Publications by authors named "Saket Agarwal"

48 Publications

From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization.

Nucleic Acids Res 2022 Jun 23. Epub 2022 Jun 23.

Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA.

Preclinical mechanistic studies have pointed towards RNA interference-mediated off-target effects as a major driver of hepatotoxicity for GalNAc-siRNA conjugates. Here, we demonstrate that a single glycol nucleic acid or 2'-5'-RNA modification can substantially reduce small interfering RNA (siRNA) seed-mediated binding to off-target transcripts while maintaining on-target activity. In siRNAs with established hepatotoxicity driven by off-target effects, these novel designs with seed-pairing destabilization, termed enhanced stabilization chemistry plus (ESC+), demonstrated a substantially improved therapeutic window in rats. In contrast, siRNAs thermally destabilized to a similar extent by the incorporation of multiple DNA nucleotides in the seed region showed little to no improvement in rat safety suggesting that factors in addition to global thermodynamics play a role in off-target mitigation. We utilized the ESC+ strategy to improve the safety of ALN-HBV, which exhibited dose-dependent, transient and asymptomatic alanine aminotransferase elevations in healthy volunteers. The redesigned ALN-HBV02 (VIR-2218) showed improved specificity with comparable on-target activity and the program was reintroduced into clinical development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkac539DOI Listing
June 2022

Expanding RNAi therapeutics to extrahepatic tissues with lipophilic conjugates.

Nat Biotechnol 2022 Jun 2. Epub 2022 Jun 2.

Alnylam Pharmaceuticals, Cambridge, MA, USA.

Therapeutics based on short interfering RNAs (siRNAs) delivered to hepatocytes have been approved, but new delivery solutions are needed to target additional organs. Here we show that conjugation of 2'-O-hexadecyl (C16) to siRNAs enables safe, potent and durable silencing in the central nervous system (CNS), eye and lung in rodents and non-human primates with broad cell type specificity. We show that intrathecally or intracerebroventricularly delivered C16-siRNAs were active across CNS regions and cell types, with sustained RNA interference (RNAi) activity for at least 3 months. Similarly, intravitreal administration to the eye or intranasal administration to the lung resulted in a potent and durable knockdown. The preclinical efficacy of an siRNA targeting the amyloid precursor protein was evaluated through intracerebroventricular dosing in a mouse model of Alzheimer's disease, resulting in amelioration of physiological and behavioral deficits. Altogether, C16 conjugation of siRNAs has the potential for safe therapeutic silencing of target genes outside the liver with infrequent dosing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41587-022-01334-xDOI Listing
June 2022

Leveraging microphysiological systems to address challenges encountered during development of oligonucleotide therapeutics.

ALTEX 2022 11;39(2):273–296. Epub 2021 Nov 11.

Vertex Pharmaceuticals, Boston, MA, USA.

Oligonucleotide therapeutics (ONTs) encompass classes of medicines that selectively target and potentially ameliorate previously untreatable and often rare diseases. Several unique classes of ONTs provide versatility, enabling direct modu­lation of gene expression by virtue of Watson-Crick base pairing or modulation of cell signaling through structural mimicry or interference with protein-receptor interactions. Due to a lack of suitable in vitro models capable of recapitulating or predicting in vivo effects of ONTs, their discovery and optimization has relied heavily on animal studies for predicting efficacy and safety in humans. Since ONTs often lack cross-species activity, animal models with genetic humanization and/or species-specific surrogate ONTs are often required. Human microphysiological systems (MPS) offer an oppor­tunity to reduce the use of animals and may enable evaluation of drug mechanisms, optimization of cell and tissue targeting ligands or delivery vehicles, and characterization of pharmacokinetics (PK), pharmacodynamics (PD), and safety of candidate ONTs. The lack of published examples for MPS applications with ONT demonstrates the need for a focused effort to characterize and build confidence in their utility. The goals of this review are to summarize the current landscape of ONTs and highlight potential opportunities and challenges for application of MPS during ONT discovery and development. In addition, this review aims to raise awareness with ONT drug developers and regulatory authorities on the potential impact of MPS with respect to characterizing pharmacology, ADME, and toxicity and to educate MPS platform developers on unique design attributes needed to fully appreciate MPS advantages in ONT development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14573/altex.2108241DOI Listing
April 2022

The Nonclinical Disposition and Pharmacokinetic/Pharmacodynamic Properties of -Acetylgalactosamine-Conjugated Small Interfering RNA Are Highly Predictable and Build Confidence in Translation to Human.

