Later Brain Death Declaration Correlates to Favorable Donor Characteristics but Decreased Heart Acceptance.

BACKGROUND: With rates of potential donor heart discard as high as 66% nationally, quality improvement efforts must seek to optimize donor utilization. Whether the timing of donor brain death declaration (BDD) influences organ acceptance is understudied. The authors sought to characterize the impacts of time between donor hospital admission and BDD on heart utilization and posttransplant outcomes. METHODS: All potential heart donors and recipients in the United Network for Organ Sharing database were identified (2006-2021). Admission-to-BDD cohorts were: 1 to 2 d (n = 52 469), 3 to 4 d (n = 44 033), 5 to 7 d (n = 24 509), and 8 to 10 d (n = 8576). Donor clinical characteristics were compared between cohorts, and donor acceptance was assessed using multivariable binary logistic regression. Recipient posttransplant survival was assessed with the Kaplan-Meier method. RESULTS: Donor demographics and comorbidity profiles (diabetes and hypertension) were comparable across cohorts. Anoxia/overdose deaths were more common (10% > 21% > 24% > 18%, respectively) and cardiopulmonary resuscitation requirements were higher (37% > 52% > 58% > 47%) when BDD occurred longer after admission. Renal dysfunction (44% > 44% > 35% > 29%) and inotrope requirements (52% > 25% > 36% > 29%) were lower in the later BDD cohorts. Proportions of hepatic dysfunction (18%-21%) and left ventricular ejection fraction <50% (13%-16%) were clinically equivalent. Donor acceptance differed by admission-to-BDD cohort (36% [1-2 d], 34% [3-4 d], 30% [5-7 d], and 28% [8-10 d]). Admission-to-BDD >4 d was independently associated with lower odds of acceptance on multivariable analysis (odds ratio 0.79, P < 0.001). Recipients experienced equivalent posttransplant survival for all donor admission-to-BDD cohorts ( P = 0.999 adults and P = 0.260 pediatrics). CONCLUSIONS: Heart donors with later BDD were disproportionately discarded despite similar-to-favorable overall clinical profiles, resulting in nearly 3000 fewer transplants during the study. Increased utilization of donors with later BDD and "high-risk" characteristics (eg, anoxia/overdose, cardiopulmonary resuscitation requirement) can improve rates of transplantation without compromising outcomes.

Overly Selective Offer Acceptance is Associated With High Waitlist Mortality for the Most Ill Lung Transplant Candidates.

The demand for organs for lung transplantation (LTx) continues to outweigh supply. However, nearly 75% of donor lungs are never transplanted. LTx offer acceptance practices and the effects on waitlist/post-transplant outcomes by candidate clinical acuity are understudied. UNOS was used to identify all LTx candidates, donors, and offers from 2005 to 2019. Candidates were grouped by Lung Allocation Score (LAS; applicable post-2005, ages ≥12 years): LAS<40, 40-60, 61-80, and >80. Offer acceptance patterns, waitlist death/decompensation, and post-transplant survival (PTS) were compared. "Acceptable organ offers" were those from donors whose organs were accepted for transplantation. Approximately 3 million offers to 34,531 candidates were reviewed. Median waitlist durations were: 9 days-(LAS>80), 17 days-(LAS 61-80), 42 days-(LAS 40-60), 125 days-(LAS<40) (P < 0.001 between all). Per waitlist-day, offer rates were: total offers - 0.8/day-(LAS>80), 0.7/day-(LAS 61-80), 0.6/day-(LAS 40-60), 0.4/day-(LAS<40); acceptable offers - 0.34/day-(LAS>80), 0.32/day-(LAS 61-80), 0.24/day-(LAS 40-60), 0.15/day-(LAS<40) (both P < 0.001 between all LAS). Among patients who experienced waitlist mortality/decompensation, ≥1 acceptable offer was declined in 92% (3939/4270) of patients - 78% for LAS >80, 88% for LAS 61-80, 93% for LAS 40-60, and 96% for LAS <40. Thirty-day waitlist mortality/decompensation rates were: 46%-(LAS>80), 24%-(LAS 61-80), 5%-(LAS 40-60), <1%-(LAS<40) (P < 0.001 between all). PTS was equivalent between patients for whom the first/second offer vs later offers were accepted (all LAS P > 0.4). The first offers that LTx candidates receive (including acceptable organs) are declined for nearly all candidates. Healthier candidates can afford offer selectivity but more ill patients (LAS>60) cannot, experiencing exceedingly high 30-day waitlist mortality.

