Consensus Statement from India on the Renal Benefits of ARNi, SGLT-2i, and Bisoprolol in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective ß1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

N-acetyl-l-tryptophan (NAT) ameliorates radiation-induced cell death in murine macrophages J774A.1 via regulating redox homeostasis and mitochondrial dysfunction.

Ionizing radiation interacts with the immune system and induces molecular damage in the cellular milieu by generating reactive oxygen species (ROS) leading to cell death. The present study was performed to investigate the protective efficacy of N-acetyl-L-tryptophan (NAT) against gamma-radiation-induced cell death in murine macrophage J774A.1 cells. The radioprotective efficacy of NAT was evaluated in terms of cell survivability, effect on antioxidant enzyme activity, and free radicals inhibition. Radioprotective efficacy of NAT pretreatment to irradiated cells was assessed via cell cycle progression, mitochondrial membrane potential (MMP) perturbation, and apoptosis regulation using flow cytometry. Results of the study demonstrated significant radioprotective efficacy (>80%) of NAT in irradiated cells as estimated by sulforhodamine B (SRB), MTT, and clonogenic assay. Significant (p < 0.001) reduction in ROS, xanthine oxidase, and mitochondrial superoxide levels along with increment in catalase, glutathione-s-transferase, glutathione, and ATPase activities in NAT pretreated plus irradiated cells was observed as compared to the gamma-irradiated cells. Further, significant (p < 0.001) stabilization of MMP and reduction in apoptosis was also observed in NAT pretreated plus irradiated cells as compared to irradiated cells that not pretreated with NAT. The current study demonstrates that NAT pretreatment to irradiated cells protects against gamma radiation-induced cell death by reducing oxidative stress, stabilizing MMP, and inhibiting apoptosis. These observations conclusively highlight the potential of developing NAT as a prospective radioprotective agent upon further validation using in-depth preclinical assessment in cellular and animal models.

Role of Iron Therapy in Heart Failure: A Consensus Statement from India.

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ß-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Bivalirudin anticoagulation in neonates and infants undergoing cardiac surgery.

OBJECTIVES: To determine the dosage of bivalirudin as the anticoagulant for cardiac surgery in neonates and infants. DESIGN: Pilot study. SETTING: Tertiary-care hospital. PARTICIPANTS: Twenty-five neonates and infants with congenital heart disease (CHD) undergoing cardiac surgery. INTERVENTIONS: The children received a 1 mg/kg bivalirudin bolus followed by a 2.5 mg/kg/h infusion as the anticoagulant for cardiac surgery. The dose was adjusted subsequently to maintain an activated clotting time (ACT) >480 s. MEASUREMENTS AND MAIN RESULTS: The mean age and weight were 5.3 months and 5.2 kg, respectively. Out of the 25 children, 16 were cyanotic. Baseline rotational thromboelastometry (ROTEM) (Tem Innovations GmbH, Munich, Germany) analysis revealed an underlying coagulation defect across EXTEM, INTEM, FIBTEM, and ADPTEM parameters. The dose of anticoagulant required was 1 mg/kg, followed by a 2.2 ± 0.4 mg/kg/h infusion. Only 1 child required an additional bolus dose. The ACT remained elevated for 4 hours after discontinuation of infusion. The mean 24-h postoperative chest tube drainage was 92 ± 36 mL. Excessive bleeding occurred in 4 children, 1 of whom required re-exploration. The platelet count remained low for 5 days, and, postoperatively, the prothrombin time and activated partial thromboplastin time remained low for 2 days. CONCLUSIONS: Effective anticoagulation was achieved with bivalirudin in the neonates and infants undergoing cardiac surgery. The dose required to maintain an ACT >480 s was 1.0 mg/kg, followed by 2.2 ± 0.4 mg/kg/h. The ACT remained elevated for 4 h after the discontinuation of bivalirudin infusion, resulting in an increased chest-tube output in some patients. Randomized, controlled trials are needed to further evaluate the safety of bivalirudin in the neonates and infants with complex congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass.

Mesenchymal stem cells are prospective novel off-the-shelf wound management tools.

