Micropropagation and elicited production of triterpenoid saponin glycosides and stigmasterol via precursor and elicitor feeding in Bacopa floribunda (R.Br.) Wettst.-A potential nootropic herb.

Bacopa floribunda (Family: Plantaginaceae) is used in folklore medicines for the management of cognitive dysfunction. It has nootropic, antiaging, anti-inflammatory, anti-cholinesterase, and antioxidant properties. We developed an efficient and reproducible protocol for in vitro propagation of B. floribunda using the nodal explants. We assessed the effects of Murashige and Skoog (MS) medium fortified with various plant growth regulatory substances (PGRs), a precursor, and elicitors and their optimal combinations on regeneration and production of total saponins, triterpenoid saponin glycosides (bacoside A3, bacopaside X, bacopaside II, and bacosaponin C), and stigmasterol content in in vitro grown biomass of B. floribunda. The growth of the shoots and roots was stimulated by MS + 2.0 mg/l BAP + 2.0 mg/l KIN and MS + 0.5 mg/l IAA + 0.5 mg/l IBA + 1.0 mg/l NAA, respectively. After 10 weeks of acclimatization, plantlets of B. floribunda had a survival rate of 95%. The highest total saponin content (35.95 ± 0.022 mg DE/g DW) was noted in the treatment of MS + 2.0 mg/l BAP + 1.5 µM SQ. Similarly, total triterpenoid saponin glycosides and stigmasterol were found maximum in biomass derived from MS + 2.0 mg/l BAP + 1.5 µM SQ and MS + 2.0 mg/l BAP, respectively. At the same treatments, bacoside A3 (1.01 ± 0.195 mg/g DW), bacopaside II (43.62 ± 0.657 mg/g DW), bacopaside X (1.23 ± 0.570 mg/g DW), bacosaponin C (0.19 ± 0.195 mg/g DW), and stigmasterol (7.69 ± 0.102 mg/g DW) were reported. The present findings will help to highlight B. floribunda as a potent memory-enhancing herb, and in future also, it could be a potential substitute to B. monnieri. The current work is the first to describe the micropropagation and the elicited production of bioactive metabolites from the in vitro grown biomass of B. floribunda. In addition, further research is needed on production of bioactives, their pharmacological effects, and the elicited production using callus, cell suspension, and hairy root cultures.

Coronavirus disease 2019 convalescent children: outcomes after congenital heart surgery.

BACKGROUND: Children with exposure to coronavirus disease 2019 in recent times (asymptomatic or symptomatic infection) approaching congenital heart surgery programme are in increasing numbers. Understanding outcomes of such children will help risk-stratify and guide optimisation prior to congenital heart surgery. OBJECTIVE: The objective of the present study was to determine whether convalescent coronavirus disease 2019 children undergoing congenital heart surgery have any worse mortality or post-operative outcomes. DESIGN: Consecutive children undergoing congenital heart surgery from Oct 2020 to May 2021 were enrolled after testing for reverse transcription-polymerase chain reaction or rapid antigen test and immunoglobulin G antibody prior to surgery. Convalescent coronavirus disease 2019 was defined in any asymptomatic patient positive for immunoglobulin G antibodies and negative for reverse transcription-polymerase chain reaction or rapid antigen test anytime 6 weeks prior to surgery. Control patients were negative for any of the three tests. Mortality and post-operative outcomes were compared among the groups. RESULTS: One thousand one hundred and twenty-nine consecutive congenital heart surgeries were stratified as convalescence and control. Coronavirus disease 2019 Convalescent (n = 349) and coronavirus disease 2019 control (n = 780) groups were comparable for all demographic and clinical factors except younger and smaller kids in control. Convalescent children had no higher mortality, ventilation duration, ICU and hospital stay, no higher support with extracorporeal membrane oxygenation, high flow nasal cannula, no higher need for re-intubations, re-admissions, and no higher infections as central line-associated bloodstream infection, sternal site infection, and ventilator-associated pneumonia on comparison with coronavirus disease 2019 control children. CONCLUSIONS: Convalescent coronavirus disease 2019 does not have any unfavourable outcomes as compared to coronavirus disease 2019 control children. Positive immunoglobulin G antibody screening prior to surgery is suggestive of convalescence and supports comparable outcomes on par with control peers.

