High sensitivity troponin I as a biomarker for cardiac allograft vasculopathy: Evaluation of diagnostic potential and clinical utility.

INTRODUCTION: Cardiac allograft vasculopathy (CAV) limits long-term survival in heart transplant (HTx) recipients. The use of biomarkers in CAV surveillance has been studied, but none are used in clinical practice. The predictive value of high-sensitivity troponin I (hsTnI) has not been extensively investigated in HTx recipients. METHODS: HTx patients undergoing surveillance coronary angiograms and enrolled in the Emory Cardiovascular Biobank had plasma hsTnI measured. CAV grade was assessed using ISHLT nomenclature. Multivariable cumulative link mixed modeling was performed to determine association between hsTnI level and CAV grade. Patients were followed for adverse outcomes over a median 10-year period. Kaplan-Meier survival analysis and Cox proportional hazard modeling were performed. RESULTS: Three hundred and seventy-two angiograms were analyzed in 156 patients at a median 8.9 years after transplant. hsTnI levels were positively correlated with concurrent CAV grade after adjustment for age, age at transplant, sex, BMI, hypertension, diabetes, hyperlipidemia, estimated glomerular filtration rate, and history of acute cellular rejection (p = .016). In an adjusted Cox proportional hazard model, initial hsTnI level above the median (4.9 pg/mL) remained a predictor of re-transplantation or death (hazard ratio 1.82; 95% confidence interval 1.16-2.90; p = .01). CONCLUSION: An elevated hsTnI level reflects severity of CAV and is associated with poor long-term outcomes in patients with HTx.

Association of physical activity with arterial stiffness among Black adults.

Arterial stiffness is a precursor for the development of hypertension and premature cardiovascular disease (CVD). Physical activity has been associated with lower arterial stiffness among largely White populations, but the types of activity required and whether these findings apply to Black adults remain unknown. We examined whether physical activity levels were associated with arterial stiffness among Black adults in two independent cohorts. In the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity, 378 Black adults (age 52.8 ± 10.3, 39.7% male) without known CVD living in Atlanta, GA were recruited. Arterial stiffness was measured as pulse wave velocity (PWV). Total and domain-specific physical activity were assessed by self-report. Multiple linear regression models were used to investigate differences across physical activity levels after adjusting for age, sex, CVD risk factors, and socioeconomic status. Findings were validated in an independent cohort of Black adults (n = 55, age 50.4 ± 9.2, 23.6% male). After adjustment for covariates, lower arterial stiffness was associated with higher self-reported levels of sport/exercise (6.92 ± 1.13 vs 7.75 ± 1.14, p < 0.001, highest vs lowest quartile) and home/life activities (7.34 ± 1.24 vs 7.73 ± 1.07, p = 0.04, highest vs lowest quartile), but not work, active living, or the overall physical activity scores. These findings were replicated in the independent cohort where higher levels of sport/exercise remained associated with lower arterial stiffness (6.66 ± 0.57 vs 8.21 ± 0.66, p < 0.001, highest vs lowest quartile). Higher levels of sport/exercise and home/life-related physical activities (in comparison to occupational physical activity) are associated with lower arterial stiffness in Black adults.

Comprehensive overview of COVID-19 clinical trials.

Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.

Gestational diabetes mellitus in South Asia: Epidemiology.

Gestational diabetes mellitus, is defined by the American Diabetes Association as "diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes". WHO has further classified the period of diagnosis as Hyperglycaemia in Pregnancy and Gestational Diabetes Mellitus. The former term is applicable in the early period of gestation and GDM is detected after 24 weeks. Irrespective of the guidelines followed, the presence of Diabetes Mellitus during pregnancy, has to be taken seriously as it is an important metabolic derangement and can prove to be harmful for the mother and dangerous for the foetus. The rising incidence of Type 2 Diabetes Mellitus in the world along with obesity, is a major contributing factor for GDM. The trend of this rise is more steep in the low and middle income countries thus proportionately increasing the risk for GDM. South Asia falls in this bracket and the responsible factors have to be identified and corrected. Management should begin from primordial prevention for which education is a key factor. Every woman should be taught the way to follow a healthy life style. Identification of the contributing factors and universal screening facilities for all pregnant women living in both rural and urban areas, should be given prime importance. On detecting Hyperglycaemia in Pregnancy or GDM, monitoring and health care facilities should be provided. This review provides some available figures of GDM in South Asia, the risk factors in this population and the steps for prevention.

