the relationship between TyG index, diabetic retinopathy (DR) and nephropathy.

Methods: This was a cross-sectional observational study that examined 1413 subjects with type 2 diabetes (both known and newly diagnosed). Subjects underwent a detailed standard evaluation to detect diabetic retinopathy (fundus photography) and nephropathy (defined as urinary albumin excretion ≥ 30 mg/24 h). The TyG index was calculated as ln (fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2) and stratified into 4 quartiles (TyG-Q). The baseline characteristics of the study population in the four TyG-Q (Q1 (≤7.3) n = 349, Q2 (>7.3 to ≤ 7.5) n = 358, Q3 (>7.5 to ≤ 8.0) n = 354, and Q4 (>8.0) n = 352) were analysed. Variables associated with the presence of DR and nephropathy were assessed using a stepwise binary logistic regression analysis.

Results: The presence of DR was associated with higher TyG index (OR = 1.453, =.001) and longer duration of diabetes (OR = 1.085,  < .001). The presence of nephropathy was associated with a higher TyG index (OR = 1.703,  < .001), greater age (OR = 1.031, < .001), use of insulin (OR = 1.842, = .033), higher systolic BP (OR = 1.015, < .001), and the presence of DR (OR = 3.052, < .001). Higher TyG-Q correlated with the severity of DR ( = .024), presence of nephropathy ( = .001), age ( < .001) and diastolic blood pressure ( = .006).

Conclusions: A higher TyG index is associated with the presence of retinopathy and nephropathy in individuals with diabetes and could be used for monitoring metabolic status in clinical settings.
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http://dx.doi.org/10.1002/edm2.151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831221PMC
January 2021

Central Serous Chorioretinopathy Analyzed by Multimodal Imaging.

Transl Vis Sci Technol 2021 Jan 8;10(1):15. Epub 2021 Jan 8.

Department of Ophthalmology, Columbia University, New York, New York, USA.

Purpose: We correlated quantitative fundus autofluorescence (qAF) with other fundus features in patients exhibiting central serous chorioretinopathy (CSC).

Methods: Short wavelength fundus autofluorescence (SW-AF, 488 nm excitation) was measured by qAF. Using nonnormalized images qAF values were calculated within eight concentric segments (qAF) located at an eccentricity of 7° to 9°. Horizontal spectral domain optical coherence tomography (SD-OCT) scans and near-infrared fundus autofluorescence images (NIR-AF) were studied.

Results: Thirty-six eyes of 20 patients (mean age 48.7± 8.5 years) diagnosed with CSC were studied. Thirteen patients had bilateral disease; four patients were female. In 22 eyes CSC was present in the macula; in one eye the lesion was in a peripapillary location, 10 involved both locations, and three were unaffected. Serous retinal detachment, retinal pigmented epithelial detachment (PED), outer retinal atrophy and subRPE hypertransmission were all features identifiable by SD-OCT. NIR-AF images were helpful in detecting foveal and parafoveal lesions. Sampling for retina-wide elevations in SW-AF intensity by measuring qAF did not indicate a generalizable relationship amongst CSC-diagnosed eyes. However, color-coded qAF images revealed alterations in SW-AF topography and intensity relative to healthy eyes at the same locations. Thus zones of higher than normal qAF intensity were found in association with SD-OCT detectable PED; loss of ellipsoid zone and interdigitation zone; and hyperreflectivity in outer retina. Pronounced decreases in qAF colocalized with serous retinal detachment and with outer retinal degeneration that included hypertransmission of SD-OCT signal into the choroid.

Conclusions: Localized elevations in qAF reflect increased bisretinoid in association with CSC lesions.

Translational Relevance: Foci of elevated qAF at some stages of CSC contribute to the natural history of the disease.
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http://dx.doi.org/10.1167/tvst.10.1.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804571PMC
January 2021

Visual Detection of SARS-CoV-2 RNA by Conventional PCR-Induced Generation of DNAzyme Sensor.

Front Mol Biosci 2020 23;7:586254. Epub 2020 Dec 23.

National Capital Region - Biotech Science Cluster, Translational Health Science and Technology Institute (THSTI), Faridabad, India.