Chronic/non-healing cutaneous wounds pose a debilitating burden on patients and healthcare system. Presently, treatment modalities are rapidly shifting pace from conventional methods to advanced wound care involving cell-based therapies. Mesenchymal stem cells (MSCs) have come across as a prospective option due to its pleiotropic functions viz. non-immunogenicity, multipotency, multi-lineage plasticity and secretion of growth factors, cytokines, microRNAs (miRNA), exosomes, and microvesicles as part of their secretome for assisting wound healing. We outline the therapeutic role played by MSCs and its secretome in suppressing tissue inflammation, causing immunomodulation, aiding angiogenesis and assisting in scar-free wound healing. We further assess the mechanism of action by which MSCs contribute in manifesting tissue repair. The review flows ahead in exploring factors that influence healing behavior including effect of multiple donor sites, donor age and health status, tissue microenvironment, and in vitro expansion capability. Moving ahead, we overview the advancements achieved in extending the lifespan of cells upon implantation, influence of genetic modifications aimed at altering MSC cargo, and evaluating bioengineered matrix-assisted delivery methods toward faster healing in preclinical and clinical models. We also contribute toward highlighting the challenges faced in commercializing cell-based therapies as standard of care treatment regimens. Finally, we strongly advocate and highlight its application as a futuristic technology for revolutionizing tissue regeneration.

Advances and clinical challenges for translating nerve conduit technology from bench to bed side for peripheral nerve repair.

Injuries to the peripheral nervous system remain a large-scale clinical problem. These injuries often lead to loss of motor and/or sensory function that significantly affects patients' quality of life. The current neurosurgical approach for peripheral nerve repair involves autologous nerve transplantation, which often leads to clinical complications. The most pressing need is to increase the regenerative capacity of existing tubular constructs in the repair of large nerve gaps through development of tissue-engineered approaches that can surpass the performance of autografts. To fully realize the clinical potential of nerve conduit technology, there is a need to reconsider design strategies, biomaterial selection, fabrication techniques and the various potential modifications to optimize a conduit microenvironment that can best mimic the natural process of regeneration. In recent years, a significant progress has been made in the designing and functionality of bioengineered nerve conduits to bridge long peripheral nerve gaps in various animal models. However, translation of this work from lab to commercial scale has not been achieve. The current review summarizes recent advances in the development of tissue engineered nerve guidance conduits (NGCs) with regard to choice of material, novel fabrication methods, surface modifications and regenerative cues such as stem cells and growth factors to improve regeneration performance. Also, the current clinical potential and future perspectives to achieve therapeutic benefits of NGCs will be discussed in context of peripheral nerve regeneration.

Protection to immune system of mice by N-acetyl tryptophan glucoside (NATG) against gamma radiation induced immune suppression.

Immune system is a critical modulator of radiation-induced biological effects. In this study, we have assessed protective potential of N-acetyl tryptophan glucoside (NATG) pre-treatment in bone marrow of gamma radiation challenged mice. Isolated bone marrow cells were analysed for cell cycle progression by flow cytometry, while various pro-/anti-inflammatory cytokine profiles were performed by ELISA method. Overall radioprotective ability of NATG in ensuring protection against gamma radiation-induced damage was assessed by evaluating whole body survival analysis and haematological studies on 9 Gy irradiated mice with/without NATG pre-treatment. Results exhibited pre-treatment with 150 mg/kg b.wt oral administration of NATG as most effective against 9 Gy radiation exposure. Moreover, NATG showed non-interfering effect on cell cycle progression in pre-treated irradiated mice group when compared to radiation alone group. In addition, cytokine expression analysis indicated significant (p > 0.05) elevation in levels of IFN-γ, IL-2, IL-12, IL-13 and IL-17 in NATG pre-treated irradiated mice in comparison to radiation alone group. On the contrary, NATG pre-treatment was observed to alleviate levels of TNF-α and IL-10 significantly (p < 0.05) in radiated group as compared to only irradiated mice group. Furthermore, NATG pre-treatment to 9 Gy radiation exposed mice aided in restoring their haematological parameters in terms of haemoglobin counts, RBC counts, WBC counts, hematocrit levels, platelets and granulocyte levels in comparison to irradiated alone mice, thus enhancing their immune system and contributing towards a better survival against gamma radiation-induced deleterious effects. Conclusively, this study highlights the potential of NATG as a prospective radiation countermeasure agent against ionizing radiation-induced assaults to the immune system.

