Urinary Calprotectin and Posttransplant Renal Allograft Injury

Objective

Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury.

Methods

In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months.

Results

We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r = −0.33; P<0.001). Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 m² four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66). Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation.

Conclusions

Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation.     

Factors Influencing Graft Outcomes Following Diagnosis of Polyomavirus –Associated Nephropathy after Renal Transplantation

Background

Polyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN.

Methods

Between 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1–4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively.

Results

After 32.1±26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty-eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months (range, 0.25–34.0 months) and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation (OR 20.2, p = 0.042) and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine (OR 16.7, p = 0.055) correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation (HR 46988, p = 0.032) at diagnosis, and high PVAN stage (HR 162.2, p = 0.021) were associated with worse long-term graft survival rates.

Conclusions

The extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN.     

Multivariate Longitudinal Shape Analysis of Human Lateral Ventricles during the First Twenty-Four Months of Life

Background

Little is known about the temporospatial shape characteristics of human lateral ventricles (LVs) during the first two years of life. This study aimed to delineate the morphological growth characteristics of LVs during early infancy using longitudinally acquired MR images in normal healthy infants.

Methods

24 healthy infants were MR imaged starting from 2 weeks old every 3 months during the first and every 6 months during the second year. Bilateral LVs were segmented and longitudinal morphological and shape analysis were conducted using longitudinal mixed effect models.

Results

A significant bilateral ventricular volume increase (p<0.0001) is observed in year one (Left: 126±51% and Right: 145±62%), followed by a significant reduction (p<0.02) during the second year of life (Left: −24±27% and Right: −20±18%) despite the continuing increase of intracranial volume. Morphological analysis reveals that the ventricular growth is spatially non-uniform, and that the most significant growth occurs during the first 6 months. The first 3 months of life exhibit a significant (p<0.01) bilateral lengthening of the anterior lateral ventricle and a significant increase of radius (p<0.01) and area (p<0.01) at the posterior portion of the ventricle. Shape analysis shows that the horns exhibit a faster growth rate than the mid-body. Finally, bilateral significant age effects (p<0.01) are observed for the growth of LVs whereas gender effects are more subtle and significant effects (p<0.01) only present at the left anterior and posterior horns. More importantly, both the age and gender effects are growth directionally dependent.

Conclusions

We have demonstrated the temporospatial shape growth characteristics of human LVs during the first two years of life using a unique longitudinal MR data set. A temporally and spatially non-uniform growth pattern was reported. These normative results could provide invaluable information to discern abnormal growth patterns in patients with neurodevelopmental disorders.     

Early Inflammatory Markers Are Independent Predictors of Cardiac Allograft Vasculopathy in Heart-Transplant Recipients

Background

Identification of risk is essential to prevent cardiac allograft vasculopathy (CAV) and graft failure due to CAV (GFDCAV) in heart transplant patients, which account for 30% of all deaths. Early CAV detection involves invasive, risky, and expensive monitoring approaches. We determined whether prediction of CAV and GFDCAV improves by adding inflammatory markers to a previously validated atherothrombotic (AT) model.

Methods and Findings

AT and inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) were measured in heart biopsies and sera of 172 patients followed prospectively for 8.9±5.0 years. Models were estimated for 5- and 10-year risk using (1) the first post-transplant biopsy only, or (2) all biopsies obtained within 3 months. Multivariate models were adjusted for other covariates and cross-validated by bootstrapping. After adding IL-6 and CRP to the AT models, we evaluated the significance of odds ratios (ORs) associated with the additional inflammatory variables and the degree of improvement in the area under the receiver operating characteristic curve (AUROC). When inflammatory markers were tested alone in prediction models, CRP (not IL-6) was a significant predictor of CAV and GFDCAV at 5 (CAV: p<0.0001; GFDCAV: p = 0.005) and 10 years (CAV: p<0.0001; GFDCAV: p = 0.003). Adding CRP (not IL-6) to the best AT models improved discriminatory power to identify patients destined to develop CAV (using 1^st biopsy: p<0.001 and p = 0.001; using all 3-month biopsies: p<0.04 and p = 0.008 at 5- and 10-years, respectively) and GFDCAV (using 1^st biopsy: 0.92 vs. 0.95 and 0.86 vs. 0.89; using all 3-month biopsies: 0.94 vs. 0.96 and 0.88 vs. 0.89 at 5- and 10-years, respectively), as indicated by an increase in AUROC.

