GhTLP1, a thaumatin-like protein 1, improves Verticillium wilt resistance in cotton via JA, ABA and MAPK signaling pathway-plant pathways.

Verticillium wilt of cotton is a very serious soil-borne disease and there is no effective control method. The mechanism of Gossypium hirsutum thaumatin-like protein 1(GhTLP1) in upland cotton regulating Verticillium wilt resistance has been an uncovered research approach. GhTLP1 is mainly localized in the cell wall. Overexpression of GhTLP1 significantly enhanced Arabidopsis plants resistance to Verticillium dahliae, while its homologous mutant tlp1 in Arabidopsis was more susceptible to the pathogen, and the heterologous complement line (EC) recovered resistance to V. dahliae. GhTLP1 responds to jasmonate acid (JA) and abscisic acid (ABA) hormones and regulates mitogen-activated protein kinase (MAPK) signaling pathway-plant pathway to enhance Arabidopsis plants resistance to V. dahliae. Silencing GhTLP1 resulted decrease in cotton plants resistance to V. dahliae. Moreover, the mutation of GhTLP1 at site Tyr97 and Tyr199 with the phosphorylation also decreased plant resistance to V. dahliae. Therefore, GhTLP1 phosphorylation was observed important in cotton plants against V. dahliae. Further analysis demonstrated that GhTLP1 interacted with gossypium hirsutum laccase 14 (GhLAC14) to enhance plants resistance to V. dahliae. Silencing GhLAC14 resulted decrease in cotton plants resistance to V. dahliae. Here, we propose that GhTLP1 is a potential molecular target for improving resistance to Verticillium wilt in cotton.

Reduced racial disparity in receipt of optimal locoregional treatment for women with early-stage breast cancer.

INTRODUCTION: Racial disparities in breast cancer treatment contribute to Black women having the worst breast cancer survival rates in the U.S. We investigated whether differences in receipt of optimal locoregional treatment (OLT), defined as receipt of mastectomy, breast-conserving surgery, or no surgery when contraindicated, existed between Black and White women with early-stage breast cancer from 2008-2018. METHODS: In this retrospective cohort study, data from the Surveillance, Epidemiology, and End Results (SEER) Program Incidence Database was utilized to identify tumor cases from Black and White women aged 20-64 years old with stage I-II breast cancer. Logistic regression analyses were used to evaluate the associations between race and receipt of OLT as well as potential effect modification by tumor characteristics, and year of diagnosis. RESULTS: Among 177,234 women diagnosed with early-stage breast tumors, disparities in OLT between Black and White women were present from 2008-2010 (2008: 82.1% Black vs. 85.7% White, p<0.001; 2009: 82.1% Black vs. 85.8% White, p<0.001; 2010: 82.2% Black vs. 87.2% White, p<0.001). This disparity was eliminated between 2010-2011 (86.3% Black vs. 87.5% White, p = 0.15), and did not reoccur during the remainder of the study period. From 2010-2011, more Black women received radiation therapy following breast-conserving surgery (43.4% to 48.9%; p = 0.001), which accounted for an overall increased receipt of OLT. CONCLUSION: Increased receipt of radiation therapy with breast-conserving surgery appeared to drive a substantial increase in OLT for Black women from 2010-2011 that lasted throughout the study period. Further research on the underlying mechanisms that reduced this disparity is warranted.

Association between use of ß2-adrenergic receptor agonists and incidence of Parkinson's disease: Retrospective cohort analysis.