Predictors of mortality in patients with severe COVID-19 pneumonia - a retrospective study.

INTRODUCTION: The novel coronavirus pandemic has caused significant mortality throughout the world. This study was done as there is scarce data on mortality predictors in severe COVID-19 pneumonia patients admitted to ICU in the Indian population. MATERIAL AND METHODS: A retrospective study was conducted on COVID-19 pneumonia patients admitted to tertiary care center during June-October 2020. The records of patients admitted to ICU were collected and data included demography, symptoms, comorbidites and vital parameters. Laboratory parameters included complete hemogram, random blood sugar, S.Ferritin, S.LDH, renal function test, liver function test. Treatment-associated information such as the use of remdesivir, timing of initiating rem-desivir after the symptom onset, the use of steroids, use of anticoagulants, use of HFNC, NIV, ventilator were collected. 30 days mortality data post-discharge was collected via telephonic interview. RESULTS: 4,012 confirmed cases of COVID-19 were admitted to hospital, of which 560 (13.95%) with severe pneumonia were included in the study. Mean age was 57.75 ± 13.96 years. The mortality rates were 54.64% among severe COVID-19 cases and 5% among mild to moderate COVID-19 cases. The Cox multinominal regression analysis identified SpO2/FiO2 < 400, age > 50 years, duration of symptom > 4 days, serum ferritin > 450 µg/L, respiratory rate > 23/min, the presence of comorbidities and non-usage of remdesivir were independently associated with increased mortality. Mortality rate at 30 days was 56.60%. CONCLUSION: Severe COVID-19 pneumonia is associated with very high mortality, especially in a resource-constrained setting. The use of remdesivir may have to be considered early in the course of disease to prevent excess mortality related to COVID-19.

Phytochemical Studies on Two Unexplored Endemic Medicinal Plants of India, Barleria terminalis and Calacanthus grandiflorus.

Barleria terminalis Nees and Calacanthus grandiflorus (Dalzell) Radlk. are endemic medicinal plants of the Western Ghats of India. The aim of the present research work was to investigate phytochemical profile, potent bioactives using RP-HPLC, LC-MS and GC-MS and to evaluate their bioactivities. Acetone was found to be the best extraction medium for separating phytochemicals. Similarly, acetone and methanol extracts exhibited potential antioxidant properties. Ethanol extract of B. terminalis stem showed potent acetylcholinesterase (AChE) (89.10 ± 0.26%) inhibitory activity. Inhibition of α-amylase (36.96 ± 2.96%) activity was observed the best in ethanol extract of B. terminalis leaves and α-glucosidase inhibitory activity (94.33 ± 0.73%) in ethanol extract of C. grandiflorus stem. RP-HPLC analysis confirmed the presence of several phenolic compounds (gallic acid, hydroxybenzoic acid, vanillic acid, chlorogenic acid and coumaric acid) and phenylethanoid glycoside (verbascoside). The highest phenolics content were observed in B. terminalis (GA (4.17 ± 0.002), HBA (3.88 ± 0.001), VA (4.54 ± 0.001), CHLA (0.55 ± 0.004) mg/g DW, respectively). Similarly, LC-MS and GC-MS revealed the presence of phenolics, glycosides, terpenes, steroids, fatty acids, etc. Moreover, positive correlation between studied phytochemicals and antioxidants was observed in principal component analysis. Based on the present investigation, we conclude that B. terminalis and C. grandiflorus can be further explored for their active principles particularly, phenylethanoid glycosides and iridoids and their use in drug industry for pharmaceutical purposes.

