Publications by authors named "Manish Bansal"

177 Publications

Management of Dyslipidaemia for the Prevention of Stroke: Clinical Practice Recommendations from the Lipid Association of India.

Curr Vasc Pharmacol 2021 Nov 9. Epub 2021 Nov 9.

Medicine and Preventive Cardiology, Arihant Hospital and Research Center, Indore, Madhya Pradesh. India.

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in a very high risk group and extreme risk group (category A) of <50 mg/dl (1.3 mmol/l) while the LDL-C goal for extreme risk group (category B) is ≤30 mg/dl (0.8 mmol/l). High intensity statins are the first-line lipid lowering therapy. Non-statin therapy like ezetimibe and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors may be added as an adjunct to statins in patients who do not achieve LDL-C goals statins alone. In acute ischaemic stroke, high intensity statin therapy improves neurological and functional outcomes regardless of thrombolytic therapy. Although conflicting data exist regarding increased risk of intracerebral haemorrhage (ICH) with statin use, the overall benefit risk ratio favors long-term statin therapy necessitating detailed discussion with the patient. Patients who have statins withdrawn while being on prior statin therapy at the time of acute ischaemic stroke have worse functional outcomes and increased mortality. LAI recommends that statins be continued in such patients. In patients presenting with ICH, statins should not be started in the acute phase but should be continued in patients who are already taking statins. ICH patients, once stable, need risk stratification for atherosclerotic cardiovascular disease (ASCVD).
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http://dx.doi.org/10.2174/1570161119666211109122231DOI Listing
November 2021

Changing pattern of admissions for acute myocardial infarction in India during the COVID-19 pandemic.

Indian Heart J 2021 Jul-Aug;73(4):413-423. Epub 2021 Jun 18.

Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India.

Aim: Studies on the changes in the presentation and management of acute myocardial infarction (AMI) during the COVID-19 pandemic from low- and middle-income countries are limited. We sought to determine the changes in the number of admissions, management practices, and outcomes of AMI during the pandemic period in India.

Methods & Results: In this two-timepoint cross-sectional study involving 187 hospitals across India, patients admitted with AMI between 15th March to 15th June in 2020 were compared with those admitted during the corresponding period of 2019. We included 41,832 consecutive adults with AMI. Admissions during the pandemic period (n = 16414) decreased by 35·4% as compared to the corresponding period in 2019 (n = 25418). We observed significant heterogeneity in this decline across India. The weekly average decrease in AMI admissions in 2020 correlated negatively with the number of COVID cases (r = -0·48; r = 0·2), but strongly correlated with the stringency of lockdown index (r = 0·95; r = 0·90). On a multi-level logistic regression, admissions were lower in 2020 with older age categories, tier 1 cities, and centers with high patient volume. Adjusted utilization rate of coronary angiography, and percutaneous coronary intervention decreased by 11·3%, and 5·9% respectively.

Conclusions: The magnitude of reduction in AMI admissions across India was not uniform. The nature, time course, and the patient demographics were different compared to reports from other countries, suggesting a significant impact due to the lockdown. These findings have important implications in managing AMI during the pandemic.
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http://dx.doi.org/10.1016/j.ihj.2021.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424286PMC
November 2021

Endovascular Repair of a Descending Thoracic Aortic Aneurysm in a Pediatric Patient with Tuberous Sclerosis: A Case Report and Review of the Literature.

Pediatr Cardiol 2021 Sep 1. Epub 2021 Sep 1.

Charles E. Mullins Cardiac Catheterization Laboratories, Texas Children's Hospital, and Lillie Frank and Abercrombie Section of Cardiology, Department of Pediatrics, Baylor College of Medicine, 6651 Main Street Suite E-1920, Houston, TX, 77025, USA.

Aortic aneurysm in children is rare, but has been described in the tuberous sclerosis complex (TSC) population. While surgical repair has been utilized as the primary means of intervention, we present the first known case reporting exclusion of a descending thoracic aortic aneurysm with percutaneous covered stent implantation in a pediatric patient with TSC. A review of the literature is also included herein.
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http://dx.doi.org/10.1007/s00246-021-02717-8DOI Listing
September 2021

Radiation-Induced Pan-Valvular Involvement: A Rare Case Report.

Heart Views 2021 Jan-Mar;22(1):54-58. Epub 2021 Apr 22.

