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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 N-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 (ASGPR) 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, ASGPR-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.

Conjugation of oligonucleotide therapeutics, including small interfering ribonucleic acids (siRNAs) or antisense oligonucleotides (ASOs) to N-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, OXLUMOTM (lumasiran) for the treatment of primary hyperoxaluria, and Leqvio® (inclisiran) for the treatment of hypercholesterolemia, the technology has been well-validated clinically. While much knowledge has been gained over decades of development there is a paucity of published literature on the DMPK properties of GalNAc-siRNA. With this in mind the goals of this mini-review are to provide an aggregate analysis of these nonclinical 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 ASGPR-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 (RISC) in hepatocytes are better predictors of pharmacodynamics (PD) than plasma PK. Several in vitro and in vivo nonclinical studies were conducted to characterize the absorption, distribution, metabolism and excretion (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, 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 PK/PD 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.

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.

Introduction: Awareness about the use of antibiotics and its resistance is necessary to minimize the threat of emerging resistance. A questionnaire-based survey was conducted to analyse this knowledge among the studied population. Objectives: To bring awareness of antibiotics use, its disposal and to initiate medicine take-back program in the community. Materials and Methods: The present community-based descriptive, cross-sectional study with Mon purposive convenient sampling methods for sample collection performed on 650 families (2200 participants), from southwest Maharashtra population. The data was collected by giving questionnaires to the participants, related to antibiotics, its safety and disposal methods in English and local language designed by the author and confirmed by the institutional research committee. The data was analysed by descriptive analysis of all the variables to obtain frequency and percentage. Result: Ignorance about antibiotics and its resistance was seen in 76.9% population, 61.5% population believed antibiotics were harmless, 65.9% population continued the full course of antibiotics as prescribed, 81.4% population were not instructed by doctors about the hazards of not taking full course of antibiotics prescribed and 66.1% took antibiotics without prescription. 70.5% participants reported sharing antibiotics with others. Unawareness of antibiotics disposal was seen in 60% population who threw them in the trash as it is. Unused or unwanted medicines were collected by the investigator and either disposed of or reused (if in good condition) for needy patients. At the end of the visit, participants were instructed on proper use of antibiotics. Conclusion: The antibiotics knowledge in the studied population was low. Instructions were given to bring awareness regarding the use of antibiotics, its resistance and proper disposal. Keywords: Antibiotics, Resistance, Public health, Antimicrobial resistance, Questionnaire.

RNA interference (RNAi) therapeutics are a new class of medicines that can address unmet medical needs by silencing disease-causing gene transcripts. While delivery of short interfering RNAs (siRNAs) to hepatocytes has yielded multiple drug approvals, novel delivery solutions are needed to expand the reach of RNAi therapeutics. Here we report that conjugation of 2'-O-hexadecyl (C16) to siRNAs enables efficient silencing in the central nervous system (CNS), eye, and lung of multiple nonclinical species with broad cell type specificity. Intrathecally delivered C16-siRNAs are active across CNS regions and cell types, with sustained silencing for at least three months, which is an especially important outcome considering the challenging dosing route. Similarly, intravitreal and intranasal administration of C16-siRNAs resulted in potent and sustained knockdown in the eye and lung, respectively. Efficient delivery facilitated through C16 conjugation to optimized siRNA designs has enabled candidate selection for investigational human clinical trials assessing therapeutic silencing beyond the liver with infrequent (e.g. bi-annual) dosing.

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.

Generally, to make a campaign,startup, or any innovative idea successful requires some amount of donation. Fundraising or let us say Crowdfunding is an efficient way to raise money for your ideas, campaigns, startups etc. There are a lot of platforms available online and they provide space for setting up your own campaign so that you can gets funds for your campaign. people can go and contribute to any idea they like and get benefit from the pledge that you make. Certainly, there are lot of drawbacks to this model. There is no transparency and no assurance that your money is being put to the right use, there are charges to use the platform and many other issues. We try to over come these issues by making a fundraising platform using smart contract in solidity. This will be more secure as it uses Ethereum blockchain to make all the transactions and all the transactions are ethereum based. Not only this but the contributors have the right to vote for a transaction and only when a minimum consensus is achieved the requested transaction can be made.Contributors can have their own pool of contributors which can be achieved by multi-signature wallet.By creating a multisigned wallet , there will be two factor authentication mechanism to access funds, which are related more to security concerns. This not only enables a transparent transaction but also develops trust in the users of the platform. This not only resolves major drawbacks faced in the current live non blockchain based platforms like Kickstarter but also brings in more efficient platform to serve the purpose.”