In silico approaches illustrate the evolutionary pattern and protein-small molecule interactions of quinolone synthase from Aegle marmelos Correa.

Quinolone synthase from Aegle marmelos (AmQNS) is a Rutacean-specific plant type III polyketide synthase that synthesizes quinolone, acridone, and benzalacetone with therapeutic potential. Simple architecture and broad substrate affinity of AmQNS make it as one of the target enzymes to produce novel structural scaffolds. Another unique feature of AmQNS despite its high similarity to acridone forming type III polyketide synthase from Citrus microcarpa is the variation in the product formation. Hence, to explore the characteristic features of AmQNS, an in-depth sequence and structure-based bioinformatics analyses were performed. Our studies indicated that AmQNS and its nearest homologs have evolved by a series of gene duplication events and strong purifying selection pressure constrains them in the evolutionary process. Additionally, some amino acid alterations were identified in the functionally important region(s), which can contribute to the functional divergence of the enzyme. Prediction of favorable amino acid substitutions will be advantageous in the metabolic engineering of AmQNS for the production of novel compounds. Furthermore, comparative modeling and docking studies were utilized to investigate the structural behavior and small molecule interaction pattern of AmQNS. The observations and results reported here are crucial for advancing our understanding of AmQNS's phylogenetic position, selection pressure, evolvability, interaction pattern and thus providing the foundation for further studies on the structural and reaction mechanism.

D-Dimer assay as a non invasive test for the diagnosis of left atrial Thrombi in Indian patients with Rheumatic MS.

BACKGROUND: Systemic embolism is a serious and sometime fatal complication of rheumatic MS. OBJECTIVE: We assessed the predictive power of D-Dimer level to predict occurrence of left atrial (LA) thrombi in patients with rheumatic mitral stenosis (MS). METHODS: D-dimer levels were analyzed for 24 patients with rheumatic MS with LA clot and 22 patients with rheumatic MS with no LA clot undergoing transeosophageal echocardiography. A level more than 4 µg/ml was taken as elevated to predict the presence of LA clot in the study groups. RESULTS: For a cut-off value of 4 µg/ml, sensitivity was 66.67 % and specificity 100 % for prediction of LA clot and AUC 0.710. A cut-off value of less than 1 µg/ml, sensitivity was 91.67 % and 87. 5 % negative predictive value for ruling out presence of LA clot and AUC 0.721. CONCLUSION: A higher value of D-dimer can predict the possible presence of a LA clot and very low value can predict absence of clot in patients with rheumatic MS.

Comparison of the various lipid ratios and indices for risk assessment in patients of myocardial infarction.

OBJECTIVES: Coronary artery disease (CAD) has emerged as the major cause of morbidity and mortality among Asian Indians in the recent past. The following study was undertaken to assess the predictive value of novel biomarkers of dyslipidemia for risk assessment for CAD in the Indian population. DESIGN AND METHODS: The study group comprised of 100 clinically assessed patients of myocardial infarction and 100 age and sex matched healthy controls. Apolipoprotein-A (Apo-AI) and Apolipoprotein-B (Apo-B) were estimated and small dense LDL was derived mathematically. RESULTS: The cases showed significantly high levels of total serum cholesterol, triglycerides, LDL cholesterol, Apo-B, sdLDL, and non-HDL cholesterol. On carrying out multivariate regression analysis, Lp(a)/HDL ratio emerged as the best determinant of CAD risk CONCLUSION: The above data clearly underlines the role of these novel biomarkers in the risk assessment for CAD in the Indian context.