Department of Cardiology, Medanta-The Medicity, Gurgaon, Haryana, India.

Radiotherapy is an important treatment modality for various thoracic malignancies but is associated with long-term risk of radiation-associated valve disease (RAVD). We hereby report a case of a lady who had received radiotherapy 30 years back for carcinoma breast and was now found to be having clinically significant RAVD involving all the four cardiac valves. Simultaneous involvement of all the four valves in RAVD is extremely rare and has not been reported previously.
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http://dx.doi.org/10.4103/HEARTVIEWS.HEARTVIEWS_66_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254163PMC
April 2021

Heterotopic caval valve implantation in severe tricuspid regurgitation.

Ann Card Anaesth 2021 Jul-Sep;24(3):365-368

Cardiac Anesthesia and Critical Care, Medanta-The Medicity, Gurugram, Haryana, India.

Severe symptomatic tricuspid regurgitation (TR) with right heart failure is associated with significant morbidity and mortality. Medical therapy is often ineffective and surgical correction is not feasible due to prohibitive perioperative risk. Transcatheter caval valve implantation (CAVI) is an evolving therapeutic option for this condition. It refers to the heterotopic placement of a valve into the inferior vena cava alone or with a second valve in the superior vena cava to restrict the backflow from the failing tricuspid valve. We hereby describe a patient with previous mitral valve surgery with chronic severe TR who underwent successful CAVI at our institute.
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http://dx.doi.org/10.4103/aca.ACA_72_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404582PMC
November 2021

Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses and Inhibit Viral Replication .

Front Immunol 2021 26;12:613045. Epub 2021 Mar 26.

Translational Health Science & Technology Institute, National Capital Region (NCR) Biotech Science Cluster, Faridabad, India.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiates infection by attachment of the surface-exposed spike glycoprotein to the host cell receptors. The spike glycoprotein (S) is a promising target for inducing immune responses and providing protection; thus the ongoing efforts for the SARS-CoV-2 vaccine and therapeutic developments are mostly spiraling around S glycoprotein. The matured functional spike glycoprotein is presented on the virion surface as trimers, which contain two subunits, such as S1 (virus attachment) and S2 (virus fusion). The S1 subunit harbors the N-terminal domain (NTD) and the receptor-binding domain (RBD). The RBD is responsible for binding to host-cellular receptor angiotensin-converting enzyme 2 (ACE2). The NTD and RBD of S1, and the S2 of S glycoprotein are the major structural moieties to design and develop spike-based vaccine candidates and therapeutics. Here, we have identified three novel epitopes (20-amino acid peptides) in the regions NTD, RBD, and S2 domains, respectively, by structural and immunoinformatic analysis. We have shown as a proof of principle in the murine model, the potential role of these novel epitopes in-inducing humoral and cellular immune responses. Further analysis has shown that RBD and S2 directed epitopes were able to efficiently inhibit the replication of SARS-CoV-2 wild-type virus suggesting their role as virus entry inhibitors. Structural analysis revealed that S2-epitope is a part of the heptad repeat 2 (HR2) domain which might have plausible inhibitory effects on virus fusion. Taken together, this study discovered novel epitopes that might have important implications in the development of potential SARS-CoV-2 spike-based vaccine and therapeutics.
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http://dx.doi.org/10.3389/fimmu.2021.613045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032902PMC
April 2021

An unusual left ventricular outflow tract mass in a patient with systemic lupus erythematosus.

Natl Med J India 2020 Jan-Feb;33(1):19-21

Department of Cardiology, Cardiothoracic Surgery and Pathology, Medanta - The Medicity, Sector 38, Gurgaon 122001, Haryana, India.

A 25-year-old female, with systemic lupus erythematosus and antiphospholipid antibody syndrome, presented with exertional dyspnoea. Echocardiography showed a large (2.0 cm × 1.1 cm), echogenic, heterogeneous mass in the left ventricular outflow tract, under the aortic valve, attached to the ventricular aspect of the anterior mitral leaflet. Tiny flagellar, frond-like structures were seen attached to the surface of the mass. There was mitral regurgitation. These echocardiographic features were suggestive of a papillary fibroelastoma, but the histopathology of the excised mass revealed it to be a thrombus, which was consistent with a diagnosis of non-bacterial thrombotic endocarditis (NBTE). This case represents a rare histopathologically confirmed NBTE presenting as an unusually large mass in the left ventricular outflow tract.
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http://dx.doi.org/10.4103/0970-258X.308236DOI Listing
October 2021

Left Ventricular Thrombus and Cardioembolic Stroke in a Patient with Ulcerative Colitis: A Case Report.