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.

Conjugation of oligonucleotide therapeutics, including small interfering RNAs (siRNAs) or antisense oligonucleotides, to

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.

Background: Tetralogy of Fallot (TOF) is the most common congenital cyanotic heart disease (CCHD) in children. With the development and advancement of paediatric cardiac surgery and intensive care units, a large number of TOF are presenting for cardiac surgery. Operated TOF may suffer from endotracheal (ET) bleeding in postoperative period which results in delayed extubation of patients. ET bleeding is multifactorial with MAPCAs, coagulopathy residual VSD, and high LA pressure being usual causes. The objective of this study was to evaluate those children of TOF who suffered from ET bleeding, their causes and management after intracardiac repair.Methods: This was a single center retrospective study that included patients with a diagnosis of TOF. Total of 27 patients were operated at GB Pant Hospital, Department of CTVS from February 2021 to November 2021. After taking ethical approval we conducted a retrospective study to analyse the cause of endotracheal bleed. Statistical analyses were performed using STATA software version (16.0). Continuous variables were presented as mean±standard deviation (SD) or median (interquartile range [IQR]. Inclusion criteria was- all diagnosed case of tetralogy of fallot patient with age –1.5-8 years, both male and female. Exclusion criteria was- patients having co-morbidities, like juvenile diabetes, hypothyroidism, syndromic patients.Results: Endotracheal bleed noted in majority of patient in those MAPCAs were not coiled, not able to be ligated intaoperatively, they bleed in postoperative period which further delayed extubation of patients. Of the patients with Endotracheal bleed none had a residual cardiac defect. Post-operative mortality was 1/27.Conclusions: We hereby conclude that cause of endotracheal bleed after intracardiac repair of tetralogy of fallot patients can be due to left uncoiled, non- ligated major aorto-pulmonary collateral arteries (MAPCAs).

Primary left pulmonary vein stenosis is a very rare condition. It is associated with variable form of Pulmonary artery hypertension. Catheter based intervention is used to treat the disease like balloon dilation and stenting but this has high recurrence rate. Here is a case in which we did a sutureless repair of left pulmonary vein thus decreasing the possibility of recurrence. Sutureless surgical management is technically superior and less challenging than direct left atrial wall anastomosis and it provides better results than catheter based intervention in terms of recurrence of stenosis.

Atrial septal defect (ASD) is the fourth most common congenital heart disease in the world. It was treated with surgical closure with the help of CPB in the earlier days. Now there are two approaches available, open surgery under CPB and transcatheter closure. Here we are going to present late complication of transcatheter closure of ASD.

Airway management during tracheal surgery is always challenging for the anaesthesia team. Cardiopulmonary bypass (CPB) is generally not required during tracheal surgery on the cervical trachea. However, for tracheal surgeries CPB may be advantageous and give the surgeon more freedom to work. We report three cases of post-intubation tracheal stenosis successfully managed with tracheal resection and reconstruction performed under cardiopulmonary bypass.

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 Ki = 13 nM, adrenergic α 1a Kb > 10 000 nM, and adrenergic β 2 Kb > 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 st...