INTRODUCTION: Previous observational studies assessing ß2-agonist/-antagonist use on PD risk have yielded conflicting results. We evaluated the relationship between ß2-agonist use and the incidence of Parkinson's disease in patients with chronic lung disease. METHODS: We performed a retrospective cohort analysis on a 20% random sample abstracted from a traditional (fee-for-service) Medicare program in the United States. Inclusion criteria were individuals over 65 years old diagnosed with asthma, COPD, and/or bronchiectasis who were enrolled in a prescription drug (standalone Part D) plan over 2007-2010 and alive through 2014. The main outcome measure was a diagnosis of Parkinson's disease over the period 2011-2014, in relation to the number of 30-day-equivalent drug claims over 2007-2010. Logistic regression analysis was performed on a sample including 236,201 Medicare beneficiaries. RESULTS: The sample was 68% female, 80% white, and on average 77 years old as of 2010. Compared to non-users, ß2-agonist users were more likely to be younger (76.3y versus 78.0y), smokers (40.4% versus 31.1%) and asthmatic (62.4% versus 28.3%). The odds ratio for a ß2-agonist claim on PD development was 0.986 (95% CI 0.977-0.995) after adjusting for demographics, smoking history, respiratory exacerbations, comorbidities, and other drug use. Risk reductions were larger for males than females (0.974 versus 0.994, P = 0.032), and for individuals with COPD compared to those with asthma (0.968 versus 0.998, P = 0.049). Reverse causality was addressed with a Cox analysis that allowed ß2-agonist use to vary from medication initiation to disease onset. By the end of the follow-up period, ß2-agonist use was shown to be associated with a true protective effect against PD onset. DISCUSSION: ß2-agonist use is associated with decreased risk of PD incidence. Further investigation, possibly including clinical trials, is warranted to strengthen the evidence base supporting clinical decision-makers looking to repurpose pharmaceuticals to prevent neurodegenerative disease onset.

Flagellin C decreases the expression of the Gossypium hirsutum cation/proton exchanger 3 gene to promote calcium ion, hydrogen peroxide, and nitric oxide and synergistically regulate the resistance of cotton to Verticillium wilt.

To date, no ideal effective method for controlling Verticillium wilt in upland cotton (Gossypium hirsutum) has been defined. The purpose of this study was to determine the effects and mechanism through which flagellin C (FLiC) regulates the Gossypium hirsutum cation/proton exchanger 3 gene (GhCAX3), induces plant immunity, and increases resistance to Verticillium wilt. The FLiC gene was cloned from an endophytic bacterium (Pseudomonas) isolated from roots of the upland cotton cultivar Zhongmiansuo 41. The biocontrol effects of FLiC purified in vitro on resistant and susceptible upland cotton cultivars were 47.50 and 32.42%, respectively. FLiC induced a hypersensitive response (HR) in leaves of tobacco and immune responses in upland cotton. Transcriptome data showed that treatment with FLiC significantly enriched the calcium antiporter activity-associated disease-resistant metabolic pathway in seedlings. Moreover, FLiC downregulated GhCAX3 expression to increase intracellular calcium ion (Ca2+) content and stimulate increases in the intracellular hydrogen peroxide (H2O2) and nitric oxide (NO) contents. The coordinated regulation of Ca2+, H2O2, and NO enhanced cotton resistance to Verticillium wilt. Furthermore, transgenic Arabidopsis plants overexpressing FLiC showed significantly improved resistance to Verticillium wilt. FLiC may be used as a resistance gene and a regulator to improve resistance to Verticillium dahliae (VD) in upland cotton.

Time to think beyond door to balloon time: significance of total ischemic time in STEMI.

BACKGROUND: Significance of total ischemic time (TIT) in the context of ST-segment elevation myocardial infarction (STEMI) is still controversial. Therefore, in this study, we have evaluate the association of TIT with immediate outcomes in STEMI patients in whom recommended door to balloon (DTB) time of less than 90 min was achieved. RESULTS: A total of 5730 patients were included in this study, out of which 80.9% were male and median age was 55 [61-48] years. The median DTB was observed to be 60 [75-45] min and onset of chest pain to emergency room (ER) arrival time was 180 [300-120] min. Prolonged TIT was associated with poor pre-procedure thrombolysis in myocardial infarction (TIMI) flow grade (p = 0.022), number of diseased vessels (p = 0.002), use of intra-aortic balloon pump (p = 0.003), and in-hospital mortality (p = 0.002). Mortality rate was 4.5%, 5.7%, and 7.8% for the patients with TIT of ≤ 120 min, 121 to 240 min, and > 240 min, respectively. Thirty days' risk of mortality on TIMI score was 4.97 ± 7.09%, 5.01 ± 6.99%, and 7.12 ± 8.64% for the patients with TIT of ≤ 120 min, 121 to 240 min, and > 240 min, respectively. CONCLUSIONS: Prolonged total ischemic was associated with higher in-hospital mortality. Therefore, TIT can also be considered in the matrix of focus, along with DTB time and other clinical determinants to improve the survival from STEMI.