Comparison of grading of aortic stenosis between transthoracic and transesophageal echocardiography in adult patients undergoing elective aortic valve replacement surgeries: A prospective observational study.

Introduction: Intraoperative trans-esophageal echocardiography (TEE) has been found to underestimate severity of aortic stenosis (AS) compared to trans-thoracic echo (TTE). We conducted a prospective study comparing pre induction TTE and intra operative TEE grading of AS in patients posted for aortic valve replacement surgeries. Methods: Sixty patients with isolated AS who were undergoing aortic valve replacement were enrolled in our study. Baseline TTE was done and after induction of anesthesia, TEE was done. Mean gradient across aortic valve, peak jet velocity, aortic valve area (AVA) by continuity equation and dimensionless index (DI) were assessed in both. Results: Mean gradient decreased from 56.4 in TTE to 39.8 mm Hg in TEE leading to underestimation of AS in 74.5% of patients (P < 0.0). Mean of peak jet velocity also decreased from 500 in TTE to 386cm/s in TEE (P < 0.01). In 76 % of patients this led to reduction of AS grade from severe to moderate. Mean AVA was 0.67 cm2 in TTE and 0.69 cm2 in TEE. Though there was 0.02 cm2 increase, it was not statistically significant (P = 0.07). All the patients remained as severe AS in TEE. DI mean was 0.19 in both TTE and TEE (P = 0.14).It led to underestimation of severity in 6% of patients in TEE. Conclusion: Our study shows that AVA measurement by continuity equation and DI are reliable in grading aortic stenosis while performing intraoperative TEE. Mean gradient and jet velocity can be significantly reduced.

The KRAS-variant and its impact on normal breast epithelial cell biology.

MicroRNA (miRNA)-binding site variants in 3' untranslated regions (3'UTRs) are a novel class of germ-line, functional mutations, which are now recognized as powerful biomarkers of human cancer risk and biology. The first mutation discovered in this class is the KRAS-variant, a let-7-binding site mutation in the 3'UTR of the KRAS oncogene. The KRAS-variant predicts increased cancer risk for certain populations, is a predictive biomarker of cancer treatment response across cancer types, leads to conserved tumor biology and elevated AKT signaling in KRAS-variant patient tumors, and was recently found to predict elevated TGF-ß and immunosuppression in cancer patients. Based on the functional biology of the KRAS-variant in cancer patients, here we chose to investigate altered normal cellular biology in the presence of the KRAS-variant, through interrogation of an isogenic normal breast epithelial cell line model with and without the KRAS-variant. We find that KRAS-variant normal breast epithelial cells exhibit a mesenchymal phenotype, which appears to be due to numerous molecular changes, including miRNA dysregulation and autocrine pathway alterations, including elevated TGF-ß, resulting in ZEB and SNAIL upregulation. Our findings support the hypothesis that the KRAS-variant has a fundamental biological impact on normal cellular biology, that is conserved in these patients when they develop cancer.

Breast Cancer and miR-SNPs: The Importance of miR Germ-Line Genetics.

Recent studies in cancer diagnostics have identified microRNAs (miRNAs) as promising cancer biomarkers. Single nucleotide polymorphisms (SNPs) in miRNA binding sites, seed regions, and coding sequences can help predict breast cancer risk, aggressiveness, response to stimuli, and prognosis. This review also documents significant known miR-SNPs in miRNA biogenesis genes and their effects on gene regulation in breast cancer, taking into account the genetic background and ethnicity of the sampled populations. When applicable, miR-SNPs are evaluated in the context of other patient factors, including mutations, hormonal status, and demographics. Given the power of miR-SNPs to predict patient cancer risk, prognosis, and outcomes, further study of miR-SNPs is warranted to improve efforts towards personalized medicine.