The approval of proteasome inhibitors bortezomib and carfilzomib and the E3 ligase antagonist thalidomide and its analogs, lenalidomide and pomalidomide, validates the ubiquitin-proteasome pathway as a source of novel drugs for treating cancer and, potentially, a variety of devastating illnesses, including inflammation, cardiovascular disease, and neurodegenerative disease. All elements of this critical regulatory pathway-the proteasome itself, E3 ligases (which conjugate ubiquitin to target proteins), and deubiquitylating enzymes (which deconjugate ubiquitin, reversing ligase action)-are potential therapeutic targets, and all have been worked on extensively during the past decade. No deubiquitylase inhibitors or activators have yet progressed to clinical trial, however, despite compelling target validation and several years of high-throughput screening and preclinical development of hits by numerous pharmaceutical companies, biotechnology organizations, and academic groups. The appropriateness of deubiquitylases as therapeutic targets in many disease areas is reviewed, followed by evidence that selective inhibitors of these cysteine proteases can be discovered. Because the lack of progress in drug-discovery efforts with deubiquitylases suggests a need for improved discovery methodologies, currently available platforms and strategies are analyzed, and improved or completely novel, unrelated approaches are considered in terms of their likelihood of producing clinically viable effectors of deubiquitylases.

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. doi: 10.1111/jocs.12322 (J Card Surg 2014;29:705–708)

Background: In India there is wide use of over the counter (OTC) antibiotics and unawareness of its harmful effects. In India dispensing antibiotics without prescription is a major contribution factor in development of antimicrobial resistance (AMR). The objectives of the present study were to evaluate awareness and proper use of OTC antibiotics in the community.Methods: Responses to a questionnaire covering various aspects on awareness and usage of OTC antibiotics were obtained from 100 families and 100 pharmacy shops in the community by second year MBBS students after permission from institutional ethical committee. The study period was from January 2019 to June 2019.Results: Among 100 responders 78% used OTC antibiotics for frequently reported illness like common cold (58%), body- ache (19%), fever (13%) and cough (10%). Most common reason for using OTC antibiotic is to avoid high consultation fees (64%).76% pharmacy dispense antibiotics without prescription. 60% pharmacy unaware of increase chance of developing resistance due to OTC antibiotics. 80% pharmacy maintain register book and were aware of laws and regulations of OTC prescription but still 70% dispense drugs due to fear of losing sales and profit. 50% pharmacy said they encourage patients to consult the physician and get the prescription. Most common antibiotic sold without prescription is amoxicillin (51%) and azithromycin (38%).Conclusions: We have identified unawareness among people about use and harmful effects of using OTC antibiotics. Also pharmacies are not following rules and regulations for OTC drugs. So our aim is to increase public knowledge of proper use and harmful effects of OTC antibiotics and help our global program to reduce AMR.

Coarctation of the aorta in an adult patient often requires extra-anatomic bypass techniques. Posterior pericardial bypass technique is one among the various techniques that has been described where a Dacron conduit is anastomosed between the lateral aspect of the ascending aorta and the descending thoracic aorta posterior to the pericardium. In the present patient, we describe an additional femoral artery canulation via a graft anastomosed end-to-side to the femoral artery to avoid spinal cord ischemia during the period that the descending aorta is clamped for anastomosis of the conduit.

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.

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. doi: 10.1111/jocs.12243 (J Card Surg 2014;29:74-82)

Introduction: In patients undergoing surgery for mitral valve replacement (MVR) for valvular heart disease, pulmonary artery hypertension (PAH) has been considered a major risk factor. In this prospective study, we have studied the early hemodynamic changes and post-operative outcomes of MVR among patients with severe PAH. Methods: 68 consecutive patients who underwent mitral valve replacement for severe rheumatic mitral valve disease with severe PAH (pulmonary artery pressure (PAP) > 50 mmHg) were studied prospectively for immediate postoperative hemodynamics and outcomes. The mean age of the patients was 32.1 years. 32 (47.05%) patients had mitral stenosis, 13 (19.11%) had mitral regurgitation and 23 (33.82%) had mixed lesions. Patients were divided into two groups based on preoperative pulmonary artery pressures. In 56 patients (82.35%, group I) PAP was sub-systemic or systemic, with a mean of 58.4 mmHg. Twelve patients (17.65%, group II) had supra-systemic PAP with a mean of 82.4 mmHg. Results: After mitral valve replacement, the PAP and pulmonary vascular resistance (PVR) decreased significantly in group I to near normal levels. In group II also the PAP and PVR decreased significantly but significant residual PAH remained. Operative mortality was 3.5% in group I and 16.6% in group II. Conclusions: MVR is safe and effective at the presence of severe PAH as long as the PAP is below or equal to systemic pressures. With suprasystemic PAP, MVR carries a high risk of mortality and the patient continues to have severe PAH in the postoperative period.