Saudi J Med Med Sci 2021 Jan-Apr;9(1):67-70. Epub 2020 Dec 26.

Department of Laboratory Medicine, Pathology and Blood Bank, Medanta-The Medicity, Gurgaon, Haryana, India.

Left ventricular (LV) thrombi usually occur in the setting of global or regional LV systolic dysfunction and are extremely rare in the absence of LV wall motion abnormalities. We report here a case of a 23-year-old female who presented with cardioembolic stroke due to ulcerative colitis. To determine the cause of stroke, several investigations and evaluations were carried out, but the results were mostly normal or unremarkable. Transthoracic echocardiography revealed an oscillating pedunculated globular mass, which was eventually resected due to recurrent transient ischemic attacks. The histopathology of the excised mass revealed it to be an organized thrombus with acute and chronic inflammatory cells and fibroblasts. The uncommon etiology combined with the unusual appearance of the thrombus presented a major diagnostic and therapeutic dilemma for this exceedingly rare cause for intracardiac thrombus formation. Therefore, it would be useful to have a low threshold for screening patients with active inflammatory bowel disease for possible ventricular thrombosis before discharge, especially if other risk factors are present.
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http://dx.doi.org/10.4103/sjmms.sjmms_525_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839577PMC
December 2020

Predictors of Arterial Stiffness Amongst the 24-Hour Ambulatory Blood Pressure Variables in Hypertensive Patients.

Cureus 2020 Dec 21;12(12):e12207. Epub 2020 Dec 21.

Cardiology, Medanta Hospital, Gurgaon, IND.

Objective The objective of the study is to identify the predominant determinants of arterial stiffness as assessed by pulse-wave-velocity (PVW) amongst various 24-hour ambulatory blood pressure monitoring (ABPM) parameters in Indian hypertensive subjects. Method Subjects of both genders between 18-60 years with hypertension and who were either drug naïve or on stable anti-hypertensive treatment for at least three months were included in the study. All subjects underwent clinical evaluation with a medical history, biochemical investigations, and assessment of arterial stiffness by PWV along with 24-hour ABPM. Results We found the males were younger than females amongst hypertensive cohort (41.53 ± 10.89 years vs. 52.2 ± 5.17 years, respectively; p=0.001) and had shorter duration of hypertension (41.42 ± 49.14 months vs. 87.8 ± 74.55 months, respectively; p=0.012) and had lower 24-hour average pulse pressure (aPP; 49.1 ± 7.8 mm Hg vs. 57.83 ± 8.92 mm Hg, respectively; p=0.001) at baseline. Younger people (<40-years) as compared to those >40-years of age had the lower carotid-femoral (cf) PWV (972.8 ± 125.0 cm/sec vs. 1165.0 ± 208.4 cm/sec, respectively; p=0.001) and average brachial-ankle (ba) PWV (1413.7 ± 160.4 cm/sec and 1640.0 ± 227.1 cm/sec, respectively; p=0.001). Bivariate analysis revealed that amongst all the 24-hour ABPM parameters, 24-hour aPP had the strongest correlation (r=0.414, p=0.003) with arterial stiffness as assessed by PWV. Also, statistically significant correlation was found in age group <40 years between cf-PWV and both 24-hour aPP (r=0.54, p=0.025) as well as night-time aPP (r=0.59, p=0.013) Conclusion We conclude that 24-hour aPP showed the strongest correlation with arterial stiffness parameters and best correlated with arterial stiffness variables amongst 24-hour ABPM parameters, especially amongst subjects <40 years of age. The pulsatile blood pressure (BP) was a better predictor of aortic PWV than the continuous part of BP.
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http://dx.doi.org/10.7759/cureus.12207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818675PMC
December 2020

Cardiovascular Disease and Diabetes in South Asians: The Twin Epidemic.