Drug Metab Dispos 2022 Jun 21;50(6):781-797. Epub 2021 Jun 21.

Alnylam Pharmaceuticals, Cambridge, Massachusetts.

Conjugation of oligonucleotide therapeutics, including small interfering RNAs (siRNAs) or antisense oligonucleotides, to -acetylgalactosamine (GalNAc) ligands has become the primary strategy for hepatocyte-targeted delivery, and with the recent approvals of GIVLAARI (givosiran) for the treatment of acute hepatic porphyria, OXLUMO (lumasiran) for the treatment of primary hyperoxaluria, and Leqvio (inclisiran) for the treatment of hypercholesterolemia, the technology has been well validated clinically. Although much knowledge has been gained over decades of development, there is a paucity of published literature on the drug metabolism and pharmacokinetic properties of GalNAc-siRNA. With this in mind, the goals of this minireview are to provide an aggregate analysis of these nonclinical absorption, distribution, metabolism, and excretion (ADME) data to build confidence on the translation of these properties to human. Upon subcutaneous administration, GalNAc-conjugated siRNAs are quickly distributed to the liver, resulting in plasma pharmacokinetic (PK) properties that reflect rapid elimination through asialoglycoprotein receptor-mediated uptake from circulation into hepatocytes. These studies confirm that liver PK, including half-life and, most importantly, siRNA levels in RNA-induced silencing complex in hepatocytes, are better predictors of pharmacodynamics (PD) than plasma PK. Several in vitro and in vivo nonclinical studies were conducted to characterize the ADME properties of GalNAc-conjugated siRNAs. These studies demonstrate that the PK/PD and ADME properties of GalNAc-conjugated siRNAs are highly conserved across species, are largely predictable, and can be accurately scaled to human, allowing us to identify efficacious and safe clinical dosing regimens in the absence of human liver PK profiles. SIGNIFICANCE STATEMENT: Several nonclinical ADME studies have been conducted in order to provide a comprehensive overview of the disposition and elimination of GalNAc-conjugated siRNAs and the pharmacokinetic/pharmacodynamic translation between species. These studies demonstrate that the ADME properties of GalNAc-conjugated siRNAs are well correlated and predictable across species, building confidence in the ability to extrapolate to human.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1124/dmd.121.000428DOI Listing
June 2022

Impact of Serum Proteins on the Uptake and RNAi Activity of GalNAc-Conjugated siRNAs.

Nucleic Acid Ther 2021 08 15;31(4):309-315. Epub 2021 Apr 15.

Early Development, Alnylam Pharmaceuticals, Inc., Cambridge, Massachusetts, USA.

Serum protein interactions are evaluated during the drug development process since they determine the free drug concentration in blood and thereby can influence the drug's pharmacokinetic and pharmacodynamic properties. While the impact of serum proteins on the disposition of small molecules is well understood, it is not yet well characterized for a new modality, RNA interference therapeutics. When administered systemically, small interfering RNAs (siRNAs) conjugated to the -acetylgalactosamine (GalNAc) ligand bind to proteins present in circulation. However, it is not known if these protein interactions may impact the GalNAc-conjugated siRNA uptake into hepatocytes mediated through the asialoglycoprotein receptor () and thereby influence the activity of GalNAc-conjugated siRNAs. In this study, we assess the impact of serum proteins on the uptake and activity of GalNAc-conjugated siRNAs in primary human hepatocytes. We found that a significant portion of the GalNAc-conjugated siRNAs is bound to serum proteins. However, -mediated uptake and activity of GalNAc-conjugated siRNAs were minimally impacted by the presence of serum relative to their uptake and activity in the absence of serum. Therefore, in contrast to small molecules, serum proteins are expected to have minimal impact on pharmacokinetic and pharmacodynamic properties of GalNAc-conjugated siRNAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/nat.2020.0919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377513PMC
August 2021

Safety evaluation of 2'-deoxy-2'-fluoro nucleotides in GalNAc-siRNA conjugates.