Interaction between dyslipidaemia, oxidative stress and inflammatory response in patients with angiographically proven coronary artery disease.

INTRODUCTION: Coronary artery disease (CAD) is emerging as the biggest killer of the 21st century. A number of theories have been postulated to explain the aetiology of atherosclerosis. The present study attempts to elucidate the interaction, if any, between inflammation, oxidative stress and dyslipidaemia in CAD. METHODS: A total of 753 patients undergoing angiography were evaluated and 476 were included in the study. The parameters studied included complete lipid profile, and apolipoprotein B, ferritin and nitric oxide (NO) levels. Statistical analysis was carried out to determine the interrelationship between these parameters and the best predictor of CAD risk. Cut-off points were determined from the receiver operating characteristics curves, and the specificity, sensitivity, positive predictive value, negative predictive value, odds ratio and confidence intervals were calculated. RESULTS: The levels of the parameters studied increased with the stenotic state and a positive correlation was observed between ferritin, NO and apolipoprotein B. NO emerged as the most reliable predictor of CAD, with an area under the curve of 0.992 and sensitivity and specificity of 97 and 98%, respectively. CONCLUSION: Environmental and genetic risk factors for CAD interact in a highly complex manner to initiate the atherosclerotic process. These risk factors should be considered mutually inclusive, not exclusive when devising pharmacological interventions, as multi-factorial risk management is the cornerstone of CAD management.

Evolutionary Implications and Physicochemical Analyses of Selected Proteins of Type III Polyketide Synthase Family.

Type III polyketide synthases have a substantial role in the biosynthesis of various polyketides in plants and microorganisms. Comparative proteomic analysis of type III polyketide synthases showed evolutionarily and structurally related positions in a compilation of amino acid sequences from different families. Bacterial and fungal type III polyketide synthase proteins showed <50% similarity but in higher plants, it exhibited >80% among chalcone synthases and >70% in the case of non-chalcone synthases. In a consensus phylogenetic tree based on 1000 replicates; bacterial, fungal and plant proteins were clustered in separate groups. Proteins from bryophytes and pteridophytes grouped immediately near to the fungal cluster, demonstrated how evolutionary lineage has occurred among type III polyketide synthase proteins. Upon physicochemical analysis, it was observed that the proteins localized in the cytoplasm and were hydrophobic in nature. Molecular structural analysis revealed comparatively stable structure comprising of alpha helices and random coils as major structural components. It was found that there was a decline in the structural stability with active site mutation as prophesied by the in silico mutation studies.

Homocysteine, fibrinogen and lipid profile in children of young adults with coronary artery disease.

Plasma homocysteine (9.05 ± 4.78 vs 5.93 ± 1.46 umol/L, P<0.01), plasma fibrinogen (313.76 ± 80.02 vs 275.47 ± 53.77 mg/dL, P<0.01), serum total cholesterol (171.64 ± 35.48 vs 152.62 ± 25.40 mg/dL, P<0.01), serum LDL cholesterol (109.51 ± 36.93 vs 87.6 ± 21.6 mg/dL, P<0.01) and fasting blood sugar (99.89 ± 7.46 vs 90.29 ± 9.85 mg/dL, ;were significantly higher in children (n=45) of young adults (<45 y) with coronary artery disease as compared to control group (n=45). No significant correlation was found for plasma homocysteine level of children with that of their parents in either group, whereas significant correlation was found for plasma fibrinogen of children with their parents in both the groups.

Assessment of insulin resistance, dyslipidemia and inflammatory response in North Indian male patients with angiographically proven coronary artery disease.