Conclusions

Early inflammatory status, measured by a patient''s CRP level (a non-invasive, safe and inexpensive test), independently predicts CAV and GFDCAV. Adding CRP to a previously established AT model improves its predictive power.     

Gestation Dependant Changes in Angiogenic Factors and Their Associations with Fetal Growth Measures in Normotensive Pregnancy

Background

Earlier studies indicate that altered angiogenesis at birth is associated with poor birth outcome in women with preeclampsia. Now, we hypothesize that the progressive gestation dependant changes in markers of angiogenesis will be more useful to predict birth weight early even in a normotensive pregnancy. This study for the first time examines the association of gestation dependant changes in the levels of maternal angiogenic factors in addition to their levels in cord with birth weight.

Method

Ninety two pregnant women were followed at three different time points: 16–20 weeks, 26–30 weeks and at delivery during pregnancy. Plasma levels of angiogenic and anti angiogenic factors were determined by commercial enzyme-linked immunosorbent assay (ELISA) kits.

Results

Maternal plasma VEGF levels increased (p<0.01) till the second time point and decreased (p<0.05) up to delivery while plasma sFlt-1 levels increased (p<0.01) at delivery. PlGF levels peaked (p<0.01) at second time point and decreased (p<0.01) at delivery. Cord plasma VEGF levels were higher (p<0.01) and sFlt-1 levels were lower (p<0.01) as compared to maternal values at all time points. Maternal plasma VEGF levels at first time point and PlGF levels at delivery were positively (p<0.05 and p<0.01 respectively), while sFlt-1/PlGF ratio at delivery was negatively associated (p<0.05) with birth weight.

Conclusion

Levels of pro- and anti-angiogenic factors may be differentially regulated across gestation. Maternal VEGF levels at early gestation (16–20 weeks) may be predictive of birth weight in healthy term pregnancies.     

Robotic versus Open Partial Nephrectomy: A Systematic Review and Meta-Analysis

Objectives

To critically review the currently available evidence of studies comparing robotic partial nephrectomy (RPN) and open partial nephrectomy (OPN).

Materials and Methods

A comprehensive review of the literature from Pubmed, Web of Science and Scopus was performed in October 2013. All relevant studies comparing RPN with OPN were included for further screening. A cumulative meta-analysis of all comparative studies was performed and publication bias was assessed by a funnel plot.

Results

Eight studies were included for the analysis, including a total of 3418 patients (757 patients in the robotic group and 2661 patients in the open group). Although RPN procedures had a longer operative time (weighted mean difference [WMD]: 40.89; 95% confidence interval [CI], 14.39–67.40; p = 0.002), patients in this group benefited from a lower perioperative complication rate (19.3% for RPN and 29.5% for OPN; odds ratio [OR]: 0.53; 95%CI, 0.42–0.67; p<0.00001), shorter hospital stay (WMD: −2.78; 95%CI, −3.36 to −1.92; p<0.00001), less estimated blood loss(WMD: −106.83; 95%CI, −176.4 to −37.27; p = 0.003). Transfusions, conversion to radical nephrectomy, ischemia time and estimated GFR change, margin status, and overall cost were comparable between the two techniques. The main limitation of the present meta-analysis is the non-randomization of all included studies.

Conclusions

RPN appears to be an efficient alternative to OPN with the advantages of a lower rate of perioperative complications, shorter length of hospital stay and less blood loss. Nevertheless, high quality prospective randomized studies with longer follow-up period are needed to confirm these findings.     

Osteoprotegerin,Pericytes and Bone-Like Vascular Calcification Are Associated with Carotid Plaque Stability

Background and Purpose

Vascular calcification, recapitulating bone formation, has a profound impact on plaque stability. The aim of the present study was to determine the influence of bone-like vascular calcification (named osteoid metaplasia = OM) and of osteoprotegerin on plaque stability.

Methods

Tissue from carotid endarterectomies were analysed for the presence of calcification and signs of vulnerability according to AHA grading system. Osteoprotegerin (OPG), pericytes and endothelial cells were sought using immuno-histochemistry. Symptoms and preoperative imaging findings (CT-scan, MRI and Doppler-scan) were analyzed. Human pericytes were cultured to evaluate their ability to secrete OPG and to influence mineralization in the plaque.