Nucleic Acids Res 2019 04;47(7):3306-3320

Alnylam Pharmaceuticals, Inc., Cambridge, MA 02142, USA.

For oligonucleotide therapeutics, chemical modifications of the sugar-phosphate backbone are frequently used to confer drug-like properties. Because 2'-deoxy-2'-fluoro (2'-F) nucleotides are not known to occur naturally, their safety profile was assessed when used in revusiran and ALN-TTRSC02, two short interfering RNAs (siRNAs), of the same sequence but different chemical modification pattern and metabolic stability, conjugated to an N-acetylgalactosamine (GalNAc) ligand for targeted delivery to hepatocytes. Exposure to 2'-F-monomer metabolites was low and transient in rats and humans. In vitro, 2'-F-nucleoside 5'-triphosphates were neither inhibitors nor preferred substrates for human polymerases, and no obligate or non-obligate chain termination was observed. Modest effects on cell viability and mitochondrial DNA were observed in vitro in a subset of cell types at high concentrations of 2'-F-nucleosides, typically not attained in vivo. No apparent functional impact on mitochondria and no significant accumulation of 2'-F-monomers were observed after weekly administration of two GalNAc-siRNA conjugates in rats for ∼2 years. Taken together, the results support the conclusion that 2'-F nucleotides can be safely applied for the design of metabolically stabilized therapeutic GalNAc-siRNAs with favorable potency and prolonged duration of activity allowing for low dose and infrequent dosing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkz140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468299PMC
April 2019

Pulmonary artery-to-left atrial fistula discovered after the closure of atrial septal defect: A rare clinical scenario.

Ann Pediatr Cardiol 2018 May-Aug;11(2):211-213

Department of Cardiology, G B Pant Hospital, New Delhi, India.

A case of the right pulmonary artery-to- left atrial fistula with atrial septal defect (ASD) is presented. The fistula was detected after the patient developed desaturation following surgical closure of the ASD. It was managed with a transcatheter (trans-RPA route) closure of the fistula using a 12-mm Amplatzer ventricular septal defect closure device.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/apc.APC_138_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963240PMC
June 2018

Discovery of a Novel Small-Molecule Modulator of C-X-C Chemokine Receptor Type 7 as a Treatment for Cardiac Fibrosis.

J Med Chem 2018 04 17;61(8):3685-3696. Epub 2018 Apr 17.

Pfizer Worldwide Research & Development , Cambridge , Massachusetts 02139 , United States.

C-X-C chemokine receptor type 7 (CXCR7) is involved in cardiac and immune pathophysiology. We report the discovery of a novel 1,4-diazepine CXCR7 modulator, demonstrating for the first time the role of pharmacological CXCR7 intervention in cardiac repair. Structure-activity-relationship (SAR) studies demonstrated that a net reduction in lipophilicity (log D) and an incorporation of saturated ring systems yielded compounds with good CXCR7 potencies and improvements in oxidative metabolic stability in human-liver microsomes (HLM). Tethering an ethylene amide further improved the selectivity profile (e.g., for compound 18, CXCR7 K = 13 nM, adrenergic α 1a K > 10 000 nM, and adrenergic β 2 K > 10 000 nM). The subcutaneous administration of 18 in mice led to a statistically significant increase in circulating concentrations of plasma stromal-cell-derived factor 1α (SDF-1α) of approximately 2-fold. Chronic dosing of compound 18 in a mouse model of isoproterenol-induced cardiac injury further resulted in a statistically significant reduction of cardiac fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.8b00190DOI Listing
April 2018

Tetralogy of Fallot with left ventricular clot.