Randomized Controlled Trial of Heparin Versus Bivalirudin Anticoagulation in Acyanotic Children Undergoing Open Heart Surgery.

OBJECTIVE: To determine the safety and efficacy of bivalirudin as an anticoagulant for pediatric open heart surgery (OHS) and to determine its appropriate dosage for this purpose. DESIGN: Prospective, randomized controlled trial. SETTING: Tertiary care hospital. PARTICIPANTS: Fifty acyanotic children aged 1-12 years undergoing OHS. INTERVENTIONS: The children were randomized to receive either 4 mg/kg of heparin (n = 25, group H) or 1 mg/kg of bivalirudin bolus followed by 2.5 mg/kg/h infusion (n = 25, group B) as the anticoagulant. The doses were adjusted to maintain activated clotting time (ACT) above 480 seconds. At the conclusion of surgery, protamine (1.3 mg/100 U of heparin) was administered to children in group H. MEASUREMENTS AND MAIN RESULTS: The children were comparable in both groups with regard to demographic characteristics. The mean age and weight were 51.5 months and 13.4 kg in group H, and 59.3 months and 13.4 kg in group B. The dose of anticoagulant required was 4.0 ± 0.2 mg/kg in group H and 1.7 ± 0.2 mg/kg followed by 3.0 ± 0.7 mg/kg/h infusion in group B (p < 0.001). One child in group H required an additional dose compared to 13 (54.2%) children in group B. Intraoperatively, the ACT achieved was higher in group H compared to group B (p < 0.05). The ACT returned to baseline value after protamine administration in group H, but it remained elevated for 2 hours after termination of cardiopulmonary bypass (CPB) in group B (p < 0.01). The ACT was higher in group B compared to group H for 6 hours after termination of CPB (p < 0.05). Heparin prolonged the onset of clotting, decreased the rate and strength of thrombus formation, and inhibited platelet function to a greater extent than bivalirudin on viscoelastic coagulation testing. The total duration of surgery was prolonged in group B. The postoperative chest tube drainage was similar in group B (4.9 mL/kg) as in group H (5.9 mL/kg) in spite of higher ACT. The transfusion requirements were similar. No adverse event occurred in any patient. CONCLUSION: Bivalirudin is a safe and effective anticoagulant for pediatric OHS. Though it is not suitable as a routine anticoagulant for this purpose, it may be used as a heparin alternative in instances when heparin cannot be used. The dose required to maintain ACT for more than 480 seconds was 1.7 ± 0.2 mg/kg followed by 3.0 ± 0.7 mg/kg/h infusion. The ACT remained elevated for 2 hours after stopping the infusion. Bivalirudin did not increase postoperative bleeding and transfusion requirement.

N-Acetyl-tryptophan glucoside (NATG) protects J774A.1 murine macrophages against gamma radiation-induced cell death by modulating oxidative stress.

Immune system is amongst the most radiosensitive system to radiation-induced cellular and molecular damage. Present study was focused on the evaluation of radioprotective efficacy of a novel secondary metabolite, N-acetyl tryptophan glucoside (NATG), isolated from a radioresistant bacterium Bacillus sp. INM-1 using murine macrophage J774A.1 cells experimental model. Radioprotective efficacy of NATG against radiation-induced DNA damage and apoptosis was estimated using phosphatidyl-serine-externalization Annexin V-PI and Comet assay analysis. Radiation-induced cell death is the outcome of oxidative stress caused by free radicals. Therefore, perturbations in antioxidant enzymes i.e., superoxide dismutase (SOD), catalase, glutathione-s-transferase (GST) and GSH activities in irradiated and NATG pre-treated irradiated J774A.1 cells were studied. Results of the present study demonstrated that NATG pre-treated (0.25 µg/ml) irradiated (20 Gy) cells showed significant (p < 0.05) reduction in apoptotic cells index at 4-48 h as compared to radiation alone cells. Comet assay exhibited significant protection to radiation-induced DNA damage in J774A.1 cells. Significantly shortened DNA tail length, increased % Head DNA contents and lower olive tail moment was observed in NATG pre-treated irradiated cells as compared to radiation alone cells. Further, significant increase in catalase (~ 3.9 fold), SOD (67.52%), GST (~ 1.9 fold), and GSH (~ 2.5 fold) levels was observed in irradiated cells pre-treated with NATG as compared to radiation-alone cells. In conclusion, current study suggested that NATG pre-treatment to irradiated cells enhanced antioxidant enzymes in cellular milieu that may contribute to reduce oxidative stress and decrease DNA damage which resulted to significant reduction in the cell death of irradiated macrophages.