Impact of delay in admission on the outcome of critically ill patients presenting to the emergency department of a tertiary care hospital from low income country.

OBJECTIVE: To assess the impact of admission delay on the outcome of critical patients. METHODS: The retrospective chart review was done at Aga Khan University Hospital, Karachi, and comprised adult patients visiting the Emergency Department during 2010. Outcome measures assessed were total hospital length of stay, total cost of the visit and in-hospital mortality. Patients admitted within 6 hours of presentation at Emergency Department were defined as non-delayed. Data was analysed using SPSS 19. RESULTS: Of the 49,532 patients reporting at the Emergency Department during the study period, 17,968 (36.3%) were admitted. Of them 2356(13%) were admitted to special or intensive care units, 1595(67.7%) of this sub-group stayed in the Emergency Department for >6 hours before being shifted to intensive care. The study focussed on 325(0.65%) of the total patients; 164(50.5%) in the non-delayed group and 161(49.5%) in the delayed group. The admitting diagnosis of myocardial infarction (p=0.00) and acute coronary syndrome (p=0.01) was significantly more common in the non-delayed group compared to other diagnoses like cerebrovascular attacks (p=0.03) which was significantly more common in the delayed group. There was no significant difference in the hospital length of stay between the two groups (p>0.05). The Emergency Department cost was significantly increased in the delayed group (p<0.05), but there was no difference in the overall hospital cost between the groups (p>0.05). CONCLUSIONS: There was no significant difference in the delayed and non-delayed groups, but long Emergency Department stays are distressing for both physicians and patients.

Trends of acute poisoning: 22 years experience from a tertiary care hospital in Karachi, Pakistan.

OBJECTIVE: To determine the trends of acute poisoning in terms of frequency, nature of poisoning agent, clinical presentation and its outcome. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of patients who presented with poisoning between January 1989 and December 2010.The patients were randomly selected , and demographic, chemical information, clinical feature, treatment and outcome were analysed using SPSS 16. RESULTS: Of the total hospital admissions during the period, 3,189(0.3%) were cases of poisoning. Of them, medical records of 705(22%) cases were reviewed; 462(65.5%) adult and 243(34.5%) paediatric cases below 16 years of age. The overall median age was 21 years (interquartile range: 4-32 years)Moreover, 544(87%) were critical at the time of presentation. In 647(92%) cases, the poisoning occurred at home. Psychiatric drugs were found involved in 205(29%) cases, followed by prescription drugs 172(24.4%), pesticides 108(15.3%), hydrocarbons 71(10%), analgesics 59(8.7%), household toxins 59(8.7%), alcohol and drug abuse 21(2.97%) and others 47(6.67%). CONCLUSIONS: Poisoning was a serious cause of morbidity in children and young adults. Medications were the leading cause and home was the most common place of incident.

Insights on the effects of patient perceptions and awareness on ambulance usage in Karachi, Pakistan.

BACKGROUND: Prehospital care is a vital part of emergency medical care. Countries with decentralised ambulance systems, such as Pakistan, require patient knowledge as to when to call an ambulance and which service to call. Little is known about how patient perceptions of ambulance services affect ambulance usage in most low- and middle-income countries (LMIC). The purpose of our study was to analyse patient perspectives of the ambulance system in Karachi to understand how to improve ambulance use. METHODS: Indepth interviews were conducted with 30 individuals selected by convenience sampling representing patients who came to the emergency department by private transport versus one of two of the main ambulance service providers in Karachi. RESULTS: Similar to what has been shown in some LMIC contexts, two of the major themes that emerged which affect patient decision making with regard to ambulance use were a mistrust of the ambulance system or providers and a sense of inadequacy of the local system as compared with international standards. In addition, which has not been shown in previous studies, there was a fundamental misunderstanding of the role of ambulance services in the healthcare infrastructure. CONCLUSIONS: Insight into the main issues affecting patient decisions to use an ambulance service offers possible targets for patient education that could result in an increase in the proper usage of ambulances and thus optimise outcomes from serious injury and illness in an LMIC context.

Trend over time; a structural review of articles published in Journal of Pakistan Medical Association from 1953-2009.