The gold standard for the diagnosis of SARS-CoV-2, the causative agent of COVID-19, is real-time polymerase chain reaction (PCR), which is labor-intensive, expensive, and not widely available in resource-poor settings. Therefore, it is imperative to develop novel, accurate, affordable, and easily accessible assays/sensors to diagnose and isolate COVID-19 cases. To address this unmet need, we utilized the catalytic potential of peroxidase-like DNAzyme and developed a simple visual detection assay for SARS-CoV-2 RNA using a conventional thermal cycler by the PCR-induced generation of DNAzyme sensor. The performance of RT-PCR DNAzyme-based sensor was comparable to that of real-time PCR. The pilot scale validation of RT-PCR DNAzyme-based sensor has shown ~100% sensitivity and specificity in clinical specimens (nasopharyngeal swab, = 34), with a good correlation (Spearman = 0.799) with the Ct-value of fluorescence probe-based real-time PCR. These findings clearly indicate the potential of this inexpensive, sensitive, and specific molecular diagnostic test to extend our testing capabilities for the detection of SARS-CoV-2 to curtail COVID-19 transmission.
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http://dx.doi.org/10.3389/fmolb.2020.586254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793695PMC
December 2020

Possible therapeutic interventions in COVID-19 induced ARDS by cotinine as an ACE-2 promoter and AT-1R blocker.

Infect Disord Drug Targets 2020 Dec 18. Epub 2020 Dec 18.

Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab. India.

In these challenging times of the pandemic, as coronavirus disease 2019 (COVID-19) has taken over the planet, its complications such as acute respiratory distress syndrome (ARDS) have the potential to wipe out a large portion of our population. Whereas a serious lack of ventilators, vaccine being months away makes the condition even worse. That's why promising drug therapy is required. One of them was suggested in this article. It is the angiotensin-converting enzyme-2 (ACE-2) to which the COVID-19 virus binds and upon downregulation of which the pulmonary permeability increases and results in the filling of alveoli by proteinaceous fluids, which finally results in ARDS. ARDS can be assisted by angiotensinII type-1 receptor (AT-1R) blocker and ACE-2 upregulator. AT-1R blocker will prevent vasoconstriction, the proinflammatory effect seen otherwise upon its activation. ACE-2 upregulation will ensure less formation of angiotensin II, vasodilatory effects due to the formation of angiotensin (1-7), increased breakdown of bradykinin at lung level. Overall, decreased vasoconstriction of vessels supplying lungs and decreased vasodilation of lung tissues will ensure decreased pulmonary permeability and eventually relieve ARDS. It should also be considered that all components of the reninangiotensin-aldosterone system (RAAS) are located in the lung tissues. A drug with the least plasma protein binding is required to ensure its distribution across these lung tissues. Cotinine appears to be a promising candidate for COVID-19- induced ARDS. It acts across the board and acts as both an AT-1R blocker, ACE-2 upregulator. It also has a weak plasma protein binding that helps to spread through the lung tissues. In this review, we summarized that cotinine, along with COVID-19 virus replication blocker anti-virals, may prove to be a promising therapy for the treatment of COVID-19 induced ARDS.
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http://dx.doi.org/10.2174/1871526520666201218153554DOI Listing
December 2020

Chromatic response of a four-telescope integrated-optics discrete beam combiner at the astronomical L band.

Opt Express 2020 Nov;28(23):34346-34361

We show the results of simulation and experimental study of a 4-telescope zig-zag discrete beam combiner (DBC) for long-baseline stellar interferometry working at the astronomical L band (3 - 4 µm) under the influence of a narrow bandwidth light source. Following Saviauk et al. (2013), we used a quasi-monochromatic visibility-to-pixel matrix (V2PM) for retrieving the complex coherence functions from simulated and experimentally measured power at the output of the device. Simulation and coefficient of determination (R) measurements show that we are able to retrieve the visibility amplitudes with >95 % accuracy of our chromatic model source up to a bandwidth of 100 nm centred at 3.5 µm. We characterized a DBC manufactured by 3D ultra-fast laser inscription (ULI) written on gallium lanthanum sulphate (GLS). Experimental results showed retrieval of visibility amplitude with an accuracy of 80-90 % at 69 nm bandwidth, validating our simulation. The standard deviation of experimental phase residuals are between 0.1-0.4 rad, which shows that the retrieval procedure is sufficient to get good quality images, where phase perturbations of less than 1 rad are expected under good seeing conditions for astronomical applications.
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http://dx.doi.org/10.1364/OE.405896DOI Listing
November 2020

Hydroxychloroquine and QT prolongation: reassuring data in approved indications.

Rheumatol Adv Pract 2020 21;4(2):rkaa044. Epub 2020 Aug 21.

Medical Affairs, Ipca Laboratories Limited, Mumbai, India.

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http://dx.doi.org/10.1093/rap/rkaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607156PMC
August 2020

Genome-wide analysis of PHD finger gene family and identification of potential miRNA and their PHD finger gene specific targets in indica.

Noncoding RNA Res 2020 Dec 27;5(4):191-200. Epub 2020 Oct 27.

University School of Biotechnology, Guru Gobind Singh Indraprastha University, Sec-16C, Dwarka, New Delhi, India.