Genome-wide analysis of blood lipid metabolites in over 5000 South Asians reveals biological insights at cardiometabolic disease loci.

BACKGROUND: Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies. METHODS: We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci. RESULTS: We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci. CONCLUSIONS: Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.

Association between exenatide use and incidence of Alzheimer's disease.

INTRODUCTION: Recent developments suggest that insulin-sensitizing agents used to treat type II diabetes (T2DM) may also prove useful in reducing the risk of Alzheimer's disease (AD). The objective of this study is to analyze the association between exenatide use among Medicare beneficiaries with T2DM and the incidence of AD. METHODS: We performed a retrospective cohort analysis on claims data from a 20% random sample of Medicare beneficiaries with T2DM from 2007 to 2013 (n = 342,608). We compared rates of incident AD between 2009 and 2013 according to exenatide use in 2007-2008, measured by the number of 30-day-equivalent fills. We adjusted for demographics, comorbidities, and use of other drugs. Unmeasured confounding was assessed with an instrumental variables approach. RESULTS: The sample was mostly female (65%), White (76%), and 74 years old on average. Exenatide users were more likely to be male (38% vs. 35%), White (87% vs. 76%), and younger (by 4.2 years) than non-users. Each additional 30-day-equivalent claim was associated with a 2.4% relative reduction in incidence (odds ratio 0.976; 95% confidence interval 0.963-0.989; P < .001). There was no evidence of unmeasured confounding. DISCUSSION: Exenatide use is associated with a reduced incidence of AD among Medicare beneficiaries aged 65 years or older with T2DM. The association shown in this study warrants consideration by clinicians prescribing insulin sensitizing agents to patients.

Validity of the Stent Thrombosis Risk Score in Predicting Early Stent Thrombosis after Primary Percutaneous Coronary Intervention.

BACKGROUND: The thrombosis of the stent is one of the most important complications of percutaneous interventions, resulting in complete occlusion of the stented vessel. Aim of this study was to determine the validity of Stent Thrombosis Risk Score (STRS) in predicting early stent thrombosis (ST) after primary Percutaneous Coronary Intervention (PCI). METHODS: For this study, 569 consecutive patients undergone primary PCI from July 2018 to December 2018 were recruited. Early ST was defined as ST occurred during or within 30 days after the procedure. The STRS was calculated as proposed, developed, and validated in a past study. The receiver operating characteristic curve analysis was performed to determine the optimal cut-off value and area under the curve (AUC). RESULTS: A total of 569 patients were included, the median age was 56 [61-50] years. Early ST was observed in 33 (5.8%) patients. The median STRS was 4 [5-3] vs. 3 [4-2]; p = 0.009 for patients with and without Early ST respectively. STRS was found to be an independent predictor of early ST with an adjusted odds ratio of 1.41 (1.02-1.95). AUC was 0.631 and the optimal cut-off value was ≥5. Early ST rate was 3.3% at STRS of 0-2, which raised to 5.0% at STR of 3-4, and 17.2% at STRS of ≥5. CONCLUSIONS: In conclusion, STRS was found to be an independent predictor of early ST after primary PCI and has significant discriminating power. The rate of early stent thrombosis after primary PCI exponentially increased at STRS cut-off value of ≥5.

Angiographic characteristics and in hospital outcome of young patients, age up to 40 versus more than 40 years undergoing primary percutaneous coronary intervention.