OBJECTIVE: To review the articles published in the Journal of Pakistan Medical Association from 1953 to 2009 and to assess the components of each article by a pretested proforma containing a checklist of items based on modified 'Strengthening the Reporting of Observational Studies in Epidemiology' statement. METHODS: The retrospective study was conducted at the office of the Journal of Pakistan Medical Association, Karachi, from February to November 2010. A checklist of items in the modified 'Strengthening the Reporting of Observational Studies in Epidemiology' statement was made after discussion among the authors of the study to finally include a revised checklist of 45 items instead of the checklist of 22 items of the statement. A total sample size of 370 was calculated. Simple randomisation was done for selection of articles from each year. For each article, major and minor items were documented. Data was fed into SPSS version 15. RESULTS: The scientific quality of reporting of most of the components of Introduction, Results and Discussion sections have improved progressively with time (p < 0.001) whereas most components of Methodology have remained consistent. CONCLUSION: A change in trend over time was observed over the study period in major and minor items of the articles in the Journal, showing improved reporting of various sub-components of articles.The modified 'Strengthening the Reporting of Observational Studies in Epidemiology' statement provides a checklist that may be used to improve the quality of articles.

Soluble urokinase Plasminogen Activator Receptor (suPAR) mediates the effect of a lower education level on adverse outcomes in patients with coronary artery disease.

AIMS: To investigate whether the adverse impact of lower educational attainment on mortality risk in patients with coronary artery disease (CAD) is mediated by the activation of inflammatory and immune pathways, estimated as elevated soluble urokinase plasminogen activator receptor levels. METHODS AND RESULTS: In 3164 patients undergoing coronary angiography, we investigated multivariable associations between suPAR and educational attainment and assessed the relationship between a lower educational level (defined as a high-school degree or less as the highest educational qualification) and outcomes using Cox proportional hazard and Fine and Gray's subdistribution competing risk models. The potential mediating effect through suPAR and high-sensitivity C-reactive protein (hs-CRP) was assessed using mediation analysis. A total of 1814 patients (57.3%) had achieved a higher (≥college) education level and 1350 patients (42.7%) a lower (≤high school) education level. Soluble urokinase plasminogen activator receptor levels were 9.0% [95% confidence interval (CI) 6.3-11.8, P ≤ 0.0001] higher in patients with lower educational qualifications than in those with higher educational qualifications after covariate adjustment. Lower educational attainment was associated with a higher risk of cardiovascular death after adjustment for demographic, clinical, and behavioural covariates, including CAD severity and heart failure history, medication use, and hs-CRP levels [hazard ratio 1.26 (95% CI 1.02-1.55, P = 0.03)]. However, after adjustment for suPAR levels, the effect of a lower educational level on cardiovascular death became insignificant. Values were similar for all-cause death. Soluble urokinase plasminogen activator receptor levels mediated 49% and hs-CRP levels 17% of the cardiovascular death risk attributable to lower educational attainment. CONCLUSION: Circulating suPAR levels importantly mediate the effects of lower educational attainment on mortality, indicating the importance of systemic inflammation and immune dysregulation as biologic mediators of adverse social determinants of health.

In patients with coronary artery disease (CAD), we demonstrate that nearly half of the higher risk of all-cause and cardiovascular mortality associated with lower educational attainment as a measure of socioeconomic status is mediated by systemic inflammation and immune dysregulation, which can be estimated by measuring the circulating soluble urokinase plasminogen activator receptor (suPAR) levels. Even after accounting for differences in cardiovascular risk factors, lower educational attainment is associated with higher mortality risk in patients with CAD and there is activation of inflammatory pathways and immune dysregulation in those with lower (≤high school) educational attainment than in those with higher (≥college) educational attainment, estimated as higher circulating suPAR levels.Almost half of the higher risk for adverse outcomes observed in those with lower educational attainment appears to be due to systemic inflammation and immune dysregulation and can be estimated from measuring suPAR levels.

Long-Term Outcomes in Patients With Chronic Total Occlusion.