J Card Surg 2018 Jan 14;33(1):47-49. Epub 2018 Jan 14.

Department of Cardiothoracic and Vascular Surgery, G. B Pant Institute of Postgraduate Medical Education and Research, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.13512DOI Listing
January 2018

Dysphagia Lusoria with a supracardiac total anomalous pulmonary venous connection.

J Card Surg 2017 Nov 1;32(11):724-726. Epub 2017 Oct 1.

Department of Radiodiagnosis and interventional radiology, Govind Ballabh Pant Institute Of Post Graduate Medical Education and Research, Delhi University, Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.13222DOI Listing
November 2017

Ubiquitin-specific Protease-7 Inhibition Impairs Tip60-dependent Foxp3+ T-regulatory Cell Function and Promotes Antitumor Immunity.

EBioMedicine 2016 Nov 15;13:99-112. Epub 2016 Oct 15.

Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3. Genetic or pharmacologic targeting of Usp7 impairs Foxp3+ Treg suppressive functions, while conventional T cell responses remain intact. As a result, pharmacologic inhibitors of Usp7 can limit tumor growth in immunocompetent mice, and promote the efficacy of antitumor vaccines and immune checkpoint therapy with anti-PD1 monoclonal antibody in murine models. Hence, pharmacologic therapy with Usp7 inhibitors may have an important role in future cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2016.10.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264272PMC
November 2016

Management of iatrogenic RV injury - RV packing and CPB through PTFE graft attached to femoral artery.

Ann Pediatr Cardiol 2015 Jan-Apr;8(1):53-5

Department of Cardiothoracic and Vascular Surgery, Govind Ballabh Pant Hospital, New Delhi, India.

Cardiac injuries during repeat sternotomy are rare. While undergoing debridement for chronic osteomyelitis (post arterial septal defect closure), a 4-year-old girl sustained significant right ventricular (RV) injury. Bleeding from the RV was controlled by packing the injury site, which helped in maintaining stable hemodynamics till arrangements were made for instituting cardiopulmonary bypass (CPB). Since the femoral artery was very small and unsuitable for direct cannulation, a polytetrafluoroethylene (PTFE) graft sutured end-to-side to the femoral artery was used for establishing CPB. The injury was successfully repaired.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0974-2069.149520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322403PMC
February 2015

Glycemic control in cardiac surgery: rationale and current evidence.

Ann Card Anaesth 2014 Jul-Sep;17(3):222-8

Department of Cardio-Vascular and Thoracic Surgery, Apollo Gleaneagles, Kolkata, West Bengal, India.

Studies in cardiac surgical patients have shown an association of hyperglycemia with increased incidences of sepsis, mediastinitis, prolonged mechanical ventilation, cardiac arrhythmias and longer intensive care and hospital stay. There is considerable controversy regarding appropriate glycemic management in these patients and in the definition of hyperglycemia and hypoglycemia or the blood sugar levels at which therapy should be initiated. There is also dilemma regarding the usage of "tight glycemic control" with studies showing conflicting evidences. Part of the controversy can be explained by the differing designs of these studies and the variable definitions of hyperglycemia and hypoglycemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0971-9784.135873DOI Listing
September 2015

Right aortic arch with isolation of the left innominate artery in a case of double chamber right ventricle and ventricular septal defect.

Ann Pediatr Cardiol 2014 May;7(2):148-51

Department of Cardio Thoracic and Vascular Surgery, Govind Ballabh Pant Hospital, New Delhi, India.

Herein, we report an unusual case of right aortic arch with isolation of the left innominate artery in a case of double chamber right ventricle with ventricular septal defect. The blood supply to the innominate artery was by a collateral arising from the descending aorta. The embryological development of this anomaly can be explained by the hypothetical double aortic arch model proposed by Edwards with interruption of the arch at two levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0974-2069.132500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070208PMC
May 2014

Bilateral pulmonary vein stenting through an unligated vertical vein in a postoperative case of TAPVC.