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., Highlights • Conditional deletion of Usp7 in Foxp3 + Treg cells causes rapidly lethal autoimmunity. • Pharmacologic inhibition of Usp7 impairs Treg but not conventional T cell function. • Usp7 targeting alone, or in conjunction with other therapies, promotes anti-tumor immunity. T-regulatory (Treg) cells are essential to regulation of the immune system, and are characterized by their expression of the transcription factor, Foxp3. Foxp3 is subject to ubiquitination and degradation via the proteasome. We now show that the deubiquitinase, Usp7, is a key regulator of Foxp3 + Treg biology through controlling levels of the histone acetyltransferase, Tip60 and, to a lesser extent, Foxp3. Gene deletion or pharmacologic inhibition of Usp7 impairs Treg but not conventional T cell functions. The pharmacologic targeting of Usp7 alone, or in conjunction with additional therapeutic strategies, is of significant benefit in promoting host anti-tumor immunity.

Prosthetic Valve Thrombosis (PVT) is a devastating complication of mechanical valve implantation. Treatment of PVT is usually by thrombolysis or by surgery. While the results of thrombolysis of thrombosed mitral valve is well established, results at the aortic position are not well reported. We sought to compare the results of thrombolytic therapy for thrombosed prosthetic bileaflet mechanical valve at the mitral and the aortic position. The data of 86 patients who had 94 episodes of PVT at the mitral or the aortic position, presenting between July 2001 to July 2010 at are institution were retrospectively reviewed. From July 2001 to July 2010, over a period of 120 months, 4,216 patients underwent mitral valve replacement, 2,496 had aortic valve replacement, and 532 had double valve replacement using the bileaflet ATS valve. After one thrombolytic therapy course in 86 patients, there was complete resolution of hemodynamic abnormalities in 46 patients (53.48%), partial resolution in 23 patients (26.74%), and no change in 10 patients (19.76%). In 9.30% of the cases, there was a recurrence with 62.5% full response to repeat thrombolysis. Full response to thrombolytic therapy was almost identical at both mitral and aortic position seen in about 53% of cases but whereas at mitral position partial response to thrombolytic therapy was seen in 18 patients (31%) but at aortic position only 5 patients (17%) had partial response to thrombolytic therapy . There was also a higher incidence of failure of thrombolytic therapy at aortic position, in 4 patients (28%) as against 6 patients (15%) at mitral position . Complications of thrombolytic therapy was more common with valve thrombosis at the aortic position. Thrombolytic therapy may be considered as first line of therapy in low risk patients . Those patients in NYHA III/IV, thrombolysis may still be used with almost 50% complete response to thrombolytic therapy and surgery can be avoided in them. Those patients who do not respond to thrombolytic therapy early should be considered for surgery especially in cases of PVT at aortic position.

Background Definitive palliation for complex cardiac anomalies with a functional single ventricle usually involves different modifications of Fontan operation/ Total Cavopulmonary Connection (TCPC). However, whether it should be done as one-stage procedure or two-stage procedure with initial bidirectional Glenn shunt remains an area of debate though many recent studies have shown benefit of two stage procedure particularly in high risk cases.

Background The decision to preserve the pulmonary valve during intracardiac repair of Tetralogy of Fallot [TOF] is traditionally based on the intra-operative measurement of pulmonary annulus by a Hegar dilator as per Rowlatt’s table. We sought to evaluate if there can be flexibility in not using a transannular patch repair in Indian population with mildly hypoplastic pulmonary annulus.