A survey of practices during cardiopulmonary bypass in India: An Indian association of cardiovascular and thoracic anesthesiologist endeavor.

Context: Cardiac anesthesiologists play a key role during the conduct of cardiopulmonary bypass (CPB). There are variations in the practice of CPB among extracorporeal technologists in India. Aims: The aim of this survey is to gather information on variations during the conduct of CPB in India. Settings and Design: This was an online conducted survey by Indian College of Cardiac Anaesthesia, which is the research and academic wing of the Indian Association of Cardiovascular Thoracic Anaesthesiologists. Subjects and Methods: Senior consultants heading cardiac anesthesia departments in both teaching and nonteaching centers (performing at least 15 cases a month) were contacted using an online questionnaire fielded using SurveyMonkey™ software. There were 33 questions focusing on institute information, perfusion practices, blood conservation on CPB; monitoring and anesthesia practices. Results: The response rate was 74.2% (187/252). Fifty-one (26%) centers were teaching centers; 18% centers performed more than 1000 cases annually. Crystalloid solution was the most common priming solution used. Twenty-three percent centers used corticosteroids routinely; methylprednisone was the most commonly used agent. The cardioplegia solution used by most responders was the one available commercially containing high potassium St. Thomas solution (55%), followed by Del Nido cardioplegia (33%). Majority of the responders used nasopharyngeal site to monitor intraoperative patient temperature. Antifibrinolytics were commonly used only in patients who were at high risk for bleeding by 51% of responders, while yet, another 39% used them routinely, and 11% never did. About 59% of the centers insist on only fresh blood (<7 days old) when blood transfusion was indicated. The facility to use vaporizer on CPB was available in 62% of the centers. All the teaching centers or high volume centers in India had access to transesophageal echocardiography probe and echo machine, with 51% using them routinely and 38% using them at least sometimes. Conclusions: There is a wide heterogeneity in CPB management protocols among various Indian cardiac surgery centers. The survey suggests that adherence to evidence-based and internationally accepted practices appears to be more prevalent in centers that have ongoing teaching programs and/or have high volumes, strengthening the need to devise guidelines by appropriate body to help bring in uniformity in CPB management to ensure patient safety and high quality of clinical care for best outcomes.

Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study - PRIME study.

OBJECTIVE: To assess the effectiveness, overall tolerability, and gastrointestinal (GI) tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg]) in symptomatic treatment of severe acute pain in physician's routine clinical practice. MATERIALS AND METHODS: In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18-60 years) with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at base-line, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. RESULTS: A total of 351 patients (mean age 44.2 years; male 43%; female 57%) were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (p<0.0001). The number of patients with severe intensity of pain reduced from 100% at baseline to 18.3% at day 2 and 6.96% at day 5. According to the patient assessment, 68.36% of patients reported tolerability as "very good to good", whereas according to physician's assessment, "very good to good" tolerability was reported in 68.27% of patients. Five (1.43 %) patients discontinued the study because of adverse drug reaction. Five patients developed nine GI-related events of moderate intensity. Two patients developed three adverse reactions (burning sensation in urine, giddiness, and urine retention) other than GI events. No serious adverse drug reactions were reported during the study period. CONCLUSION: Tramadol hydrochloride/diclofenac sodium is an effective and well-tolerated treatment in Indian patients with severe acute pain. Treatment with tramadol hydrochloride/diclofenac sodium provides significant pain relief on day 2 and maintained until day 5 without any serious adverse reactions.

Patient prosthesis mismatch after aortic valve replacement: An Indian perspective.