Curr Diabetes Rev 2021 ;17(9):e122820189512

Fortis-CDOC Hospital for Diabetes and Allied Sciences President, Diabetes Foundation (India), and President National Diabetes Obesity and Cholesterol Foundation (NDOC), India.

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http://dx.doi.org/10.2174/1573399817666201228121145DOI Listing
January 2021

Clinical outcomes of submassive pulmonary embolism thrombolysis-an Indian experience.

Egypt Heart J 2020 Dec 14;72(1):87. Epub 2020 Dec 14.

Medanta Heart Institute, Delhi, India.

Background: Acute pulmonary thromboembolism is the most dangerous presentation of venous thromboembolic disease. The role of thrombolysis in massive pulmonary embolism has been studied extensively, but the same is not there for submassive pulmonary embolism. This study is aimed at evaluating the effects of thrombolysis in acute submassive pulmonary embolism. This was a prospective, case-control, observational study. Patients presenting with acute submassive pulmonary embolism were divided into thrombolysis group and control group depending on whether they received thrombolysis plus anticoagulation or anticoagulation only, respectively.

Results: A total of 86 patients were included in the study. Forty-two patients were in the thrombolysis group, and 44 patients were in the control group. The mean ± SD age in the control and thrombolysis groups was 63.3 ± 14.7 and 56.4 ± 13.8 years, respectively. The two groups were well matched in sex distribution and associated comorbidities like COPD, active surgery, major trauma, and immobilization. On echocardiography, dilated RA/RV in pre-treatment vs. post-treatment was seen in 20 (45.5%) vs. 20 (45.5%) in the control group and 26 (61.9%) vs. 11 (26.2%) in the thrombolysis group. Similarly, RV systolic dysfunction in pre-treatment vs. post-treatment was seen in 24 (54.5%) vs. 21 (47.7%) in the control group and 22 (52.4%) vs. 8 (19.0%) in the thrombolysis group. Pulmonary artery pressure in pre-treatment vs. post-treatment was 64.4 ± 15.0 vs. 45.9 ± 9.9 mmHg in the control group and 68.3 ± 17.4 vs. 31.4 ± 6.9 mmHg in the thrombolysis group. In control vs. thrombolysis group, there were 5 vs. 1 death, 6 vs. 1 hemodynamic decompensation, and 6 vs. 1 patient needing mechanical ventilation.

Conclusion: Thrombolysis in submassive pulmonary embolism is associated with better right ventricular functions, lower pulmonary artery pressures, and comparable mortality rates.
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http://dx.doi.org/10.1186/s43044-020-00123-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736429PMC
December 2020

Aortic pulse wave velocity and its relationship with transaortic flow and gradients in patients with severe aortic stenosis undergoing aortic valve replacement.

Indian Heart J 2020 Sep - Oct;72(5):421-426. Epub 2020 Jun 27.

Department of Cardiology, Medanta-The Medicity, Gurgaon, India. Electronic address:

Background: Low-flow, low-gradient severe aortic stenosis (LFLGAS) is a common clinical entity and is associated with poor prognosis. Increased left ventricular (LV) afterload is one of the mechanisms contributing to low LV stroke volume index (SVi) in these patients. Aortic stiffness is an important determinant of LV afterload, but no previous study has evaluated its relationship with LVSVi in patients with AS.

Methods: Fifty-seven patients (mean age 66 ± 8 years, 71.9% men) with severe AS [aortic valve area (AVA) < 1.0 cm] undergoing aortic valve replacement (AVR) were included in this study. Echocardiographic parameters of AS were correlated with carotid-femoral pulse wave velocity (cfPWV), a measure of aortic stiffness, derived using PeriScope® device.

Results: Mean AVA was 0.63 ± 0.17 cm with mean and peak transvalvular gradient 56.5 ± 18.8 mmHg and 83.2 ± 25.2 mmHg, respectively. Nearly half (26 of 57, 45.6%) of the subjects had SVi <35 mL/m, indicative of low-flow severe AS. These subjects had lower AVA, lower aortic valve gradient, and LV ejection fraction. CfPWV was numerically lower in these subjects [median 1467 (interquartile range 978, 2259) vs 1588 (1106, 2167)] but the difference was not statistically significant (p = 0.66). However, when analyzed as a continuous variable, cfPWV had significant positive correlation with SVi (Pearson's r 0.268, p = 0.048) and mean aortic valve gradient (Pearson's r 0.274, p = 0.043).