AIM: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in the developed world and is rapidly assuming epidemic proportions in developing countries, including India. Extensive research has proven the role of multiple etiologies such as dyslipidemia, inflammation, endothelial dysfunction and insulin resistance in the pathogenesis of CAD. The following study was undertaken to determine a possible inter-relationship between insulin resistance, inflammation and dyslipidemia, which are important risk factors for CAD in the atherosclerosis-prone north Indian male population. METHODS: The present study was conducted in 100 patients of myocardial infarction diagnosed on electrocardiographic and biochemical criteria, who subsequently underwent coronary angiography and 100 age matched healthy controls. The parameters that were evaluated include lipid profile, hsCRP, apolipoprotein B, insulin levels and HOMA-IR. RESULTS: Significantly higher serum levels of cholesterol, triglycerides, LDL and apolipoprotein B was observed in the patients as compared to the controls. On further classification, the dyslipidemia was marked in the patients with triple vessel disease as compared to single and double vessel disease. Similar pattern was observed for insulin resistance and CRP. Upon plotting the ROC curves, hsCRP emerged as the strongest predictor for CAD followed by apolipoprotein B. A significantly positive correlation was discerned between apolipoprotein B, CRP and HOMA-IR. CONCLUSION: The present study illustrates interplay between insulin resistance, inflammation and dyslipidemia in the CAD prone north Indian population. It also highlights the superiority of hs CRP in risk stratification of patients with angiographically proven CAD.

Prevalence of metabolic syndrome in patients with angiographically proven coronary artery disease presenting to a tertiary care hospital in Delhi, India.

BACKGROUND: Coronary artery disease is fast emerging as the major concern for afflicting people across the globe. The Indian subcontinent is highly predisposed to this condition due to distinctive risk factor profile of this population. This fact has led to a condition where the current preventative and management protocols that have worked well in the non-Asian Indian Caucasian populations, have failed to bring about the anticipated control over the incidence and progression of CAD in Asian Indians. Metabolic syndrome has been identified as a major determinant of CAD in this population. MATERIALS AND METHODS: The prevalence of metabolic syndrome was determined in 431 patients undergoing coronary angiography through various diagnostic algorithms. The Asian modified diagnostic criteria were also implemented to estimate the metabolic syndrome prevalence in patients with different levels of stenosis. RESULTS: We observed a high incidence of metabolic syndrome in the patients with coronary artery disease. The prevalence of MS increased with increase in severity of coronary artery involvement. The IDF guideline with Asian modification was the most successful diagnostic algorithm. CONCLUSIONS: It is now imperative to acknowledge the unique pattern of CAD and risk factor profile prevalent among South Asians. This will facilitate more focused and individualized management protocols directed to this population. Metabolic syndrome is a major syndrome prevalent in this population. Hence, effective control of MS may help in reducing the morbidity and mortality due to CAD in a great way.

Potential biochemical markers for preterm labor: a pilot study in north India.

Preterm delivery is a major contributor for neonatal mortality. Intensive research is underway to establish a reliable biomarker that can ascertain the risk of preterm delivery in pregnant women. The aim of our study was to evaluate the role of various biochemical parameters as potential biomarker for risk assessment for preterm labor. Forty women presenting with preterm labor and 40 women who delivered at term were included in the study. Parameters that were evaluated include corticotrophin (ACTH), prolactin, thyroid stimulating hormone (TSH), ferritin and Alkaline Phosphatase (ALP). Serum ACTH, ferritin, ALP and Ferritin/Iron ratio were significantly higher in the subjects who delivered prematurely as compared to the controls. Comparison of sensitivity, specificity, likelihood ratio, positive and negative predictive values for different cut offs for ACTH, ferritin, ALP and ferritin/iron ratio was carried out. Ferritin emerged as the best marker with area under curve of 0.96 as compared to 0.88 for ACTH, 0.825 for ALP and 0.735 for ferritin/iron ratio. Our study establishes the superiority of ferritin as a predictive biomarker for preterm labor as compared to the rest of the parameters evaluated.

Kernel based machine learning algorithm for the efficient prediction of type III polyketide synthase family of proteins.