CONTEXT: Perioperative period. AIMS: Occurrence of PPM after AVR, factors associated with PPM, impact on mortality. SETTINGS AND DESIGN: Teritary Care Referral Cardiac Centre. MATERIALS AND METHODS: A retrospective analysis of AVR procedures at a single centre over 4 years was conducted. Demographic, echocardiographic and outcome data were collected from institute database. Rahimtoola criteria of indexed effective orifice area (iEOA) were used to stratify patients into PPM categories. Patients with and without PPM were compared for associated factors. STATISTICAL ANALYSIS USED: Independent t-test, chi-square test, logistic regression analysis, ROC-AUC, Youden index. RESULTS: 606 patients with complete data were analysed for PPM. The incidence of mild, moderate and severe PPM was 6.1% (37), 2.5% (15) and 0.5% (3) respectively. There was no impact of PPM on all-cause in-hospital mortality. PPM was observed more with Aortic Stenosis (AS) compared to Aortic Regurgitation (AR) as etiology. Aortic annulus indexed to BSA (iAA) had a very good predictive ability for PPM at <16mm/m 2 BSA. CONCLUSIONS: PPM has lower incidence after AVR in this Indian population and does not increase early mortality. Patients with AS and iAA<16mm/m2BSA should be cautiously dealt with to prevent PPM.

Weight-for-age standard score - distribution and effect on in-hospital mortality: A retrospective analysis in pediatric cardiac surgery.

OBJECTIVE: To study the distribution of weight for age standard score (Z score) in pediatric cardiac surgery and its effect on in-hospital mortality. INTRODUCTION: WHO recommends Standard Score (Z score) to quantify and describe anthropometric data. The distribution of weight for age Z score and its effect on mortality in congenital heart surgery has not been studied. METHODS: All patients of younger than 5 years who underwent cardiac surgery from July 2007 to June 2013, under single surgical unit at our institute were enrolled. Z score for weight for age was calculated. Patients were classified according to Z score and mortality across the classes was compared. Discrimination and calibration of the for Z score model was assessed. Improvement in predictability of mortality after addition of Z score to Aristotle Comprehensive Complexity (ACC) score was analyzed. RESULTS: The median Z score was -3.2 (Interquartile range -4.24 to -1.91] with weight (mean±SD) of 8.4 ± 3.38 kg. Overall mortality was 11.5%. 71% and 52.59% of patients had Z score < -2 and < -3 respectively. Lower Z score classes were associated with progressively increasing mortality. Z score as continuous variable was associated with O.R. of 0.622 (95% CI- 0.527 to 0.733, P < 0.0001) for in-hospital mortality and remained significant predictor even after adjusting for age, gender, bypass duration and ACC score. Addition of Z score to ACC score improved its predictability for in-hosptial mortality (δC - 0.0661 [95% CI - 0.017 to 0.0595, P = 0.0169], IDI- 3.83% [95% CI - 0.017 to 0.0595, P = 0.00042]). CONCLUSION: Z scores were lower in our cohort and were associated with in-hospital mortality. Addition of Z score to ACC score significantly improves predictive ability for in-hospital mortality.

Propensity-matched analysis of association between preoperative anemia and in-hospital mortality in cardiac surgical patients undergoing valvular heart surgeries.

INTRODUCTION: Anaemia is associated with increased post-operative morbidity and mortality. We retrospectively assess the relationship between preoperative anaemia and in-hospital mortality in valvular cardiac surgical population. MATERIALS AND METHODS: Data from consecutive adult patients who underwent valvular repair/ replacement at our institute from January 2010 to April 2014 were collected from hospital records. Anaemia was defined according to WHO criteria (hemoglobin <13g/dl for males and <12g/dl for females). 1:1 matching was done for anemic and non-anemic patients based on propensity for potentially confounding variables. Logistic regression was used to evaluate the relationship between anaemia and in-hospital mortality. MatchIt package for R software was used for propensity matching and SPSS 16.0.0 was used for statistical analysis. RESULTS: 2449 patients undergoing valvular surgery with or without coronary artery grafting were included. Anaemia was present in 37.1% (33.91% among males & 40.88% among females). Unadjusted OR for mortality was 1.6 in anemic group (95% Confidence Interval [95% CI] - 1.041-2.570; p=0.033). 1:1 matching was done on the basis of propensity score for anaemia (866 pairs). Balancing was confirmed using standardized differences. Anaemia had an OR of 1.8 for mortality (95% CI- 1.042 to 3.094, P=0.035). Hematocrit of < 20 on bypass was associated with higher mortality. CONCLUSION: Preoperative anaemia is an independent risk factor associated with in-hospital mortality in patients undergoing valvular heart surgery.