J Card Surg 2014 Sep 19;29(5):705-8. Epub 2014 Apr 19.

Department of Cardiology, GB Pant Hospital, New Delhi, India.

We present a case of obstructed supracardiac total anomalous connection (TAPVC) where the vertical vein was left open at surgery because of significant pulmonary artery hypertension. One month following surgery, the patient developed progressive pulmonary venous obstruction at the pulmonary vein-left atrial junction bilaterally. The pulmonary veins were stented using a technique where the unligated vertical vein was utilized to access left atrium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.12322DOI Listing
September 2014

Dysphagia Lusoria with atrial septal defect: Simultaneous repair through midline.

Ann Pediatr Cardiol 2014 Jan;7(1):58-60

Department of CTVS, GB Pant Hospital, New Delhi, India.

An aberrant right subclavian artery from the descending aorta is almost always reported as an isolated anomaly. We present the case of a four-year-old child with an anomalous origin of the right subclavian artery from the descending aorta, associated with an ostium secundum atrial septal defect. The patient underwent simultaneous repair of both the anomalies through median sternotomy, with implantation of the subclavian artery into the right common carotid artery. We believe that median sternotomy is the optimal surgical approach for the management of these lesions. Other operative approaches are also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0974-2069.126562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959066PMC
January 2014

Unexplained desaturation following a Glenn shunt.

Ann Card Anaesth 2014 Jan-Mar;17(1):74-5

Department of Cardiothoracic and Vascular Surgery, G. B. Pant Hospital, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0971-9784.124162DOI Listing
September 2014

Mediastinitis following pediatric cardiac surgery.

J Card Surg 2014 Jan 25;29(1):74-82. Epub 2013 Nov 25.

Department of Cardiothoracic and Vascular Surgery, G.B. Pant Hospital, New Delhi, India.

Background: Mediastinitis following pediatric cardiac surgery is associated with significantly high morbidity and mortality.

Method: In our review, 21 studies from 1986 to 2011 (12 retrospective studies, eight prospective studies, and a multi-institutional study) including 44,693 pediatric cardiac patients were analyzed.

Results And Conclusion: Younger age, malnutrition, preoperative respiratory tract infection, high American anesthesiology score, longer duration of surgery, prolonged ventilation, and ICU stay were definite risk factors for mediastinitis. Early primary closure over drains, vacuum-assisted closure, muscle flap, and omental flap remain the most frequently performed treatments for post-sternotomy mediastinitis. Vacuum-assisted closure has emerged as the technique of choice in recent years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.12243DOI Listing
January 2014

Unusual presence of two innominate veins in presence of bilateral superior vena cava.

Ann Thorac Surg 2013 Aug;96(2):e53

Department of Cardiothoracic and Vascular Surgery, G. B. Pant Hospital, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2013.04.086DOI Listing
August 2013

Single stage repair of tetralogy of fallot associated with left pulmonary artery sling and tracheal stenosis.

J Card Surg 2013 Sep 30;28(5):595-8. Epub 2013 Jul 30.

Department of Cardiovascular and Thoracic Surgery, G B Pant Hospital, New Delhi, India.

We report a rare case of tetralogy of Fallot (TOF) with left pulmonary artery (LPA) sling with tracheal stenosis. The patient underwent successful surgery in one stage involving intracardiac repair of TOF, LPA reimplantation and resection of tracheal stenosis with end-to-end anastomosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocs.12192DOI Listing
September 2013

Lung herniation into pericardial cavity: A case of partial congenital absence of right pericardium.

Ann Pediatr Cardiol 2012 Jul;5(2):213-4

Department of Cardiovascular and Thoracic Surgery, G. B. Pant Hospital, New Delhi, India.