Conclusions: In patients with severe AS undergoing AVR, aortic stiffness measured using cfPWV is not a determinant of low-flow state. Instead, an increasing cfPWV tends to be associated with increasing transvalvular flow and gradient in these patients.
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http://dx.doi.org/10.1016/j.ihj.2020.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670240PMC
May 2021

Statins and SARS-CoV-2 disease: Current concepts and possible benefits.

Diabetes Metab Syndr 2020 Nov-Dec;14(6):2063-2067. Epub 2020 Oct 23.

Department of Cardiology, Medanta- the Medicity, Gurgaon, India.

Background And Aims: Inflammation-mediated tissue injury is the major mechanism involved in the pathogenesis of coronavirus disease 2019 (COVID-2019), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Statins have well-established anti-inflammatory, anti-thrombotic and immuno-modulatory effects. They may also influence viral entry into human cells.

Methods: A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic.

Results: Statins interact with several different signaling pathways to exert their anti-inflammatory and vasculoprotective effects. They also variably affect cholesterol content of cell membranes and interfere with certain coronavirus enzymes involved in receptor-binding. Both these actions may influence SARS-CoV-2 entry into human cells. Statins also upregulate expression of angiotensin-converting enzyme 2 receptors on cell surfaces which may promote viral entry into the cells but at the same time, may minimize tissue injury through production of angiotensin [1-7]. The net impact of these different effects on COVID-19 pathogenesis is not clear. However, the retrospective clinical studies have shown that statin use is potentially associated with lower risk of developing severe illness and mortality and a faster time to recovery in patients with COVID-19.

Conclusions: Early observations suggest beneficial effect of statin use on the clinical outcomes in COVID-19. Prospective randomized studies as well as well-designed laboratory studies are required to confirm these observations and to elucidate the mechanisms of such benefits, if proven.
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http://dx.doi.org/10.1016/j.dsx.2020.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582042PMC
January 2021

Normative values of cardiac chamber dimensions and global longitudinal strain in Indians: the Indian Normative Data of Echocardiography Analyzed (INDEA) study.

Int J Cardiovasc Imaging 2021 Mar 12;37(3):871-880. Epub 2020 Oct 12.

Sengupta Hospital and Research Institute, Ravinagar Square, Nagpur, 440033, India.

Ethnic-specific normal reference ranges for various echocardiographic measurements are essential for accurate diagnostic interpretation and clinical decision-making. Unfortunately, such normative data for Indians is lacking. A total of 880 healthy volunteers (mean age 39.7 ± 12.3 years, 63.8% men) from six centers across different regions of India were enrolled in this study. Comprehensive transthoracic echocardiographic study was performed in all subjects, in accordance with the existing guideline recommendations. Cardiac chamber dimensions [Left ventricular (LV) end-diastolic diameter and volume; right ventricular (RV) basal diameter, left atrial volume] were obtained and indexed to body surface area. LV ejection fraction, LV global longitudinal strain (LVGLS) and measures of RV systolic function were also obtained. The subjects were divided into 3 age groups (35 years or less, 36-55 years and 56 years or above) for analysis. Age- and gender-specific reference values for various clinically relevant echocardiographic parameters were derived. Compared with women, men had larger cardiac chamber dimensions and volumes, but not when indexed. In contrast, the women had higher LV systolic function, but right ventricular systolic function was not different. The indexed LV volumes in our study were much smaller than those recommended in the American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) 2015 chamber quantification guidelines but were similar to those reported in the Indian patients included in the recent World Alliance Societies of Echocardiography (WASE) Normal Values Study. LVGLS was also comparable with the WASE data. INDEA study is the first, multi-centric study to provide normal echocardiographic references values for Indian adults. Our findings underscore the need to follow India-specific reference values, instead of those recommended by the ASE/EACVI, which are largely applicable to the western populations.
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http://dx.doi.org/10.1007/s10554-020-02060-8DOI Listing
March 2021

Cardiovascular Risk Calculators and their Applicability to South Asians.

Curr Diabetes Rev 2021 ;17(9):e100120186497

Clinical and Preventive Cardiology, Medanta- The Medicity, Gurgaon, Haryana, India.