Pediatric cardiac catheterization procedure with dexmedetomidine sedation: radiographic airway patency assessment.

AIMS: The aim of the study was to measure airway patency objectively during dexmedetomidine sedation under radiographic guidance in spontaneously breathing pediatric patients scheduled for cardiac catheterization procedures. SUBJECTS AND METHODS: Thirty-five patients in the age group 5-10 years scheduled for cardiac catheterization procedures were enrolled. All study patients were given loading dose of dexmedetomidine at 1 mg/kg/min for 10 min and then maintenance dose of 1.5 mg/kg/h. Radiographic airway patency was assessed at the start of infusion (0 min) and after 30 min. Antero-posterior (AP) diameters were measured manually at the nasopharyngeal and retroglossal levels. Dynamic change in airway between inspiration and expiration was considered a measure of airway collapsibility. Patients were monitored for hemodynamics, recovery time and complications. STATISTICAL ANALYSIS: Student paired t-test was used for data analysis. P < 0.05 was considered significant. RESULTS: Minimum and maximum AP diameters were compared at 0 and 30 min. Nasopharyngeal level showed significant reduction in the minimum (6.27 ± 1.09 vs. 4.26 ± 1.03, P < 0.0001) and maximum (6.51 ± 1.14 vs. 5.99 ± 1.03, P < 0.0001) diameters. Similarly retroglossal level showed significant reduction in the minimum (6.98 ± 1.09 vs. 5.27 ± 1.15, P < 0.0001) and maximum (7.49 ± 1.22 vs. 6.92 ± 1.12, P < 0.0003) diameters. The degree of collapsibility was greater at 30 min than baseline ( P < 0.0001). There was a significant decrease in heart rate ( P < 0.0001), and the average recovery time was 39.86 ± 12.22 min. CONCLUSION: Even though airway patency was maintained in all children sedated with dexmedetomidine, there were significant reductions in the upper airway dimensions measured, so all precautions to manage the airway failure should be taken.

Predicting mortality after congenital heart surgeries: evaluation of the Aristotle and Risk Adjustement in Congenital Heart Surgery-1 risk prediction scoring systems: a retrospective single center analysis of 1150 patients.

AIMS AND OBJECTIVES: To validate Aristotle basic complexity and Aristotle comprehensive complexity (ABC and ACC) and risk adjustment in congenital heart surgery-1 (RACHS-1) prediction models for in hospital mortality after surgery for congenital heart disease in a single surgical unit. MATERIALS AND METHODS: Patients younger than 18 years, who had undergone surgery for congenital heart diseases from July 2007 to July 2013 were enrolled. Scoring for ABC and ACC scoring and assigning to RACHS-1 categories were done retrospectively from retrieved case files. Discriminative power of scoring systems was assessed with area under curve (AUC) of receiver operating curves (ROC). Calibration (test for goodness of fit of the model) was measured with Hosmer-Lemeshow modification of χ2 test. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were applied to assess reclassification. RESULTS: A total of 1150 cases were assessed with an all-cause in-hospital mortality rate of 7.91%. When modeled for multivariate regression analysis, the ABC (χ2 = 8.24, P = 0.08), ACC (χ2 = 4.17 , P = 0.57) and RACHS-1 (χ2 = 2.13 , P = 0.14) scores showed good overall performance. The AUC was 0.677 with 95% confidence interval (CI) of 0.61-0.73 for ABC score, 0.704 (95% CI: 0.64-0.76) for ACC score and for RACHS-1 it was 0.607 (95%CI: 0.55-0.66). ACC had an improved predictability in comparison to RACHS-1 and ABC on analysis with NRI and IDI. CONCLUSIONS: ACC predicted mortality better than ABC and RCAHS-1 models. A national database will help in developing predictive models unique to our populations, till then, ACC scoring model can be used to analyze individual performances and compare with other institutes.