Congenital absence of pericardium is rarely seen, often diagnosed intraoperatively during cardiac and thoracic surgeries. Left-sided pericardial defects are more common than right-sided ones. We present a case of an incidentally detected congenital absence of right pericardium with herniation of part of the right lung during ventricular septal defect closure surgery in a male child aged 4 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0974-2069.99633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487219PMC
July 2012

Anesthetic management of a child with nephrotic syndrome undergoing open heart surgery: report of a rare case.

Ann Card Anaesth 2012 Oct-Dec;15(4):305-8

Department of Anaesthesiology, Intensive Care and Cardiothoracic and Vascular Surgery, G.B. Pant Hospital, New Delhi, India.

The congenital nephrotic syndrome (NS) in infancy and childhood is an important entity but combination with acyanotic congenital heart disease is uncommon. Anesthesia in such cases is challenging because of associated problems like hypo-protienemia, anti-thrombin III deficiency, edema, hyperlipidemia, coagulopathy, cardiomyopathy, immunodeficiency, increased lung water etc. We describe anesthetic management of a patient with childhood NS and sinus venosus atrial septal defect (ASD) undergoing open heart surgery. We also suggest guidelines for safe conduct of anesthesia and CPB in such patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0971-9784.101868DOI Listing
June 2013

Sinus of Valsalva aneurysm with left anterior descending coronary aneurysm.

J Card Surg 2012 Sep;27(5):611

Department of Cardio-Thoracic & Vascular Surgery, G B Pant hospital, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1540-8191.2012.01512.xDOI Listing
September 2012

Anomalous origin of left common carotid artery from the ascending aorta in a case of tetralogy of fallot.

J Card Surg 2012 Nov 10;27(6):757. Epub 2012 Sep 10.

Department of Cardiovascular and Thoracic Surgery, G B Pant Hospital, Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1540-8191.2012.01523.xDOI Listing
November 2012

Left main coronary artery atresia with tetralogy of Fallot: a novel association.

J Thorac Cardiovasc Surg 2012 Sep 12;144(3):e87-9. Epub 2012 Apr 12.

Department of CTVS, G. B. Pant Hospital, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2012.03.037DOI Listing
September 2012

Surgical repair of a submitral aneurysm in a three-year-old child.

J Card Surg 2012 Mar;27(2):238-40

Department of Cardio Thoracic and Vascular Surgery, G. B. Pant Hospital, New Delhi, India.

Submitral aneurysm (SMA) is a rare anomaly occurring adjacent to the posterior leaflet of the mitral valve. It usually presents in young adults and it is uncommon in the pediatric age group. We report one case of SMA in a three-year-old child and its successful surgical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1540-8191.2012.01428.xDOI Listing
March 2012

Autograft mitral valve replacement: a new technique.

Thorac Cardiovasc Surg 2012 Jul 3;60(5):356-7. Epub 2012 Jan 3.

Department of Cardiothoracic and Vascular Surgery, G. B. Pant Hospital, New Delhi, India.

We describe a new technique wherein we have used the Ionescu Ross Wooler stent for housing the pulmonary autograft. We believe that this technique is easy and reproducible and offers many advantages over the previously described techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0031-1295579DOI Listing
July 2012

Supracardiac total anomalous pulmonary venous connection with severe rheumatic mitral valve disease.

J Card Surg 2011 Sep;26(5):526-8

Cardiothoracic & Vascular Surgery Anesthesia, G. B. Pant Hospital, New Delhi, India.

A rare association of supracardiac total anomalous pulmonary venous connection (TAPVC) along with severe rheumatic mitral regurgitation is presented. The patient, a 28-year-old female, underwent successful repair of the TAPVC along with pericardial patch closure of the atrial septal defect and replacement of the mitral valve with a mechanical prosthesis. 
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1540-8191.2011.01307.xDOI Listing
September 2011

Extensive local spread of rhabdomyosarcoma.

J Card Surg 2011 May 29;26(3):294. Epub 2010 Dec 29.

Department of Cardiothoracic & Vascular Surgery, G.B. Pant Hospital, New Delhi, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1540-8191.2010.01179.xDOI Listing
May 2011
-->