OBJECTIVE: To compare angiographic characteristics and outcomes of primary percutaneous coronary intervention between young and old patients presenting with acute ST Elevation Myocardial Infarction. METHODS: The prospective observational study was conducted at the National Institute of Cardiovascular Diseases, Karachi, from December 17, 2016, to June 16, 2017, and comprised acute ST-Elevation Myocardial Infarction patients undergoing primary percutaneous coronary intervention (PCI). Data was collected on demographic, angiographic, and in-hospital outcomes. Those <40 years were considered young. Data was analysed using SPSS 21. RESULTS: Of the 415 patients, 50(12%) were young. Proportion of male was higher among the young (p=0.02) and so was the case with positive family history (p=0.002). The young had lesser cases of diabetes (p=0.028) and hypertension (p=0.034). Single vessel disease was more common among young (p<0.001). No significant difference was observed in post-procedure outcome related to age (p>0.05). CONCLUSIONS: Acute Myocardial Infarction in young was more likely associated with male gender, positive family history and less likely with hypertensive and diabetic status.

An Unbiased Lipid Phenotyping Approach To Study the Genetic Determinants of Lipids and Their Association with Coronary Heart Disease Risk Factors.

Direct infusion high-resolution mass spectrometry (DIHRMS) is a novel, high-throughput approach to rapidly and accurately profile hundreds of lipids in human serum without prior chromatography, facilitating in-depth lipid phenotyping for large epidemiological studies to reveal the detailed associations of individual lipids with coronary heart disease (CHD) risk factors. Intact lipid profiling by DIHRMS was performed on 5662 serum samples from healthy participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS). We developed a novel semi-targeted peak-picking algorithm to detect mass-to-charge ratios in positive and negative ionization modes. We analyzed lipid partial correlations, assessed the association of lipid principal components with established CHD risk factors and genetic variants, and examined differences between lipids for a common genetic polymorphism. The DIHRMS method provided information on 360 lipids (including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids), with a median coefficient of variation of 11.6% (range: 5.4-51.9). The lipids were highly correlated and exhibited a range of associations with clinical chemistry biomarkers and lifestyle factors. This platform can provide many novel insights into the effects of physiology and lifestyle on lipid metabolism, genetic determinants of lipids, and the relationship between individual lipids and CHD risk factors.

Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.

To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D-CHD analysis identified eight variants-two of which are coding-where T2D and CHD associations appear to colocalize, including a new joint T2D-CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.

Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity.

A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been shown to protect against coronary heart disease; we identified APOC3 homozygous pLoF carriers in our cohort. We recruited these human knockouts and challenged them with an oral fat load. Compared with family members lacking the mutation, individuals with APOC3 knocked out displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a 'human knockout project', a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.

Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: a mendelian randomisation analysis.