Background: Estimation of absolute cardiovascular disease (CVD) risk and tailoring therapies according to the estimated risk is a fundamental concept in the primary prevention of CVD is assessed in this study. Numerous CVD risk scores are currently available for use in various populations but unfortunately, none exist for South Asians who have much higher CVD risk as compared to their western counterparts.

Methods: A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic.

Results: Various currently available CVD risk scores and their pros and cons are summarized. The studies performed in native as well as migrant South Asians evaluating the accuracy of these risk scores for estimation of CVD risk are also summarized. The findings of these studies have generally been inconsistent, but it appears that the British risk scores (e.g. QRISK versions) may be more accurate because of inclusion of migrant South Asians in the derivation of these risk scores. However, the lack of any prospective study precludes our ability to draw any firm conclusions. Finally, the potential solution to these challenges, including the role of recalibration and subclinical atherosclerosis imaging, is also discussed.

Conclusion: This review highlights the need to develop large, representative, prospectively followed databases of South Asians providing information on various CVD risk factors and their contribution to incident CVD. Such databases will not only allow the development of validated CVD risk scores for South Asians but will also enable application of machine-learning approaches to provide personalized solutions to CVD risk assessment and management in these populations.
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http://dx.doi.org/10.2174/1573399816999201001204020DOI Listing
November 2021

Design and characterization of a germ-line targeting soluble, native-like, trimeric HIV-1 Env lacking key glycans from the V1V2-loop.

Biochim Biophys Acta Gen Subj 2021 01 16;1865(1):129733. Epub 2020 Sep 16.

Infection and Immunity, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, India.

Background: The HIV-1 envelope glycoprotein (Env) is the primary target for broadly neutralizing antibodies (bNAbs) which can block infection. The current design strategy of soluble forms of Env in native-like trimeric conformation induces neutralizing antibodies with minimal breadth and potency. Extensive shielding by N-glycans on the surface of the HIV-1 Env acts as an immune evasion mechanism by restricting B cell recognition of conserved neutralizing determinants. An alternate approach is to design Env protein with glycan deletion to expose the protein surface.

Methods: A stable native-like trimeric Env with glycan holes at potentially immunogenic locations is expected to elicit better induction of germ-line B-cells due to exposure of the immunogenic regions. However, the extent and consequences of glycan removal from the trimer apex that form an important epitope is not explored. In this work, we have designed a construct with glycans deleted from the trimer apex of an Indian clade C origin Env that has previously been characterized for immunogenicity, to understand the impact of deglycosylation on the structural and functional integrity as well as on the antibody binding properties.

Results: The V1V2 glycan-deleted protein maintains native-like trimeric conformation with improved accessibility of the V1V2-directed germ-line antibodies. Furthermore, we showed that the protein binds specifically to quaternary conformation-dependent bnAbs but minimally to non-neutralizing antibodies.

Conclusions: This study provide an important design aspect of HIV-1 Env-based immunogens with glycan holes in the apex region that could be useful in eliciting apex directed antibodies in immunization studies.
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http://dx.doi.org/10.1016/j.bbagen.2020.129733DOI Listing
January 2021

Tetramerizing tGCN4 domain facilitates production of Influenza A H1N1 M2e higher order soluble oligomers that show enhanced immunogenicity .

J Biol Chem 2020 10 13;295(42):14352-14366. Epub 2020 Aug 13.

Infection and Immunology, Translational Health Science & Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana, Faridabad, India.

One strategy for the development of a next generation influenza vaccine centers upon using conserved domains of the virus to induce broader and long-lasting immune responses. The production of artificial proteins by mimicking native-like structures has shown to be a promising approach for vaccine design against diverse enveloped viruses. The amino terminus of influenza A virus matrix 2 ectodomain (M2e) is highly conserved among influenza subtypes, and previous studies have shown M2e-based vaccines are strongly immunogenic, making it an attractive target for further exploration. We hypothesized that stabilizing M2e protein in the mammalian system might influence the immunogenicity of M2e with the added advantage to robustly produce the large scale of proteins with native-like fold and hence can act as an efficient vaccine candidate. In this study, we created an engineered construct in which the amino terminus of M2e is linked to the tetramerizing domain tGCN4, expressed the construct in a mammalian system, and tested for immunogenicity in BALB/c mice. We have also constructed a stand-alone M2e construct (without tGCN4) and compared the protein expressed in mammalian cells and in using and methods. The mammalian-expressed protein was found to be more stable, more antigenic than the protein, and form higher-order oligomers. In an intramuscular protein priming and boosting regimen in mice, these proteins induced high titers of antibodies and elicited a mixed Th1/Th2 response. These results highlight the mammalian-expressed M2e soluble proteins as a promising vaccine development platform.
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http://dx.doi.org/10.1074/jbc.RA120.013233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573259PMC
October 2020

A comparison of cardiovascular risk scores in native and migrant South Asian populations.