Type III Polyketide synthases (PKS) are family of proteins considered to have significant roles in the biosynthesis of various polyketides in plants, fungi and bacteria. As these proteins shows positive effects to human health, more researches are going on regarding this particular protein. Developing a tool to identify the probability of sequence being a type III polyketide synthase will minimize the time consumption and manpower efforts. In this approach, we have designed and implemented PKSIIIpred, a high performance prediction server for type III PKS where the classifier is Support Vector Machines (SVMs). Based on the limited training dataset, the tool efficiently predicts the type III PKS superfamily of proteins with high sensitivity and specificity. The PKSIIIpred is available at http://type3pks.in/prediction/. We expect that this tool may serve as a useful resource for type III PKS researchers. Currently work is being progressed for further betterment of prediction accuracy by including more sequence features in the training dataset.

Inflammation and dyslipidaemia: a possible interplay between established risk factors in North Indian males with coronary artery disease.

OBJECTIVES: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in the developed world and is rapidly assuming epidemic proportions in developing countries, including India. This has led to extensive research to determine the risk factors and the pathways that may predispose to the elevated risk of this disease. Important among them include lipoproteins, homocysteine, lipoprotein (a), pro-inflammatory cytokines and others. The following study was undertaken to determine a possible inter-relationship between inflammation and dyslipidaemia, which are important risk factors for CAD in the atherosclerosis-prone North Indian male population. METHODS: The study groups comprised 150 clinically assessed North Indian male patients with acute myocardial infarction (AMI), diagnosed on electrocardiographic and biochemical criteria, and 150 healthy controls. Apolipoprotein-AI (Apo-AI), apolipoprotein-B (Apo-B) and C-reactive protein (CRP) levels were estimated using kits based on the immunoturbidimetric assay from Randox, UK. Tumour necrosis factor-alpha (TNF-alpha) and lipoprotein (a) were assayed using commercially available ELISA kits from Diaclone Research, Belgium and Innogenetics, Belgium, respectively. RESULTS: The patients with AMI showed highly significant elevations in the levels of total serum cholesterol, triglycerides, LDL cholesterol, Apo-B and a significant decline in HDL cholesterol, compared with healthy controls. Significantly elevated serum levels of inflammatory markers, TNF-alpha and CRP were seen in patients with AMI, compared to the control subjects. A significantly positive correlation of TNF-alpha was observed with lipoprotein (a) in patients with CAD. CONCLUSION: The data clearly underlines a possible interplay between inflammation and dyslipidaemia in the pathogenesis of CAD in the Indian context. This insight into the aetiopathogenesis of CAD will prove highly beneficial for devising better preventive measures and pharmacological interventions for CAD.

Iron deficiency in Indian children with attention deficit hyperactivity disorder.

A case control study was conducted at the Child Development and Early Intervention Clinic to determine the body iron status of children with ADHD, and study the correlation between the body iron status and ADHD symptoms. Serum ferritin was measured in newly diagnosed cases with ADHD and compared with that of controls. Correlation was studied between serum ferritin levels and the severity of ADHD symptoms as determined by Conners Rating Scale. Serum ferritin was found to be significantly lower in children with ADHD (6.04 ± 3.85 ng/mL) as compared to controls (48.96 ± 41.64 ng/mL, P value < 0.001). There was a significant negative correlation between serum ferritin levels and oppositional subscore on Conners Rating Scale.

Turn Around Time (TAT) as a Benchmark of Laboratory Performance.

Laboratory analytical turnaround time is a reliable indicator of laboratory effectiveness. Our study aimed to evaluate laboratory analytical turnaround time in our laboratory and appraise the contribution of the different phases of analysis towards the same. The turn around time (TAT) for all the samples (both routine and emergency) for the outpatient and hospitalized patients were evaluated for one year. TAT was calculated from sample reception to report dispatch. The average TAT for the clinical biochemistry samples was 5.5 h for routine inpatient samples while the TAT for the outpatient samples was 24 h. The turnaround time for stat samples was 1 h. Pre- and Post-analytical phases were found to contribute approximately 75% to the total TAT. The TAT demonstrates the need for improvement in the pre- and post-analytical periods. We need to tread the middle path to perform optimally according to clinician expectations.