Rice ( L.) is one of the most important cereal crops for one third of the world population. However, the grain quality as well as yield of rice is severely affected by various abiotic stresses. Environmental stresses affect the expression of various microRNAs (miRNAs) which in turn negatively regulate gene expression at the post-transcriptional level either by degrading the target mRNA genes or suppressing translation in plants. Plant homeo-domain (PHD) finger proteins are known to be involved in the plant response to salinity stress. In the present study, we identified 44 putative finger genes in Indica, using Ensembl Plants Database. Using computational approach, potential miRNAs that target finger genes were identified. Out of the 44 finger genes only three finger genes i.e., and , were found to be targeted by five newly identified putative miRNAs i.e., ath-miRf10010-akr, ath-miRf10110-akr, osa-miR1857-3p, osa-miRf10863-akr, and osa-miRf11806-akr. This is the first report of these five identified miRNAs on targeting PHD finger in Indica. Further, expression analysis of 44 PHD finger genes under salinity was also performed using quantitative Real-Time PCR. The expression profile of 8 genes were found to be differentially regulated, among them two genes were significantly up regulated i.e., and . protein-protein interaction analysis using STRING database showed interaction of the OsPHD finger proteins with other protein partners that are directly or indirectly involved in development and abiotic stress tolerance.
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http://dx.doi.org/10.1016/j.ncrna.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610035PMC
December 2020

Development of Hillchol®, a low-cost inactivated single strain Hikojima oral cholera vaccine.

Vaccine 2020 11 31;38(50):7998-8009. Epub 2020 Oct 31.

Department of Microbiology and Immunology at Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. Electronic address:

Cholera remains an important global health problem with up to 4 million cases and 140,000 deaths annually. Oral cholera vaccines (OCVs) are now a cornerstone of the WHOs "Ending Cholera - A Global Roadmap to 2030" global program for the eventual elimination of cholera. There are currently three WHO prequalified OCVs available, Dukoral®, Shanchol® and Euvichol-Plus®. These vaccines are effective but due to a multiple strain composition and two different methods of inactivation, are complex and costly to manufacture. We describe here the characterization and industrial scale development of Hillchol®; a novel, likely affordable single-component OCV for low and middle-income countries. Hillchol® consists of formalin-inactivated bacteria of a stable recombinant Vibrio cholerae O1 El Tor Hikojima serotype strain expressing approximately 50% each of Ogawa and Inaba O1 LPS antigens. The novel OCV can be manufactured on an industrial scale at a low cost. Hillchol® was well tolerated in animal toxicology studies and shown to have non-inferior oral immunogenicity in mice for both intestinal-mucosal and serological immune responses when compared with a WHO-prequalified OCV. The optimized production of this single component OCV will reduce cost of OCV production and thus substantially increase vaccine availability. Based on these results, Hillchol® has been produced at a GMP facility and used successfully for clinical phase I/II studies.
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http://dx.doi.org/10.1016/j.vaccine.2020.10.043DOI Listing
November 2020

Filtering noise in time and frequency domain for ultrafast pump-probe performed using low repetition rate lasers.

Rev Sci Instrum 2020 Oct;91(10):103901

Nano Science Laboratory, Materials Science Section, Raja Ramanna Centre for Advanced Technology, Indore 452013, India.

Optical pump-probe spectroscopy is a powerful tool to directly probe the carrier dynamics in materials down to sub-femtosecond resolution. To perform such measurements, while keeping the pump induced perturbation to the sample as small as possible, it is essential to have a detection scheme with a high signal to noise ratio. Achieving such a high signal to noise ratio is easy with phase sensitive detection based on a lock-in-amplifier when a high repetition rate laser is used as the optical pulse source. However, such a lock-in-amplifier based method does not work well when a low repetition rate laser is used for the measurement. In this article, a sensitive detection scheme, which combines the advantages of a boxcar that rejects noise in time domain and a lock-in-amplifier that isolates the signal in the frequency domain for performing pump-probe measurements using a low-repetition rate laser system, is proposed and experimentally demonstrated. A theoretical model to explain the process of signal detection and a method to reduce the pulse to pulse energy fluctuation in probe pulses is presented. By performing pump-probe measurements at various detection conditions, the optimum condition required for obtaining the transient absorption signal with low noise is presented. The reported technique is not limited to pump-probe measurements and can be easily modified to suit for other sensitive measurements at low repetition rates.
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http://dx.doi.org/10.1063/5.0010449DOI Listing
October 2020

Exploring Computational and Biophysical Tools to Study the Presence of G-Quadruplex Structures: A Promising Therapeutic Solution for Drug-Resistant .