Results

Seventy-three carotid plaques (49 asymptomatic and 24 symptomatic) were harvested. A significantly higher presence of OM (18.4% vs 0%, p<0.01), OPG (10.2% of ROI vs 3.4% of ROI, p<0.05) and pericytes (19% of ROI vs 3.8% of ROI, p<0.05) were noted in asymptomatic compared to symptomatic plaques. Consistently, circulating OPG levels were higher in the plasma of asymptomatic patients (3.2 ng/mL vs 2.5 ng/mL, p = 0.05). In vitro, human vascular pericytes secreted considerable amounts of OPG and underwent osteoblastic differentiation. Pericytes also inhibited the osteoclastic differentiation of CD14+ cells through their secretion of OPG.

Conclusions

OPG (intraplaque an plasmatic) and OM are associated with carotid plaque stability. Pericytes may be involved in the secretion of intraplaque OPG and in the formation of OM.     

Complaints of Poor Sleep and Risk of Traffic Accidents: A Population-Based Case-Control Study

Introduction

This study aimed to determine the sleepiness-related factors associated with road traffic accidents.

Methods

A population based case-control study was conducted in 2 French agglomerations. 272 road accident cases hospitalized in emergency units and 272 control drivers matched by time of day and randomly stopped by police forces were included in the study. Odds ratios were calculated for the risk of road traffic accidents.

Results

As expected, the main predictive factor for road traffic accidents was having a sleep episode at the wheel just before the accident (OR 9.97, CI 95%: 1.57–63.50, p<0.05). The increased risk of traffic accidents was 3.35 times higher in subjects who reported very poor quality sleep during the last 3 months (CI 95%: 1.30–8.63, p<0.05), 1.69 times higher in subjects reporting sleeping 6 hours or fewer per night during the last 3 months (CI 95%: 1.00–2.85, p<0.05), 2.02 times higher in subjects reporting symptoms of anxiety or nervousness in the previous day (CI 95%: 1.03–3.97, p<0.05), and 3.29 times higher in subjects reporting taking more than 2 medications in the last 24 h (CI 95%: 1.14–9.44, p<0.05). Chronic daytime sleepiness measured by the Epworth Sleepiness Scale, expressed heavy snoring and nocturnal leg movements did not explain traffic accidents.

Conclusion

Physicians should be attentive to complaints of poor sleep quality and quantity, symptoms of anxiety-nervousness and/or drug consumption in regular car drivers.     

Association of Severe Thrombocytopenia and Poor Prognosis in Pregnancies with Aplastic Anemia

Purpose

We sought to estimate the risks of adverse obstetric outcomes and disease outcomes associated with severe thrombocytopenia in pregnant women with aplastic anemia (AA).

Methods

In a retrospective study, we compared demographics, clinical characteristics, laboratory results, and outcomes between severe thrombocytopenia (ST) and non-severe thrombocytopenia (non-ST) groups comprising pregnant women with AA.

Results

Of 61 AA patients, 43 (70%) were diagnosed as AA before pregnancy and 18 (30%) were AA during pregnancy. The ST group exhibited lower gestational age at nadir of platelet count (26.0 versus 37.0 weeks, p<0.001) and at delivery (37.3 versus 39.1 weeks, p = 0.008), and a higher rate of bleeding gums (33.8 versus 7.7%, p = 0.015) than the non-ST group. In addition, the ST group exhibited more transfusions during pregnancy (72.7 versus 15.4%, p<0.001) and postpartum period (45.0 versus 2.7%, p<0.001), and more bone marrow transplant after delivery (25.0 versus 0.0%, p<0.001) than the non-ST group. The ST group had a higher odds ratio of composite disease complications (OR, 9.63; 95% CI, 2.82–32.9; p<0.001) and composite obstetric complications (OR, 6.78; 95% CI, 2.11–21.8; p = 0.001) than the non-ST group.

Conclusions

Severe thrombocytopenia is more associated with obstetric and disease complications than is non-severe thrombocytopenia in pregnant women with AA.     

A New Synthetic FGF Receptor Antagonist Inhibits Arteriosclerosis in a Mouse Vein Graft Model and Atherosclerosis in Apolipoprotein?E-Deficient Mice

Objective

The role of fibroblast growth factors (FGFs) in the development of vascular diseases remains incompletely understood. The objective of this study was to examine the effects of a new small-molecule multi-FGF receptor blocker with allosteric properties, SSR128129E, on neointimal proliferation after a vein graft procedure in mice and on the development of atherosclerosis in atherosclerosis-prone apolipoprotein E (apoE)-deficient mice.