In vitro stimulatory effect of N-acetyl tryptophan-glucopyranoside against gamma radiation induced immunosuppression.

Radiation-induced manifestations like free radical burst, oxidative damage and apoptosis leading to cell death. In present study, N-acetyl tryptophan glucopyranoside (NATG) was assessed for its immune-radioprotective activities using J774A.1 cells. Clonogenic cell survival, cell cycle progression and cytokines i.e. IFN-γ, TNF-α, IL-2, IL-10, IL-12, IL-13 and IL-17A expression were evaluated in irradiated and NATG pretreated cells using clonogenic formation ability, flow cytometry and ELISA assay. Results indicated that 0.25µg/ml NATG exhibited maximum radioprotection against gamma-radiation (2Gy) without intervening in cell cycle progression. NATG pretreated (-2 h) plus irradiated cells showed significant elevation in IFN-γ (∼38.2%), IL-17A (∼53.7%) and IL-12 (∼58.8%) expression as compared to only irradiated cells. Conversely, significant decrease in TNF-α (∼21.6%), IL-10 (∼31.2%), IL-2 (∼23.7%) and IL-13 expression (∼17.8%) were observed in NATG pretreated plus irradiated cells as compared to irradiated cells. Conclusively, NATG pretreatment to irradiated J774A.1 cells, stimulate Th1 while diminish Th2 cytokines that contributes to radioprotection.

Is endothelin gene polymorphism associated with postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting?

BACKGROUND: The mechanism of development of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) has not been clearly defined, and the involvement of multiple factors such as advanced age, withdrawal of ß-blockers, inadequate atrial protection, and electrolyte imbalance, particularly hypomagnesemia has been documented by several authors. Despite all the available pharmacologic prophylaxis, incidence of AF still remains high in this group of patients. This unexplained cause could be genetic inheritance of endothelin-1 (ET-1) gene which is thought to have a pro-arrhythmogenic effect. AIM: This study aims to investigate the relationship between plasma ET-1 concentrations, ET-1 gene polymorphisms in loci -1370 T/G, -134 (3A/4A) Ins/del, Lys198Asn (G/T), and occurrence of AF in patients undergoing CABG. METHODOLOGY: Ninety-eight nonrelated, nondiabetic patients over a period of 4 years undergoing routine CABG were selected for the present study. All patients were genotyped for three single nucleotide polymorphisms (SNPs) in loci -1370 T/G, -134 (3A/4A) Ins/del, and Lys198Asn (G/T) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using an ET immunoassay. RESULTS: Plasma ET-1 concentrations were higher in AF+ group (P = 0.001) as compared to AF- group. The allele frequencies between AF+ and AF- group were significantly different only with respect to the Lys198Asn (G/T) SNP of the ET-1 gene. CONCLUSION: The study described the possible correlation of polymorphism of ET gene in CABG population from India. The ET-1 gene might play a disease-modifying role in atrial fibrillation.

Coagulopathies in cyanotic cardiac patients: An analysis with three point - of - care testing devices (Thromboelastography, rotational thromboelastometry, and sonoclot analyzer).