Modification of Jaffe's kinetic method decreases bilirubin interference: A preliminary report.

The negative interference of bilirubin on serum creatinine determined by the kinetic alkaline picrate (Jaffe) reaction is the unresolved problem. Though high performance liquid chromatography and gas chromatography with mass spectroscopy have been proposed to be gold standards for creatinine estimation but they are not readily available in most of the clinical chemistry laboratories due to economic and technical constraints. Most of the present day analyzers use Jaffe's kinetic method without deproteinization. Though enzymatic methods are now routinely used as most accurate method but they are not acceptable due to cost constraints. Hence this study was planned to find out a possible solution to the problem of bilirubin interference by a minor modification in the commonly used Jaffe method so that it is amenable for use on the currently used analyzers.

Association between insulin resistance and hypothyroidism in females attending a tertiary care hospital.

The effect of thyroid status on insulin sensitivity is of great interest but despite various studies there is conflicting data on this subject. The study group comprised of 25 female subjects each with subclinical hypothyroidism, overt hypothyroidism and euthyroid controls. Serum samples of all the patients were assayed for thyroid profile, Insulin and lipid profile. Homeostasis model of assessment (HOMA-IR) was employed to assess the level of insulin resistance. Patients with hypothyroidism demonstrated insulin resistance and dyslipidemia as observed by the higher HOMA-IR and cholesterol and triglyceride levels respectively as compared to the controls. A significantly positive correlation between TSH and HOMA-IR level was also observed in the hypothyroidism group. Thyroid dysfunction leads to alterations in glucose and lipid metabolism which is an important risk factor for cardiovascular diseases. The dyslipidemia and insulin resistance should be managed aggressively to reduce the impending risk.

Paraoxonase: a multifaceted biomolecule.

BACKGROUND: Paraoxonase enzyme was first identified as a protective barrier against organophosphorus poisoning. After painstaking research spanning the last three decades, the knowledge about this enzyme has increased immensely. The present review attempts to elaborate the role of paraoxonase enzyme in normal physiology as well as provide an overview of the various disorders in which the enzyme may have a role in etiopathogenesis. METHODS: The literature was searched from the websites of the National Library of Medicine (http://www.ncbi.nlm.nih.gov/) and Pub Med Central, the U.S. National Library of Medicine's digital archive of life sciences journal literature. RESULTS: Paraoxonase acts as an important antioxidant enzyme against oxidative stress. The enzyme has been implicated in the pathogenesis of a number of disorders including cardiovascular disorders, cancers etc. CONCLUSIONS: A better understanding of the molecular mechanism of the enzyme along with the regulatory circuits will help us to utilize agonists to potentiate the anti oxidant actions of the enzyme.

Pre-analytical factors that influence the interpretation of prothrombin time in the clinical laboratory: one year experience in a super speciality hospital in India.

BACKGROUND: Accuracy and precision of Laboratory results is a top most priority in a clinical laboratory. Errors in Laboratory results could be due to pre-analytical, analytical and postanalytical variables. Here, we have discussed about pre-analytical variables during estimation of prothrombin time. METHODS: 15,335 PT (prothrombin time) samples received in the department of clinical biochemistry from June 2008 to May 2009 were evaluated for the prevalence of pre-analytical errors. The prothrombin time (PT) was analyzed on automated coagulometer-ACL 7000 with thromboplastin reagent supplied by Trinity Biotech, Ireland. RESULTS: Out of the 15,335 samples received in one year for analysis by the department, 464 samples showed the presence of pre-analytical variables and therefore, could not be assayed. Among the pre-analytical variables, inappropriate proportion between blood and anticoagulant was the most common error with a frequency of approximately 60%. Clotted samples and illegible handwriting accounted for another 15% each of the rejections respectively. Around 6% of the samples were hemolysed and another 2% were rejected due to lipemia. CONCLUSION: Appropriate knowledge of blood sample collection is a need of an hour to have accuracy in Laboratory results.