SSM Popul Health 2020 Aug 11;11:100594. Epub 2020 May 11.

Freeman Hospital, Newcastle-upon-Tyne, UK.

Background: South Asians have increased cardiovascular risk burden but little data exists comparing cardiovascular (CV) risk models in migrant and native South Asians. Our retrospective cohort study in patients presenting with first acute myocardial infarction(MI) compares the predictive value of CV risk scores in native and UK migrant South Asians.

Methods: Retrospective cohort study of 80 UK-based patients of South Asian origin admitted with first presentation MI, excluding patients with known coronary artery disease. A retrospective 10-year CV risk was calculated for each patient using four cardiovascular risk models: Framingham Risk Score(Risk), World Health Organisation(Risk), American College of Cardiology/American Heart Association(ACC/AHA) (Risk), and 3Joint British Societies'(Risk). Our aim was to assess agreement between these risk scores and conduct comparative analysis with native South Asians.

Results: Risk identified the largest proportion of migrant South Asians as 'high risk' with 65% of subjects having an estimated >20% 10-year CV risk. Risk provided the lowest 10-year CV risk estimates for South Asian migrants, identifying 21.25% of the migrant cohort as >20% risk of major CV event. Comparative analysis with the native South Asian cohort demonstrated Risk as the risk model most likely to identify patients as 'high'(>20%) risk(55.9%; p = 0.224).

Conclusions: This study represents the first analysis of predictive cardiovascular risk scores comparing migrant and native South Asian populations. Significant variation between the CV risk scores were observed, leading to inaccuracies in patient cardiovascular risk estimation. Given the growing burden of cardiovascular disease in Asian countries and different population characteristics, we highlight the need for population specific CV disease risk models whilst providing stimulus for further large-scale prospective studies.
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http://dx.doi.org/10.1016/j.ssmph.2020.100594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322355PMC
August 2020

SAPIEN S3 valve deployment in the pulmonary position using the gore DrySeal sheath to protect the tricuspid valve.

Catheter Cardiovasc Interv 2020 11 30;96(6):1287-1293. Epub 2020 Jun 30.

Department of Pediatrics, Charles E. Mullins Cardiac Catheterization Laboratories, Texas Children's Hospital, and Lillie Frank Abercrombie Section of Cardiology, Baylor College of Medicine, Houston, Texas, USA.

Background: Tricuspid valve injury can occur during implantation of a SAPIEN valve in the pulmonary position. We describe our experience using a long Gore DrySeal (GDS) sheath to protect the tricuspid valve during advancement of the Commander delivery system.

Methods: Retrospective single center review of all patients who underwent placement of a SAPIEN valve in the right ventricular outflow tract between January 2016 and April 2020. Patients were divided into two groups: delivery of the valve using standard technique (Group I), and with the use of a GDS (Group II), for comparison.

Results: There were 48 patients in total: 25 in Group I and 23 in Group II. In Group II, the first 10 patients had a 29 mm S3 placed through a 26 French (Fr), 65 cm GDS. We then performed additional crimping of the S3 onto the balloon after the balloon catheter was withdrawn to position the valve on the balloon outside the body. Subsequently, seven had a 29 mm S3 placed through a 24 Fr GDS, and four had a 26 mm S3 placed through a 22 Fr GDS including one weighing 16 kg. Two had a 23 mm S3 placed through a 22Fr GDS as the 20Fr GDS was not available in our lab. Severe tricuspid valve injury occurred in 2/25 (8%) of Group I patients and 0/23 of Group II patients.

Conclusion: Use of a long GDS may protect the tricuspid valve from injury during implantation of the S3 valve in the pulmonary position, and is technically feasible in smaller patients.
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http://dx.doi.org/10.1002/ccd.29120DOI Listing
November 2020
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