Front Genet 2020 25;11:935. Epub 2020 Sep 25.

Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India.

, a gram-negative bacterium that causes cholera, has already caused seven major pandemics across the world and infects roughly 1.3-4 million people every year. Cholera treatment primarily involves oral rehydration therapy supplemented with antibiotics. But recently, multidrug-resistant strains of have emerged. High genomic plasticity further enhances the pathogenesis of this human pathogen. Guanines in DNA or RNA assemble to form G-quadruplex (GQ) structures which have begun to be seen as potential drug targeting sites for different pathogenic bacteria and viruses. In this perspective, we carried out a genome-wide hunt in using a bio-informatics approach and observed ∼85 G-quadruplex forming motifs (VC-PGQs) in chromosome I and ∼45 putative G-quadruplexs (PGQs) in chromosome II. Ten putative G-quadruplex forming motifs (VC-PGQs) were selected on the basis of conservation throughout the genus and functional analysis displayed their location in the essential genes encoding bacterial proteins, for example, methyl-accepting chemotaxis protein, orotate phosphoribosyl transferase protein, amidase proteins, etc. The predicted VC-PGQs were validated using different bio-physical techniques, including Nuclear Magnetic Resonance spectroscopy, Circular Dichroism spectroscopy, and electrophoretic mobility shift assay, which demonstrated the formation of highly stable GQ structures in the bacteria. The interaction of these VC-PGQs with the known specific GQ ligand, TMPyP4, was analyzed using ITC and molecular dynamics studies that displayed the stabilization of the VC-PGQs by the GQ ligands and thus represents a potential therapeutic strategy against this enteric pathogen by inhibiting the PGQ harboring gene expression, thereby inhibiting the bacterial growth and virulence. In summary, this study reveals the presence of conserved GQ forming motifs in the genome that has the potential to be used to treat the multi-drug resistance problem of the notorious enteric pathogen.
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http://dx.doi.org/10.3389/fgene.2020.00935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545536PMC
September 2020

Association of Hydroxychloroquine Use With Decreased Incident Atrial Fibrillation in Systemic Lupus Erythematosus.

Arthritis Care Res (Hoboken) 2021 Jun;73(6):828-832

Allegheny Health Network, Pittsburgh, Pennsylvania.

Objective: To study the relationship between hydroxychloroquine (HCQ) use and new-onset atrial fibrillation in patients with systemic lupus erythematosus (SLE).

Methods: A retrospective cohort of adult patients with SLE was constructed from December 1, 2014 to May 30, 2017. Patients were categorized as either HCQ users or nonusers. The primary outcome was incident atrial fibrillation. Secondary outcomes included incident ventricular arrhythmias (composite of ventricular tachycardia, ventricular fibrillation, or torsades de pointes). Outcomes were adjudicated by review of the electronic health record. Statistical analyses included simple and multivariable logistic regression tests to estimate the association between HCQ use and incident atrial fibrillation after adjusting for relevant confounders. Propensity score matching analysis was completed.

Results: Our study included 1,647 patients with SLE, of which 917 were HCQ users and 730 were nonusers. A total of 23 atrial fibrillation events occurred, including 3 in HCQ users and 20 in nonusers. Logistic regression analysis showed an odds ratio (OR) of 0.12 (95% confidence interval [95% CI] 0.034-0.39, P = 0.0005) for incident atrial fibrillation and 2.39 (95% CI 0.25-23.0, P = 0.45) for ventricular arrhythmias. Results remained significant in the fully adjusted and propensity score-matched models.

Conclusion: In this exploratory study, HCQ use was associated with an 88% decrease in the risk of incident atrial fibrillation in patients with SLE. Considering the increased cardiovascular risk in SLE, incorporation of HCQ into the regimen may be beneficial for both disease manifestations and reducing the risk of atrial fibrillation. Further studies would be needed to confirm the antifibrillatory benefit of this relatively safe and low-cost medication.
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http://dx.doi.org/10.1002/acr.24494DOI Listing
June 2021

GOLD SELEX: a novel SELEX approach for the development of high-affinity aptamers against small molecules without residual activity.

Mikrochim Acta 2020 Oct 19;187(11):618. Epub 2020 Oct 19.

Aptamer Technology and Diagnostics Laboratory, Multidisciplinary Clinical and Translational Research Group, Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, 121001, India.