BACKGROUND: The lipoprotein(a) pathway is a causal factor in coronary heart disease. We used a genetic approach to distinguish the relevance of two distinct components of this pathway, apolipoprotein(a) isoform size and circulating lipoprotein(a) concentration, to coronary heart disease. METHODS: In this mendelian randomisation study, we measured lipoprotein(a) concentration and determined apolipoprotein(a) isoform size with a genetic method (kringle IV type 2 [KIV2] repeats in the LPA gene) and a serum-based electrophoretic assay in patients and controls (frequency matched for age and sex) from the Pakistan Risk of Myocardial Infarction Study (PROMIS). We calculated odds ratios (ORs) for myocardial infarction per 1-SD difference in either LPA KIV2 repeats or lipoprotein(a) concentration. In a genome-wide analysis of up to 17 503 participants in PROMIS, we identified genetic variants associated with either apolipoprotein(a) isoform size or lipoprotein(a) concentration. Using a mendelian randomisation study design and genetic data on 60 801 patients with coronary heart disease and 123 504 controls from the CARDIoGRAMplusC4D consortium, we calculated ORs for myocardial infarction with variants that produced similar differences in either apolipoprotein(a) isoform size in serum or lipoprotein(a) concentration. Finally, we compared phenotypic versus genotypic ORs to estimate whether apolipoprotein(a) isoform size, lipoprotein(a) concentration, or both were causally associated with coronary heart disease. FINDINGS: The PROMIS cohort included 9015 patients with acute myocardial infarction and 8629 matched controls. In participants for whom KIV2 repeat and lipoprotein(a) data were available, the OR for myocardial infarction was 0·93 (95% CI 0·90-0·97; p<0·0001) per 1-SD increment in LPA KIV2 repeats after adjustment for lipoprotein(a) concentration and conventional lipid concentrations. The OR for myocardial infarction was 1·10 (1·05-1·14; p<0·0001) per 1-SD increment in lipoprotein(a) concentration, after adjustment for LPA KIV2 repeats and conventional lipids. Genome-wide analysis identified rs2457564 as a variant associated with smaller apolipoprotein(a) isoform size, but not lipoprotein(a) concentration, and rs3777392 as a variant associated with lipoprotein(a) concentration, but not apolipoprotein(a) isoform size. In 60 801 patients with coronary heart disease and 123 504 controls, OR for myocardial infarction was 0·96 (0·94-0·98; p<0·0001) per 1-SD increment in apolipoprotein(a) protein isoform size in serum due to rs2457564, which was directionally concordant with the OR observed in PROMIS for a similar change. The OR for myocardial infarction was 1·27 (1·07-1·50; p=0·007) per 1-SD increment in lipoprotein(a) concentration due to rs3777392, which was directionally concordant with the OR observed for a similar change in PROMIS. INTERPRETATION: Human genetic data suggest that both smaller apolipoprotein(a) isoform size and increased lipoprotein(a) concentration are independent and causal risk factors for coronary heart disease. Lipoprotein(a)-lowering interventions could be preferentially effective in reducing the risk of coronary heart disease in individuals with smaller apolipoprotein(a) isoforms. FUNDING: British Heart Foundation, US National Institutes of Health, Fogarty International Center, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, and Pfizer.

Cost Differential of Chemotherapy for Solid Tumors.

PURPOSE: A significant portion of national cancer expenditure is attributed to chemotherapy.Although the National Comprehensive Cancer Network has generated recommendations for the treatment of various solid tumors, the outlined chemotherapeutic strategies lack information about the cost differential for increasing effectiveness. METHODS: Chemotherapy regimens (curative [adjuvant/neoadjuvant] and metastatic therapy) and dosages outlined in the 2013 National Comprehensive Cancer Network guidelines were acquired for four common cancers: bladder, breast, colon, and lung. Baseline drug and treatment costs (in US dollars)were calculated for the average US adult male on the basis of the payment allowance in the 2013 Medicare Part B average sales price (ASP) drug pricing files. Costs were extrapolated for a treatment period of 6 months. RESULTS: Of the 62 regimens included, the 6-month mean cost of chemotherapy was $26,989 ± $29,971, and the median cost was $9,611 (interquartile range, $6,305-$39,383). The mean cost of metastatic cancer therapy regimens (n = 32) was $35,315 ± 32,962 compared with $18,107 ± 23,873 for curative therapy (P = .02). Of the 13 regimens with biologics used, the mean costs were $77,278 versus $13,646 for 49 regimens that did not use biologics (P<.001). The cost differential between extremes of costs for regimens with presumed similar efficacy was $90,843 ($79,165 for curative therapy and $90,210 for metastatic cancer therapy). The highest cost differential was noted in breast cancer regimens at $71,041 for metastatic cancer therapy and $63,926 for curative therapy. CONCLUSION: A significant cost differential exists between chemotherapeutic regimens for the most common solid tumors. Incorporation of costs and incremental effectiveness in current guidelines may encourage socially responsible practice patterns.

Diagnostic laparoscopy should be performed before definitive resection for pancreatic cancer: a financial argument.