INTRODUCTION: In the last few years, viscoelastic point-of-care (POC) coagulation devices such as thromboelastography (TEG), rotational thromboelastometry (ROTEM), and Sonoclot (SON) analyzer have been increasingly used in major surgeries for timely assessment and management of coagulopathies. The aim of the present study was to evaluate coagulation profile of cyanotic cardiac patients with TEG, ROTEM, and SON analyzer. In addition, we assessed the correlation of standard laboratory coagulation tests and postoperative chest drain output (CDO) with the parameters of POC testing devices. MATERIALS AND METHODS: Thirty-five patients of either gender, belonging to the American Society of Anesthesiologists Grade I-III, and undergoing elective cardiac surgery on cardiopulmonary bypass for cyanotic congenital heart disease were included in this study. To identify possible coagulation abnormalities, blood samples for TEG, ROTEM, SON, and standard laboratory coagulation were collected after induction of anesthesia. The correlations between variables were assessed using Pearson's correlation coefficient. P < 0.05 was considered statistically significant. RESULTS AND DISCUSSION: EXTEM clot time (CT) and clot formation time (CFT) were prolonged in 87% and 45% patients whereas INTEM CT and CFT were prolonged in 36% and 73% patients, respectively. FIBTEM maximum clot firmness (MCF) was decreased in 30% patients. We observed significant correlation between fibrinogen concentration and ROTEM FIBTEM MCF (r = 0.94, P < 0.001). The SON platelet function (SON PF) showed good correlation with platelet count (r = 0.85, P < 0.001). We also found significant correlation between preoperative FIBTEM MCF and CDO in first 4 postoperative hours (r = 0.49, P = 0.004) and 24 postoperative hours (r = 0.52, P = 0.005). Receiver operating characteristic analysis demonstrated that SON PF and TEG maximum amplitude are highly predictive of thrombocytopenia below 100 × 109/L (area under the curve [AUC] - 0.97 and 0.92, respectively), while FIBTEM-MCF is highly predictive of hypofibrinogenemia (fibrinogen <150 mg/dL (AUC, 0.99). CONCLUSION: Cyanotic cardiac patients have preoperative coagulation abnormalities in ROTEM, TEG, and SON parameters. ROTEM FIBTEM is highly predictive of hypofibrinogenemia while SON PF is highly predictive of thrombocytopenia. ROTEM FIBTEM can be studied as a marker of increased postoperative CDO.

N-acetyl tryptophan glucopyranoside (NATG) as a countermeasure against gamma radiation-induced immunosuppression in murine macrophage J774A.1 cells.

Radiation exposure to immune system induces imbalance in cytokines expression involved in Th1/Th2 homeostasis perturbations. In the present study, N-acetyl tryptophan glucoside (NATG), a bacterial secondary metabolite, was evaluated for its possible radioprotective potential to immune system using J774A.1 murine macrophages. In this study, expression of IFN-γ, TNF-α, IL-10, IL-2, IL-12, IL-13 and IL-17A cytokines was analyzed in irradiated and NATG pretreated cells using ELISA assay. Results of the study indicated that irradiated macrophages (NK-1R+ cells) pretreated with NATG showed higher (p < .05) survival at all observed time-intervals (2 h-48 h) as compared to irradiated (20Gy) cells that were not pretreated with NATG. However, NATG pretreatment to irradiated HEK293T cells (that did not express NK-1Receptor) did not provide significant survival, suggesting NK-1R involvement in NATG-mediated radioprotection. Cytokine expression analysis demonstrated that NATG pre-treated plus irradiated J774A.1 murine macrophages exhibited increased IFN-γ levels (∼90%) with significant decrease in TNF-α at 24h as compared to irradiated cells. Further, significant decrease (∼20%) in IL-10 and IL-2 (∼26%) levels was observed in irradiated macrophages pretreated with NATG as compared to only irradiated cells. A sharp improvement in IL-17A (∼92%) and IL-12 (∼116%) expression was observed in irradiated macrophages pretreated with NATG as compared to only irradiated cells. Hence, NATG pre-treatment to irradiated macrophages induced IFN-γ, IL-17A and IL-12 expression, but suppresses TNF-α, IL-10 and IL-2 expressions. Conclusively, NATG pretreatment overcomes radiation-induced Th2 immune response by improving Th1 responsive cytoprotective cytokines IFN-γ, IL-17A and IL-12 in irradiated macrophages possibly by NK-1R antagonistic mechanism, and thus contributes to radioprotection.