Although a chronic total occlusion (CTO) in the setting of an acute coronary syndrome is associated with greater risk, the prognosis of patients with a CTO and stable coronary artery disease (CAD) remains unknown. This study aimed to investigate adverse event rates in patients with stable CAD with and without a CTO. In 3,597 patients with stable CAD (>50% coronary luminal stenosis) who underwent cardiac catheterization, all-cause mortality, cardiovascular mortality, and the composite major adverse cardiac event (MACE) rates for cardiovascular death, myocardial infarction, and heart failure hospitalization were evaluated. Cox proportional hazards and Fine and Gray subdistribution hazard models were used to compare event-free survival in patient subsets after adjustment for covariates. Event rates were higher in patients with CTOs than in those without CTOs after adjusting for demographic and clinical characteristics (cardiovascular death hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.05 to 1.57, p = 0.012). Patients with CTO revascularization had lower event rates than those of patients without CTO revascularization (cardiovascular death HR 0.43, CI 0.26 to 0.70, p = 0.001). Those with nonrevascularized CTOs were at particularly great risk when compared with those without CTO (cardiovascular death HR 1.52, CI 1.25 to 1.84, p <0.001). Moreover, those with revascularized CTOs had similar event rates to those of patients with CAD without CTOs. Patients with CTO have higher rates of adverse cardiovascular events than those of patients with significant CAD without CTO. This risk is greatest in patients with nonrevascularized CTO.

N terminal pro-brain natriuretic peptide level and benefits of chronic total occlusion revascularization.

BACKGROUND: The management of revascularization of chronic total occlusions (CTOs) remains controversial. Whether specific patients gain survival benefit from CTO revascularization remains unknown. OBJECTIVES: We investigated whether (i) patients with CTO have higher N terminal pro-brain natriuretic peptide (NT pro-BNP) levels than patients without CTO, (ii) in patients with CTO, NT pro-BNP levels predict adverse events, and (iii) those with elevated levels benefit from revascularization. METHODS: In 392 patients with stable, significant coronary artery disease (CAD) and CTO undergoing coronary angiography, rates of all-cause mortality, cardiovascular death, and a composite (cardiovascular death, myocardial infarction and heart failure hospitalizations) were investigated. Unadjusted and adjusted Cox proportional and Fine and Gray sub-distribution hazard models were performed to determine the association between NT pro-BNP levels and incident event rates in patients with CTO. RESULTS: NT pro-BNP levels were higher in patients with, compared to those without CTO (median 230.0 vs. 177.7 pg/mL, p ≤0.001). Every doubling of NT pro-BNP level in patients with CTO was associated with a > 25% higher rate of adverse events. 111 (28.5%) patients underwent CTO revascularization. In patients with elevated NT pro-BNP levels (> 125 pg/mL), those who underwent CTO revascularization had substantially lower adverse event rates compared to patients without CTO revascularization (adjusted cardiovascular death hazard ratio 0.29, 95% confidence interval (0.09-0.88). However, in patients with low NT pro-BNP levels (≤ 125 pg/mL), event rates were similar in those with and without CTO revascularization. CONCLUSION: NT pro-BNP levels can help identify individuals who may benefit from CTO revascularization.

Vitamin D Deficiency, Inflammation, and Diminished Endogenous Regenerative Capacity in Coronary Heart Disease.

Background: Vitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in and may promote greater risk through inflammation and impaired progenitor cell function. Objectives: The authors examined VDD, high-sensitivity C-reactive protein (hsCRP), circulating progenitor cell (CPC) counts, and outcomes in patients with CHD. They hypothesized that the higher risk with VDD is mediated by inflammation and impaired regenerative capacity. Methods: A total of 5,452 individuals with CHD in the Emory Cardiovascular Biobank had measurement of 25-hydroxyvitamin D, subsets of whom had hsCRP measurements and CPCs estimated as CD34-expressing mononuclear cell counts. Findings were validated in an independent cohort. 25-hydroxyvitamin D <20 ng/mL was considered VDD. Cox and Fine-Gray models determined associations between marker levels and: 1) all-cause mortality; 2) cardiovascular mortality; and 3) major adverse cardiovascular events, a composite of adverse CHD outcomes. Results: VDD (43.6% of individuals) was associated with higher adjusted cardiovascular mortality (HR: 1.57, 95% CI: 1.09-2.28). There were significant interactions between VDD and hsCRP and CPC counts in predicting cardiovascular mortality. Individuals with both VDD and elevated hsCRP had the greatest risk (HR: 2.82, 95% CI: 2.16-3.67). Only individuals with both VDD and low CPC counts were at high risk (HR: 2.25, 95% CI: 1.46-3.46). These findings were reproduced in the validation cohort. Conclusions: VDD predicts adverse outcomes in CHD. Those with VDD, inflammation and/or diminished regenerative capacity are at a significantly greater risk of cardiovascular mortality. Whether targeted supplementation in these high-risk groups improves risk warrants further study.