OBJECTIVES: Laparoscopy is recommended to detect radiographically occult metastases in patients with pancreatic cancer before curative resection. This study was conducted to test the hypothesis that diagnostic laparoscopy (DL) is cost-effective in patients undergoing curative resection with or without neoadjuvant therapy (NAT). METHODS: Decision tree modelling compared routine DL with exploratory laparotomy (ExLap) at the time of curative resection in resectable cancer treated with surgery first, (SF) and borderline resectable cancer treated with NAT. Costs (US$) from the payer's perspective, quality-adjusted life months (QALMs) and incremental cost-effectiveness ratios (ICERs) were calculated. Base case estimates and multi-way sensitivity analyses were performed. Willingness to pay (WtP) was US$4166/QALM (or US$50,000/quality-adjusted life year). RESULTS: Base case costs were US$34,921 for ExLap and US$33,442 for DL in SF patients, and US$39,633 for ExLap and US$39,713 for DL in NAT patients. Routine DL is the dominant (preferred) strategy in both treatment types: it allows for cost reductions of US$10,695/QALM in SF and US$4158/QALM in NAT patients. CONCLUSIONS: The present analysis supports the cost-effectiveness of routine DL before curative resection in pancreatic cancer patients treated with either SF or NAT.

Safety of primary percutaneous coronary intervention with and without (selective) thrombus aspiration.

OBJECTIVE: To determine the safety and efficacy of selective thrombus aspiration during Primary Percutaneous Coronary Intervention (PCI). METHODS: This observational prospective study was conducted in the catheterization laboratory of a tertiary care cardiovascular centre. A total of 150 consecutive patients who underwent primary PCI were enrolled. Aspiration was done only when thrombus burden was considered significant. After completion of procedure angiographic and electrocardiographic signs were recorded and clinical follow up was documented up to 1 year. RESULTS: No significant difference among the groups was found in age, height, weight and other risk factors like Hypertension, Diabetes Mellitus and Smoking. In general, left anterior descending artery was culprit in - 65% of patients and more than 90% of culprit vessels had visible thrombus. Multivessel disease was present in 38% of patients and 22.7% had past history of myocardial infarction. Out of 150 patients 117 (78%) underwent thrombus aspiration. No significant difference was found in ST resolution within 60 minutes (72.6 vs 81.8%; P < 0.285) and myocardial blush grade II & III (41.9 vs 27.3%; P < 0.128). No difference in event free survival was observed among the two groups (80.3 vs 84.8%; P < 0.708) at one year. CONCLUSION: Selective thrombus aspiration in definite thrombus laden arteries and no aspiration in low or negligible thrombus burden vessels may be a safe and effective strategy in patients undergoing primary PCI. Overall poor risk profile of our patients as compared to western population necessitates further evaluation of this matter in randomized studies.

Cost effectiveness of routine laparoscopic ultrasound for assessment of resectability of gallbladder cancer.

BACKGROUND: In addition to a diagnostic laparoscopy (DL), a routine laparoscopic ultrasound (LUS) has been proposed to identify undetected hepatic metastases and/or anatomically advanced disease in patients with T2 or higher gall bladder cancer (GBC) patients planned for surgical resection. It was hypothesized that a routine LUS is not a cost-effective strategy for these patients. METHODS: Decision tree modeling was undertaken to compare DL-LUS vs. DL at the time of definitive resection of GBC (with no prior cholecystectomy). Costs in US dollars (payer's perspective), quality-adjusted life weeks (QALWs), and incremental cost-effectiveness ratios (ICER) were calculated (horizon: 6 weeks, willingness-to-pay: $1,000/QALW or $50,000/QALY). RESULTS: DL-LUS was cost effective at the base case scenario (costs: $30,838 for DL vs. $30,791 for DL-LUS and effectiveness 3.81 QALWs DL vs. 3.82 QALW DL-LUS), resulting in a cost reduction of $9,220 per quality-adjusted life week gained (or $479,469 per QALY). DL-LUS became less cost effective as the cost of ultrasound increased or the probability of exclusion from resection decreased. CONCLUSIONS: Routine LUS with DL for the assessment of resectability and exclusion of metastases is cost effective for patients with GBC. Until improvements in preoperative imaging occur to decrease the probability of exclusion, this appears to be a feasible strategy.

Outcome of primary percutaneous coronary intervention at public sector tertiary care hospital in Pakistan.