GOLD SELEX, a novel SELEX approach has been developed that obviates the need for target immobilization for aptamer development. The approach purely relies on the affinity of the aptamers towards its target, to get detached from the gold nanoparticle (GNP) surface (weak attraction) after binding with its target. Thus, only the completely detached aptamers are selected for the next round of SELEX. This, in-process, also addresses the issue of residual binding and thus improves the sensitivity of the developed aptamers. As a proof of concept for establishing the utility of the approach for small molecules, we have developed aptamers against dichlorvos (DV), a pesticide in just 8 rounds. Using these aptamer candidates, we have developed an aptamer-NanoZyme (GNP having peroxidase mimic activity) based colorimetric assay. The developed aptamer displayed high affinity (K in sub micromolar range) and selectivity for DV. The developed assay could detect as low as 15 μM DV. The best-performing aptamer was also able to work in real samples like river water and commercial apple juice. The GOLD SELEX approach developed in this study, we believe, can act as a template for future SELEX strategy development and can replace the conventional SELEX strategy.
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http://dx.doi.org/10.1007/s00604-020-04577-0DOI Listing
October 2020

An Aptamer Linked Immobilized Sorbent Assay (ALISA) to Detect Circulatory IFN-α, an Inflammatory Protein among Tuberculosis Patients.

ACS Comb Sci 2020 11 16;22(11):656-666. Epub 2020 Oct 16.

Aptamer Technology and Diagnostics Laboratory, Multidisciplinary Clinical and Translational Research Group, Translational Health Science and Technology Institute, Incubator, NCR Biotech Science Cluster, Third Milestone, Faridabad, Gurgaon Expressway, Faridabad, 121001, India.

Dysregulation of IFN-α is the basis for pathogenesis of autoimmune as well as infectious diseases. Identifying inflammatory signatures in peripheral blood of patients is an approach for monitoring active infection. Hence, estimation of type I IFNs as an inflammatory biomarker to scrutinize disease status after treatment is useful. Accordingly, an Aptamer Linked Immobilized Sorbent Assay (ALISA) for the detection of IFN-α in serum samples was developed. Sixteen aptamers were screened for their ability to bind IFN-α. Aptamer IFNα-3 exhibited specificity for IFN-α with no cross-reactivity with interferons β and γ and human serum albumin. The disassociation constant () was determined to be 3.96 ± 0.36 nM, and the limit of detection was ∼2 ng. The characterized IFNα-3 aptamer was used in ALISA to screen tuberculosis (TB) patients' sera. An elevated IFN-α level in sera derived from untreated TB patients (median = 0.31), compared to nontuberculous household contacts (median = 0.13) and healthy volunteers (median = 0.12), and further a decline in IFN-α level among treated patients (median = 0.13) were seen. The ALISA assay facilitates direct estimation of inflammatory protein(s) in circulation unlike mRNA estimation by real time PCR. Designing of aptamers similar to the IFNα-3 aptamer provides a novel approach to assess other inflammatory protein(s) in patients before, during, and after completion of treatment and would denote clinical improvement in successfully treated patients.
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http://dx.doi.org/10.1021/acscombsci.0c00108DOI Listing
November 2020

AuNPs/CNF-modified DNA biosensor for early and quick detection of in patients suffering from scrub typhus.

3 Biotech 2020 Oct 19;10(10):446. Epub 2020 Sep 19.

Amity Center of Nanotechnology, Amity University, Haryana, 122413 India.

A novel approach has been developed for the detection of  - (TSA) gene of  a causative agent of scrub typhus disease. The approach was developed by immobilization of 5' NH2 labeled ssDNA probe selective    gene, to the surface of AuNPs/CNF modified screen-printed electrode. An electrochemical response was recorded with single stranded genomic DNA (ssDNA) of isolated from patient sample, using cyclic voltammetry and electrochemical impedance spectroscopy. The electrode surface was characterized by Field-Emission Scanning electron microscope (FE-SEM), Fourier Transform Infrared Spectroscopy (FTIR) and Raman Spectroscopy at each step of fabrication. The DNA biosensor shows optimum response within 50-60 s at room temperature (25 ± 3 °C). The sensor shows higher sensitivity [7849 (µA/cm)/ng DNA], fast response time (60 s), wider linear range (0.04-2.6 ng) with limit of detection of 0.02 ng/µl of ssDNA sample.
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http://dx.doi.org/10.1007/s13205-020-02432-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502116PMC
October 2020

G-quadruplex stabilization in the ions and maltose transporters gene inhibit Salmonella enterica growth and virulence.

Genomics 2020 11 6;112(6):4863-4874. Epub 2020 Sep 6.

Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Simrol, Indore 453552, India. Electronic address:

The G-quadruplex structure is a highly conserved drug target for preventing infection of several human pathogens. We tried to explore G-quadruplex forming motifs as promising drug targets in the genome of Salmonella enterica that causes enteric fever in humans. Herein, we report three highly conserved G-quadruplex motifs (SE-PGQ-1, 2, and 3) in the genome of Salmonella enterica. Bioinformatics analysis inferred the presence of SE-PGQ-1 in the regulatory region of mgtA, SE-PGQ-2 in ORF of entA, and SE-PGQ-3 in the promoter region of malE and malK genes. The G-quadruplex forming sequences were confirmed by biophysical and biomolecular techniques. Cellular studies affirm the inhibitory effect of G-quadruplex specific ligands on Salmonella enterica growth. Further, PCR inhibition, reporter based assay, and RT-qPCR assays emphasize the biological relevance of G-quadruplexes in these genes. Thus, this study confirmed the presence of G-quadruplex motifs in Salmonella enterica and characterized them as a promising drug target.
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http://dx.doi.org/10.1016/j.ygeno.2020.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474834PMC
November 2020

Effects of Ramadan fasting on serum lipid profile.

J Family Med Prim Care 2020 May 31;9(5):2337-2341. Epub 2020 May 31.

Assistant Professor Pharmacology, SLBSMC NerChowk, Mandi, India.

Introduction: Ramadan is the ninth month in the lunar Islamic calendar and lasts for about 29-30 days. It is mandatory for all adult individuals of the Islamic faith to fast during the holy month of Ramadan. During this period, healthy Muslims do not eat or drink (i.e., total abstinence from food and fluids) and refrain from tobacco, daily from pre-dawn until dusk (21). Very few studies in the recent years have been conducted on this subject and for primary care physicians, it is of great help in understanding the physiological changes that occur in various populations with different rituals in Muslims.

Materials And Methods: The present study included healthy adult male Muslim volunteers from different mosques in and around Jammu city. The number of subjects in the study was 100. Blood samples from all 100 subjects were collected twice during the study-once in the week prior to the beginning of Ramadan and then again in the last week of Ramadan (from 98 subjects as 2 subjects opted out). Following biochemical parameters were taken into consideration: (a) Serum total cholesterol (b) Serum triglycerides (c) Serum HDL cholesterol.

Results: It was observed that compared to pre-fasting levels, total cholesterol (TC) and triglycerides (TG) were significantly decreased (P = 0.000) and high-density lipoprotein cholesterol (HDL-C) level had significantly increased (P = 0.000).

Conclusion: This study showed a reduction in total cholesterol and triglycerides along with a rise in levels of HDL-C, which had beneficial effects on lipid profile post Ramadan fasting period.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_550_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380785PMC
May 2020

Conserved G-Quadruplex Motifs in Gene Promoter Region Reveals a Novel Therapeutic Approach to Target Multi-Drug Resistance .

Front Microbiol 2020 26;11:1269. Epub 2020 Jun 26.

Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India.

An opportunistic pathogen, is known to cause life-threating nosocomial infection with a high rate of morbidity and mortality. Evolutions of multi-drug-resistant and hyper-virulent strains of make the situation worse. Currently, there is no incisive drug molecule available for drug-resistant hyper-virulent infection that emphasizes the need for identification of novel and more promising drug targets in . Recently, various non-canonical structures of nucleic acids especially G-quadruplex (G4) motifs have been identified as potential therapeutic targets against several human pathogenic bacteria and viruses including , , human immunodeficiency virus (HIV), Ebola, and Nipah. Therefore, in present study we screened the genomes for identification of evolutionary conserved G4 structure-forming motifs as promising anti-bacterial drug targets. Bioinformatics analysis revealed the presence of six highly conserved G4 motifs in the promoter region of five essential genes that play a critical role in nutrient transport and metabolism. Biophysical studies showed the formation of G4 structure by these conserved motifs. Circular Dichroism melting analysis showed the stabilization of these G4 motifs by a well-known G4-stabilizing agent, BRACO-19. The stabilization of these motifs by BRACO-19 was also able to stop the primer extension process, which is an essential phenomenon for expression of the G4-harboring gene. The addition of G4-specific ligand at low micromolar range was observed to be lethal for the growth of this bacteria and negatively controlled the expression of the G4-harboring genes via G4 structure stabilization. These observations strengthen the formation of G4 structures by the predicted G4 motif , which can be stabilized by G4 ligands like BRACO-19. This stabilization of G4 structures can attenuate the expression of G4-harboring essential genes and thus play a critical role in the regulation of gene expression. Thus, taking all given result in consideration, for the first time, this study showed the new therapeutic avenue for combating infection by characterizing the conserved G4 motifs as promising therapeutic targets.
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http://dx.doi.org/10.3389/fmicb.2020.01269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344255PMC
June 2020

2020 American College of Rheumatology Guideline for the Management of Gout.

Arthritis Care Res (Hoboken) 2020 06 11;72(6):744-760. Epub 2020 May 11.

American College of Rheumatology, Atlanta, Georgia.