Health care personnel and workplace violence in the emergency departments of a volatile metropolis: results from Karachi, Pakistan.

BACKGROUND: Workplace violence (WPV) is an important challenge faced by health care personnel in the emergency department (ED). STUDY OBJECTIVES: To determine the prevalence and nature of WPV reported by physicians and nurses working in the EDs of four of the largest tertiary care hospitals in Karachi, Pakistan and to understand the mental health impact of experiencing WPV. METHODS: This cross-sectional survey was conducted between September and November 2008 using a widely used questionnaire developed by the World Health Organization. Overall, 266 (86% response rate) questionnaires were included in this study. RESULTS: A total of 44 (16.5%) physicians and nurses said they had been physically attacked, and 193 (72.5%) said that they had experienced verbal abuse in the last 12 months. Among those who reported physical attack, 29.6% reported that the last incident involved a weapon, and in 64% of cases the attacker was a patient's relative. Eighty-six percent thought that the last attack could have been prevented, and 64% said that no action was taken against the attacker. After adjusting for covariates, physicians were less likely than nurses to report physical attack (odds ratio [OR] 0.46; 95% confidence interval [CI] 0.2-1.0), and personnel with greater work experience (OR 4.8; 95% CI 2.0-11.7) and those who said that there were procedures to report WPV in their workplace (OR 3.2; 95% CI 1.6-6.5) were more likely to report verbal abuse. WPV was associated with mental health effects in the form of bothersome memories, super-alertness, and feelings of avoidance and futility. CONCLUSION: WPV is an important challenge in the EDs of large hospitals in Karachi. A majority of respondents feel that WPV is preventable, but only a minority of attackers face consequences.

Reasons behind the increase in research activities among medical students of Karachi, Pakistan, a low-income country.

CONTEXT: Previously, in a low-income country with limited resources like Pakistan, biomedical research was conducted mostly by individuals working in private organizations. Recently, there has been an upsurge in the number of medical students conducting research in both private and public medical colleges of Karachi, Pakistan. We investigated student perceptions of the reasons behind the increase in biomedical research among medical students of private and public medical colleges in Karachi, Pakistan. METHODS: This cross-sectional study was conducted at four medical universities of Karachi, using structured data collection tool. Participants included medical students who stated that they were interested in medical research. We assessed how many had been involved in research or stated that they intended to be, and tallied students' stated reasons why they were involved in research. Chi-square analyses were used to assess if year of training, institution, and other factors were associated with the likelihood of past or current actual research involvement. RESULTS: Out of the 398 students with research interest who participated in the study, 349 (88%) stated that they intended to do research projects in their undergraduate years. At the time of the study, only 202 (51%) reported that they had actually conducted research. The reasons given for engaging in research for a minority included personal interest (n = 136; 34%), while majority stated that their motivation was to improve their curriculum vitae (75%) and/or to be more competitive for a residency in the United States (43%). The reasons students gave for involvement in research were related to whether their schools were public versus private and to their year of study. DISCUSSION: According to students' reports, improving one's curriculum vitae to get a strong residency in the USA appeared to be a principal reason for the increase in biomedical research in Karachi. The challenges of research, such as lack of good mentors and increased work-load were reported to affect few students' ability to engage in research.

Mothers' education and working status; do they contribute to corrosive poisoning among paediatric patients of Karachi, Pakistan?

OBJECTIVE: To determine the causative factors behind corrosive poisoning in children like effect of working mothers, their educational status, financial background, family size and number of siblings. METHODS: The multi-centre, prospective, case series of all paediatric patients presenting to the Emergency Department of the National Institute of Child Health and the Aga Khan University Hospital, Karachi from August 2008 to July 2009 is presented. It comprised all paediatric patients with a history of corrosive poisoning at the two hospitals. SPSS 20 was used for statistical analysis. RESULTS: Out of 105 cases, 56(53%) related to the private-sector Aga Khan University Hospital, and 49(47%) to the public-sector National Institute of Child Health. Of the total, 82(78%) were in 1-5 age group; 61 (58%) were males; and 44(42%) were females. While 59 (56.2%) mothers were educated, only 21 (20%) were working. Of the 46 (43.8%) non-educated mothers, 20 (19%) were working. The type of poison was alkali in 81(77%) cases, acid in 23(22%). The corrosive varied from liquid in 80(76%) cases to powder/gel/semi-solid form in 25(24%) exposures. Besides, 65 (61.9%) families had 3 or more siblings, and the age of siblings was less than 10 in 60 (57.14%) cases, In 34 (32.38%) cases, the chemical were kept in the original container, while in 71 (67.61%) cases other commonly used and familiar containers were used to store these chemicals. Kitchen was the most common place with 51 (48.57%) cases. The time of incident was afternoon in 51(48.57%) cases. Majority cases (n=23; 21.9%) occurred in October. CONCLUSIONS: There are multiple contributory factors in corrosive exposure among children rather than the mother's working status and her educational background.