OBJECTIVES: To determine the outcome of Primary Precutaneous Coronary Intervention (PCI) in our setup and compare the results with the west. METHODS: This study was conducted at a tertiary care teaching Hospital (National Institute of Cardiovascular Diseases Karachi, Pakistan) during January 1st, 2008 to December 31st, 2008. A total of 113 patients were enrolled who came with STEMI and agreed to go for Primary PCI. We excluded the patients who had history of Thrombolytic therapy within 24 hours, presented with Non ST-elevation Myocardial Infarction (NSTEMI) and coronary angiogram revealed significant left Main or equivalent disease. All Patients received Aspirin, Clopidogrel and Platelet Glycoprotein IIB IIIA Inhibitor. After Primary PCI patients were planned to follow at one month, 3 months and 6 months. Primary end point was to document death, MI, CABG and rehospitalization. RESULTS: Out of 113 cases, 102 (90.3%) were male and 11 (9.7%) were female, Mean age was 51.2 +/- 11.7 years, 54 (47.8%) patients had Hypertension, 28 (24.8%) were Diabetics and 44 (38.9%) were Smokers. Immediate success was achieved in 111 (98.2%) cases. In hospital mortality was 5.3% (3.5% in cardiogenic shock, 1.7% in non-shock patients). Mean Door to Balloon time remained 98.4 minutes. Twelve patients were lost to follow up. Therefore at 6 months, out of 101 patients, 8 (7.9%) died, 5 (4.9%) underwent Coronary Artery Bypass Graft (CABG) surgery and 5 (4.9 %) had been re-hospitalized either for recurrent myocardial infarction or heart failure. CONCLUSION: Optimal results of primary percutaneous coronary intervention can be achieved for acute STEMI in a developing country at a tertiary care public sector hospital. The results are comparable and nearly similar to the west.

Comparison of fluoroscopy time during coronary angiography and interventions by radial and femoral routes- can we decrease the fluoroscopy time with increased experience? An observational study.

OBJECTIVE: Radial route of access is increasingly being used for coronary angiograms and intervention. However, radiation exposure of operators was not known in our set up with either transfemoral or transradial procedures. The objective of the study was to compare related peripheral arterial route radiation exposure of operators by assessing fluoroscopy time. The secondary objective was to determine the relationship of operator experience with fluoroscopy time. METHODS: This observational study was conducted in a tertiary care center - Cardiovascular Institute of Karachi (Pakistan) during the period of July 1(st) 2009 to September 30(th) 2009. We studied 1016 consecutive adult patients referred for coronary angiography (CA) or percutaneous coronary intervention (PCI). Patients who underwent right heart catheterization or for valvuloplasty were excluded from the study. Out of these 1016 patients, 928 were diagnostic CAs (734 via femoral route [f-CA] and 194 via radial route [r-CA]) and 88 were PCI (64 via femoral route [f-PCI] and 24 via radial route [r-PCI]). Fluoroscopy time was recorded as a surrogate of radiation exposure. Statistical analysis was performed using unpaired t, Mann-Whitney U, Chi-square and ANOVA tests. RESULTS: Mean fluoroscopy time was found to be significantly higher in patients who underwent r-CA (6.3±3.8 vs 4.0±2.9 min; p<0.001) and r-PCI (15.1±11.8 vs 10.3±7.4 min; p=0.02) as compared with those underwent f-CA and f-PCI. Mean fluoroscopy time of well experienced operators was also high in r-CAs (5.4±2.9 vs 4.2±3.5 min; p=0.004). CONCLUSION: Radial procedures are associated with longer fluoroscopy time that may result in high radiation exposure to radial operators. Even well experienced radial operators cannot minimize their fluoroscopy time to the level of well experienced femoral operators.

Successful transradial percutaneous coronary intervention with radial artery anomaly.

The transradial approach as an access for percutaneous coronary intervention (PCI) has been widely adopted. However, anatomical variations and stenoses may pose significant challenges to the operator. We report a case of successful transradial PCI in a patient with a complete radioulnar loop.