Objective: To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations.

Methods: Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional.

Results: Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.

Conclusion: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.
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http://dx.doi.org/10.1002/acr.24180DOI Listing
June 2020

2020 American College of Rheumatology Guideline for the Management of Gout.

Arthritis Rheumatol 2020 06 11;72(6):879-895. Epub 2020 May 11.

American College of Rheumatology, Atlanta, Georgia.

Objective: To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations.

Methods: Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional.

Results: Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.

Conclusion: Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.
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http://dx.doi.org/10.1002/art.41247DOI Listing
June 2020

Clinical profile of patients with hyponatremia in a tertiary care hospital in the sub-Himalayan region.

J Family Med Prim Care 2020 Feb 28;9(2):834-838. Epub 2020 Feb 28.

Professor and Head, Department of Medicine, Dr. Rajendra Prasad Government Medical College, Tanda, Kangra, Himachal Pradesh (DRPGMCH), India.

Introduction: Hyponatremia, defined as a serum sodium concentration ([Na+]) <135 mEq/L. It is not a disease but rather a pathophysiologic process indicating disturbed water homeostasis. Hyponatremia should be further classified to provide directions for diagnosis and treatment. It is a heterogeneous disorder. The classifications of hyponatremia are commonly based on tonicity and volume status. The initial differentiation in hypotonic and non-hypotonic hyponatremia is important because management is different. Several studies have been conducted previously to measure the incidence of hyponatremia in medically ill patients. Several studies have demonstrated an increased prevalence of hyponatremia in the presence of co-morbid conditions. We conducted this study to bring out various causes of hyponatremia; their relation with sex, age and outcome and hyponatremia's classification and incidence in our hospitalised population.

Materials And Methods: This study was conducted to find out etiology, classification, prevalence and outcome and its relation with age and sex in patients of hyponatremia admitted in our institution. A total number of 106 patients were studied.

Results: Hospital-based incidence of hyponatremia was found to be 1.17%. Mean age of patients in study was 62.25 ± 17.7 years. Male to female ratio was 1.25:1. Altered sensorium was the most common neurological symptom. Ninety-five (90%) patients were hypo-osmolar. Out of ninety four patients, 38 (40%) were euvolemic. Chronic obstructive pulmonary disorder (COPD) with cor pulmonale with right-sided heart failure ( = 9, 31%) was the most common cause in hyper-volemic hyponatremia. Acute gastroenteritis ( = 13, 48%) was the most common cause in hypo-volemic hyponatremia. Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) was the most common cause ( = 20, 53%) of euvolemic hyponatremia. Out of 106 patients, 11 (10.38%) patients expired.

Conclusion: Hyponatremia acts as a poor prognostic marker of the primary disease. It is important to recognise it early because of the potential morbidity and mortality, economic impact on the patients and health care associated with it. Early management of hyponatremia, which includes determination of the rate of correction, the appropriate interventions and the presence of other underlying disorders, may help in improving the outcome and shortening the hospital stay of the patients.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_788_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113994PMC
February 2020

Letter to the editor regarding: Refaat B., et al., The performances of serum activins and follistatin in the diagnosis of ectopic pregnancy: A prospective case-control study, Clin Chim Acta 500 (2020) 69-74.

Clin Chim Acta 2020 07 19;506:135. Epub 2020 Mar 19.

Department of Biochemistry, SMS Medical College & Attached Hospitals, Jaipur 302004, Rajasthan, India.

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http://dx.doi.org/10.1016/j.cca.2020.03.027DOI Listing
July 2020

A Validated LC-MS/MS Method for Simultaneous Determination of 3-O-Acetyl-11-Keto-β-Boswellic Acid (AKBA) and its Active Metabolite Acetyl-11-Hydroxy-β-Boswellic Acid (Ac-11-OH-BA) in Rat Plasma: Application to a Pharmacokinetic Study.

J Chromatogr Sci 2020 Jun;58(6):485-493

Trivedi Science Research Laboratory, Thane-West, Maharashtra, India.