Intubation in emergency department of a tertiary care hospital in a low-income country.

OBJECTIVE: To study the indications, method, success rate and complications of intubation at the Emergency Department of a private, tertiary care hospital in Karachi, Pakistan. METHODS: The case series involved 278 patients above 14 years of age who underwent emergency intubation at the Emergency Department of Aga Khan University Hospital, Karachi between 1998 and 2003. Descriptive statistics were used to compare rapid sequence intubation with crash intubation. The level of significance was p<0.05. RESULTS: Of the total 278 intubations performed, 37 (13.3%) had to be left out for incomplete information.The study population remaining for inferential analysis comprised of 241 patients. Of the total 278 patients, 174 (63%) were males. Rapid sequence intubation was the commonest type (n=185, 67%) of intubation and was performed mostly by anaesthetists (n=236, 85%). Cardiogenic pulmonary oedema and head injury were commonly seen in these patients.The success on first attempt of intubation was 98% (n=181) in rapid sequence intubation, and 85% (n=48) in crash intubation. Overall, 15 (5.3%) complications were seen in these intubations. CONCLUSION: Study showed a satisfactory success rate in both rapid sequence and crash intubations.

A comparison of WHO guidelines issued in 1997 and 2009 for dengue fever - single centre experience.

OBJECTIVE: To compare the original (1997) and revised (2009) versions of World Health Organization guidelines for dengue patients METHODS: Adult patients with a positive dengue Immunoglobulin M serology, and a diagnosis of dengue were included in the study at Aga Khan University Hospital during a three-year period from January 2005 to December 2007. Data related to these dengue patients was collected from their medical records. Guidelines were then applied by the research assistant and correlation among these guidelines was computed. SPSS 19 was used for statistical analysis. RESULTS: A total of 612 patients were found with a diagnosis of dengue, but only 439 (71.73%) had a positive IgM. The median age of these 439 patients was 28 (interquartile range: 18) years and majority of them were males, 295 (67%). According to the 1997 guidelines, 383 (87%) patients were classified as having dengue, while according to the 2009 guidelines, all the 439 (100%) patients were classified with a dengue infection. Under WHO 1997, 21 (5.5%) cases were classified as dengue shock syndrome, while 2009 guidelines labelled 88 (20%) cases as severe dengue. There was a consensus on only 11 severe cases by both the guidelines, showing different results between the two. CONCLUSION: By using 2009 guidelines, a physician would classify more dengue patients as having severe disease.

High Sensitivity Troponin Level and Benefits of Chronic Total Occlusion Revascularization.

Background The survival benefit of revascularization of chronic total occlusion (CTO) of the coronary arteries remains a subject of controversy. We measured high sensitivity troponin-I (hsTn-I) levels as an estimate of myocardial ischemia in patients with stable coronary artery disease, with the hypothesis that (1) patients with CTO have higher levels of hsTn-I than patients without CTO, (2) hsTn-I levels will predict adverse cardiovascular events in patients with CTO, and (3) patients with elevated hsTn-I levels will have a survival benefit from CTO revascularization. Methods and Results In 428 patients with stable coronary artery disease and CTO undergoing coronary angiography, adverse event rates were investigated. Cox proportional hazards models and Fine and Gray subdistribution hazard models were performed to determine the association between hsTn-I level and incident event rates in patients with CTO. HsTn-I levels were higher in patients with compared with those without CTO (median 6.7 versus 5.6 ng/L, P=0.002). An elevated hsTn-I level was associated with higher adverse event rates (adjusted all-cause mortality hazard ratio, 1.19 [95% CI, 1.08-1.32]; P=0.030) for every doubling of hsTn-I level. CTO revascularization was performed in 28.3% of patients. In patients with a high (>median) hsTn-I level, CTO revascularization was associated with substantially lower all-cause mortality (adjusted hazard ratio, 0.26 [95% CI, 0.08-0.88]; P=0.030) compared with those who did not undergo revascularization. In patients with a low (

Aggregate Clinical and Biomarker-Based Model Predicts Adverse Outcomes in Patients With Coronary Artery Disease.