Despite numerous types of valve repairs currently being available for Ebstein’s anomaly, primary tricuspid valve replacement still hold its place in the surgical treatment of this disease, and is particularly valuable when the valve cannot be repaired for any reason. The purpose of the present study was to determine the current risk and the early and late results of bioprosthetic tricuspid valve replacement in Ebstein’s anomaly. 42 consecutive cases of Ebstein’s Anamoly who underwent tricuspid valve replacement with a bioprosthetic valve during the period of January 1991 to June 2007 were reviewed retrospectively to obtain early and late mortalities. Kaplan-Meier analyses were performed to estimate patient survival and freedom from valve degeneration. Mean age of patients was 11.76 yrs ± 4.56 yrs (range 6–22 yrs). Types of bioprosthetic valves implanted included Carpentier-Edwards (n = 12, 28.57%) and Hancock (n = 30, 71.43%) with valve size ranging from 21 to 33 mm (mean 28.3 ± 1.68 mm). Overall in-hospital mortality was 7.14% (n = 3, 2 females and 1 male). There was no early valve related complications in the present study. Follow up of 39 survived patients ranged from 1.5 years to 15 years with an average postoperative period of 7.1 yrs (median 6.5 years). There were 2 late deaths (5.13%). 2 patients (5.13%) had bioprosthetic valve degeneration during follow up (10.5 yrs and 14 after initial operations). Late survival among early survivor was found to be 96.6% at 5 yrs and 92.2% at 10 yrs and 15 yrs while freedom from bioprosthetic valve degeneration was estimated to be 91.7% at 5 yrs and 61.1% at 10 and 15 yrs. Valve replacement with a bioprosthesis produces good and long-lasting clinical improvement in patients with Ebstein’s anomaly and can be performed with acceptable mortality considering the very complex nature of the disease.

Background Right Ventricular Outflow Tract {RVOT} reconstruction using a conduit may be used in Tetralogy of Fallot patients who would otherwise require a trans-annular patch with the advantages of avoidance of free pulmonary regurgitation with its deleterious short and long term effects. Whereas an ideal conduit remains undefined, Contegra® bovine jugular vein bioprosthesis has been increasingly favored for this purpose worldwide. Present study summarizes the early and midterm outcome of Contegra bioprosthesis in RVOT reconstruction in patients of Tetralogy of Fallot (TOF).

Choice of heart valve in the developing countries is an unsettled issue due to illiteracy and noncompliance related increase in incidences of stuck valve and anticoagulant related bleeding and as such international guidelines may not be wholly applicable. The aim of our study was to compare outcomes after mitral, aortic or double valve replacements with mechanical versus bioprosthetic valves. Data of 503 patients who underwent cardiac valve replacement [300 mitral, 125 aortic, and 78 double valve] with either mechanical [bileaflet valve, n = 257] or biological [Hancock II, n = 246] valve from January 2003 to December 2008, were retrospectively analyzed. Specific outcomes assessed included incidences of valve thrombosis, systemic thromboembolism, anticoagulant related bleeding, structural valve dysfunction, prosthetic valve endocarditis, reoperation and death. Both the groups were comparable preoperatively except that patients receiving biological valve were more likely to be female and belonging to a rural setup. 30 day mortality was comparable in both groups. Incidences of valve related complications were significantly commoner in mechanical valve group. Two patients with mechanical valve required reoperation for stuck prosthetic valve at about 3 years after primary operation. There were two deaths in mechanical valve group, both related to stuck prosthetic valve. Prosthetic valve endocarditis was not reported in either group. At 5 years there was no incidence of structural valve dysfunction. Mechanical valves are associated with a significantly higher complication rate compared with biological valves in Indian patients. Biological valves thus maybe specifically suited to the Indian scenario. However, in choosing a prosthetic valve, patients’ involvement and informed consent should take the utmost importance.

Introduction Coronary Artery Disease (CAD) frequently coexists with Peripheral Vascular Disease (PVD) and poses management issues. When there is a concomitant infrarenal aortic occlusive disease, abdominal aorta is the traditional donor of bypass inflow to the lower limbs. However, the ascending aorta may also be used as the source of inflow to both the femoral and coronary arteries in patients who present with combined CAD and PVD. Here, 5 year follow up results of simultaneous off-pump coronary artery bypass grafting (OPCAB) and Ascending Aorto-Bifemoral Grafting [AABG] are presented and merits of the procedure are discussed.