The aim of this study was to develop and validate a new, rapid, sensitive, selective and reliable liquid chromatography-tandem mass spectrometry method for simultaneous determination of 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) and its active metabolite 3-O-Acetyl-11-hydroxy-β-boswellic acid (Ac-11-hydroxy-BA) in rat plasma. Both analytes (AKBA and Ac-11-hydroxy-BA) and the internal standard (IS, ursolic acid) were extracted from 100 μL of rat plasma by protein precipitation. Chromatographic separation was achieved on PRP-H1 RP-C18 column (75 mm × 2 mm, 1.6 μm) using acetonitrile-water (95.5 v/v) as the mobile phase. Mass detection was conducted by electrospray ionization in positive ion multiple reaction monitoring (MRM) mode. A linear dynamic range of 1-1,000 ng/mL for both AKBA and Ac-11-hydroxy-BA was established with mean correlation coefficient (r (1)) of 0.999. Intra- and inter-day precision (% CV) of analysis were found in the range of 1.9-7.4%. The accuracy determined for these analytes ranged from 92.4 to 107.2%. The extraction recoveries for both analytes ranged from 92.6 to 97.3% for spiked plasma samples and were consistent. The % change in stability samples compared to nominal concentration ranged from 0.4 to 4.2%. This method was successfully tested to a pharmacokinetic (PK) study for estimation of AKBA and acetyl-11-hydroxy-BA in rat plasma following oral administration of AKBA. This method has been validated with the advantage of shorter run time that can be used for high-throughput analysis and has been successfully applied to the pharmacokinetic study of AKBA in rats.
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http://dx.doi.org/10.1093/chromsci/bmaa010DOI Listing
June 2020

Intra-Arterial Chemotherapy for Retinoblastoma: Four-Year Results from Tertiary Center in India.

Ocul Oncol Pathol 2020 Jan 4;6(1):66-73. Epub 2019 Jun 4.

Apollo Institute of Interventional Radiology, Apollo Hospital, Chennai, India.

Background: There are limited reports of intra-arterial chemotherapy (IAC) for retinoblastoma (RB) from developing world.

Objectives: In this study, we report our 4-year experience of IAC for RB from India.

Methods: Retrospective, interventional case series. Primary outcome measures included tumor regression, vitreous seeds and subretinal seeds control, and globe salvage. Secondary outcome measures were best-corrected visual acuity and treatment complications.

Results: Fifteen eyes underwent 53 IAC procedures over mean 28.6 ± 13.8 months (range 10-51 months). IAC was employed as primary ( = 6) or secondary ( = 9) chemotherapy. Following IAC, complete regression of main tumor was seen in 7 eyes (47%) and partial regression in 3 (20%) eyes. Enucleation was done in 5(33%) eyes. Globe salvage rates were achieved in 1 eye (100%) in group B, 2 eyes (67%) in group C ( = 3), 6 eyes (67%) in group D ( = 9), and 1 eye (50%) in group E ( = 2). Following IAC, Kaplan-Meier survival curve showed 93% globe survival rate at 1 year, 76% at 2 years, and 66% at 3, and 4 years.

Conclusion: IAC has enhanced globe salvage rates in eyes with RB. Multicenter studies with longer follow-up are necessary to better understand outcomes in the long term.
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http://dx.doi.org/10.1159/000500010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984160PMC
January 2020

Outcomes of surgery in eyes with familial exudative vitreoretinopathyassociated retinal detachment.

Can J Ophthalmol 2020 06 13;55(3):253-262. Epub 2020 Jan 13.

Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai, India.

Objective: The aim of this study was to evaluate various techniques of surgical treatment of retinal detachment associated with familial exudative vitreoretinopathy (FEVR) and the factors affecting the anatomical and visual outcome.

Design: Retrospective case series.

Participants: Patients diagnosed with FEVR associated retinal detachment and operated for the same between January 2004 and September 2017.

Methods: A retrospective chart review was conducted of all patients diagnosed with FEVR between January 2004 and September 2017. Patients with rhegmatogenous retinal detachment (RRD) and tractional retinal detachment (TRD) were included for analysis. Statistical analysis was performed using the t test for mean visual acuities, Fisher's exact test for categorical data, and the one-way analysis of variance for visual outcomes among surgical management options.

Results: A total of 44 eyes of 38 patients diagnosed with FEVR-associated retinal detachment and operated for the same were evaluated. At the time of initial presentation, the mean age of the 38 patients was 14.6 ± 10.9 years and 57.8% were males. Out of 44 eyes that underwent surgical intervention, 79.5% cases were of RRD (n = 35), and TRD was seen in 20.5% cases (n = 9). Primary management in the form of scleral buckle was done in 14 (31.8%) eyes, with 11 eyes (78.6%) having an attached retina after a single surgery and 85.7% after multiple surgeries. Primary pars plana vitrectomy (PPV) was done in 30 (68.2%) eyes, of which 73.3% had attached retina after single surgery and 83.8% after multiple surgeries. Poor pre-operative best-corrected visual acuity, presence of TRD, and presence of falciform folds were associated with poor anatomical outcome.

Conclusions: Favourable outcomes can be achieved, though multiple surgical interventions may, however, be necessary for the ultimate success in some cases.
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http://dx.doi.org/10.1016/j.jcjo.2019.11.001DOI Listing
June 2020