Despite guideline-based therapy, patients with coronary artery disease (CAD) are at widely variable risk for cardiovascular events. This variability demands a more individualized risk assessment. Herein, we evaluate the prognostic value of 6 biomarkers: high-sensitivity C-reactive protein, heat shock protein-70, fibrin degradation products, soluble urokinase plasminogen activator receptor, high-sensitivity troponin I, and B-type natriuretic peptide. We then develop a multi-biomarker-based cardiovascular event prediction model for patients with stable CAD. In total, 3,115 subjects with stable CAD who underwent cardiac catheterization at Emory (mean age 62.8 years, 17% Black, 35% female, 57% obstructive CAD, 31% diabetes mellitus) were randomized into a training cohort to identify biomarker cutoff values and a validation cohort for prediction assessment. Main outcomes included (1) all-cause death and (2) a composite of cardiovascular death and nonfatal myocardial infarction (MI) within 5 years. Elevation of each biomarker level was associated with higher event rates in the training cohort. A biomarker risk score was created using optimal cutoffs, ranging from 0 to 6 for each biomarker exceeding its cutoff. In the validation cohort, each unit increase in the biomarker risk score was independently associated with all-cause death (hazard ratio 1.62, 95% confidence interval [CI] 1.45 to 1.80) and cardiovascular death/MI (hazard ratio 1.52, 95% CI 1.35 to 1.71). A biomarker risk prediction model for cardiovascular death/MI improved the c-statistic (∆ 6.4%, 95% CI 3.9 to 8.8) and net reclassification index by 31.1% (95% CI 24 to 37), compared with clinical risk factors alone. Integrating multiple biomarkers with clinical variables refines cardiovascular risk assessment in patients with CAD.

Circulating progenitor cells and outcomes in patients with coronary artery disease.

BACKGROUND: Low quantities of circulating progenitor cells (CPCs), specifically CD34+ populations, reflect impairment of intrinsic regenerative capacity. This study investigates the relationship between subsets of CPCs and adverse outcomes. METHODS: 1366 individuals undergoing angiography for evaluation of coronary artery disease (CAD) were enrolled into the Emory Cardiovascular Biobank. Flow cytometry identified CPCs as CD45med blood mononuclear cells expressing the CD34 epitope, with further enumeration of hematopoietic CPCs as CD133+/CXCR4+ cells and endothelial CPCs as vascular endothelial growth factor receptor-2 (VEGFR2+) cells. Adjusted Cox or Fine and Gray's sub-distribution hazard regression models analyzed the relationship between CPCs and 1) all-cause death and 2) a composite of cardiovascular death and non-fatal myocardial infarction (MI). RESULTS: Over a median 3.1-year follow-up period (IQR 1.3-4.9), there were 221 (16.6%) all-cause deaths and 172 (12.9%) cardiovascular deaths/MIs. Hematopoietic CPCs were highly correlated, and the CD34+/CXCR4+ subset was the best independent predictor. Lower counts (≤median) of CD34+/CXCR4+ and CD34+/VEGFR2+ cells independently predicted all-cause mortality (HR 1.46 [95% CI 1.06-2.01], p = 0.02 and 1.59 [95% CI 1.15-2.18], p = 0.004) and cardiovascular death/MI (HR 1.50 [95% CI 1.04-2.17], p = 0.03 and 1.47 [95% CI 1.01-2.03], p = 0.04). A combination of low CD34+/CXCR4+ and CD34+/VEGFR2+ CPCs predicted all-cause death (HR 2.1, 95% CI 1.4-3.0; p = 0.0002) and cardiovascular death/MI (HR 2.0, 95% CI 1.3-3.2; p = 0.002) compared to those with both lineages above the cut-offs. CONCLUSIONS: Lower levels of hematopoietic and endothelial CPCs indicate diminished endogenous regenerative capacity and independently correlate with greater mortality and cardiovascular risk in patients with CAD.