Repair of recurrent pseudoaneurysm of the mitral-aortic intervalvular fibrosa: role of transesophageal echocardiography.

Pseudoaneurysm of mitral-aortic intervalvular fibrosa (P-MAIVF) is a rare cardiac surgical condition. P-MAIVF commonly occurs as a complication of aortic and mitral valve replacement surgeries. The surgical trauma during replacement of the valves weakens the avascular mitral and aortic intervalvular area. We present a case of P-MAIVF recurrence 5 years after a primary repair. Congestive cardiac failure was the presenting feature with mitral and aortic regurgitation. In view of the recurrence, the surgical team planned for a double valve replacement. The sewing rings of the two prosthetic-valves were interposed to close the mouth of the pseudoaneurysm and to provide mechanical reinforcement of the MAIVF. Intra-operative transesophageal echocardiography (TEE) helped in delineating the anatomy, extent of the lesion, rupture of one of the pseudoaneurysm into left atrium and severity of the valvular regurgitation. Post-procedure TEE confirmed complete obliteration of the pseudoaneurysm and prosthetic valve function.

Efficacy of perioperative pregabalin in acute and chronic post-operative pain after off-pump coronary artery bypass surgery: a randomized, double-blind placebo controlled trial.

AIMS AND OBJECTIVES: We evaluated the efficacy of perioperative pregabalin on acute and chronic post-operative pain after off-pump coronary artery bypass (OPCAB) surgery. MATERIALS AND METHODS: Forty patients undergoing elective OPCAB surgery were randomized to pregabalin and control groups. Pregabalin group received 150 mg pregabalin 2 h prior to induction of anesthesia and 75 mg twice daily for 2 post-operative days whereas the control group received placebo at similar timings; pregabalin and placebo were administered by an anesthesiologist blinded to the drugs. Pain scores (visual analogue scale [VAS]) and sedation scores were observed at 0, 4, 6, 12, 24, 36 and 48 h after extubation. Time to extubation, tramadol consumption and side-effects were noted. VAS score was analyzed by Mann-Whitney U test. The analysis of variance test for repeated measures was used for comparison of the means of continuous variables. Group comparisons were made using the Chi-square-test. RESULTS: Pain-scores at 6, 12, 24 and 36 h from extubation at rest and at deep breath were less in pregabalin treated patients ( P < 0.05). Tramadol consumption was reduced by 60% in pregabalin group ( P < 0.001). Extent of sedation, extubation times and incidence of nausea were comparable. The effect on chronic post-operative pain was not significant. CONCLUSIONS: Perioperative pregabalin reduced pain scores at rest and deep breath and reduced consumption of tramadol in the post-operative period without delaying extubation and causing excessive sedation.

Transesophageal echocardiography in surgical management of pseudoaneurysm of mitral-aortic intervalvular fibrosa with aneurysms of right sinus of Valsalva and left main coronary artery.

Pseudoaneurysm of mitral-aortic intervalvular fibrosa (MAIVF) is a rare complication associated with aortic and/or mitral valve surgery complicated by infective endocarditis. We report pseudoaneurysm of MAIVF in a young adult without overt cardiac disease or previous cardiac surgery. The patient had a rare combination of pseudoaneurysm of MAIVF impinging on anterior mitral leaflet causing moderate mitral regurgitation, right sinus of Valsalva aneurysm extending into interventricular septum, and left main coronary artery aneurysm. Transesophageal echocardiography helped in confirming the lesions, delineating the anatomy of all the lesions, and assessing the adequacy of surgical repair.