Methods and Results

Vein grafts were performed in 3 month-old male C57BL6 mice. Segments of the vena cava were interposed at the level of the carotid artery. In SSR128129E (50 mg/kg/d)-treated animals, a dramatic decrease in neointimal proliferation was observed 2 and 8 weeks after the graft (72.5 %, p<0.01, and 47.8 %, p<0.05, respectively). Four-week old male apoE-deficient mice were treated with SSR128129E (50 mg/kg/d) for 3 and 5 months in comparison with a control group. SSR128129E treatment resulted in a reduction of lesion size in the aortic sinus (16.4 % (ns) at 3 months and 42.9 % (p<0.01) at 5 months, without any change in serum lipids. SSR128129 significantly reduced FGFR2 mRNA levels in the aortic sinus (p<0.05, n=5-6), but did not affect the mRNA expression levels of other FGF receptors or ligands.

Conclusion

These studies indicate that FGFs have an important role in the development of vascular diseases like atherosclerosis and graft arteriosclerosis. These data suggest that inhibition of FGF receptors by compounds like SSR128129E might be useful as a new therapeutic approach for these vascular pathologies.     

Serum fetuin A and chemerin levels correlate with hepatic steatosis and regional adiposity in maintenance hemodialysis patients

Background

A deficiency of fetuin A is linked to cardiovascular calcification and mortality in dialysis patients. But, high levels of fetuin A and chemerin correlate with hepatic steatosis and regional adiposity in general population. The association between hepatic steatosis and fetuin A/chemerin levels in hemodialysis (HD) remains unclear.

Methods

We performed a cross-sectional, observational study; 216 prevalent HD patients from a single center were enrolled. Baseline serum fetuin A, chemerin levels, conicity index and anthropometric parameters were checked. Presence of hepatic steatosis was qualified by liver ultrasound and quantified by the hepato-renal index (HRI); central obesity defined by waist circumference (WC). ROC analyses and multivariate logistic regression analyses for prediction of hepatic steatosis and central obesity on the basis of fetuin A/chemerin levels, anthropometric parameters, and other relevant covariates were performed.

Results

Data from 103 women and 113 men (mean age 60±12 years) were analyzed. Eighty subjects had hepatic steatosis and their HRIs were significantly higher than those without hepatic steatosis (P<0.001). Serum fetuin A levels were positively associated with HRIs (P<0.001) and chemerin levels (P<0.001). Fetuin A, chemerin and WC were predictors for hepatic steatosis and central obesity by ROC curve. In multivariate logistic regression analysis, fetuin A and WC independently predicted hepatic steatosis defined by HRIs. And chemerin predicted central obesity and regional adiposity after covariate adjustments (all P<0.05).

Conclusions

Serum fetuin A levels were higher in prevalent HD patients with hepatic steatosis, and positively correlated with chemerin levels. Chemerin levels predicted central obesity as well as regional adiposity in the HD patients.     

Effects of Growth Hormone (GH) Therapy Withdrawal on Glucose Metabolism in Not Confirmed GH Deficient Adolescents at Final Height

Context, objective

Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR).

Design, setting

We performed a longitudinal study (1 year) in a tertiary care center.

Methods

23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%β, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR.

Results

In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMAβ and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMAβ, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01).

Conclusions

In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-β and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view.     

The Association between Aortic Calcification and Fracture Risk in Postmenopausal Women in China: The Prospective Chongqing Osteoporosis Study

Purpose

Fractures are associated with cardiovascular diseases in the elderly. The purpose of the present study was to investigate the association between aortic calcification (AC) and the risk of vertebral fractures in postmenopausal Chinese women.

Methods

A prospective study with 5 years of follow-up in 1724 postmenopausal women (aged 50 years old and older) was conducted from July 2005 to June 2010. Dual energy X-ray absorptiometry was utilized to evaluate bone mineral density (BMD). Aortic calcification score (ACS) was determined by a semi-quantitative method and was further categorized into four groups. Cox proportional hazards models were established to assess the association between AC and the risk of vertebral fractures.

Results

For subjects with AC, the incidence of vertebral fractures was higher than that of those without AC (p<0.01). After adjustment for age and other potential confounders, it was found that severe AC (G4, ACS>6; G3, ACS = 3–6) was associated with vertebral fractures. Severe AC (G4) was associated with non-vertebral fractures. There were higher risk for the vertebral fractures in two groups and higher risk for non-vertebral fractures in one group.

Conclusions

The results of the current study indicate that severe AC is associated with a significantly increased risk of vertebral fractures and non-vertebral fractures in postmenopausal women in China.     

Synaptic Plasticity in the Hippocampus of a APP/PS1 Mouse Model of Alzheimer's Disease Is Impaired in Old but Not Young Mice

Background

Alzheimer disease (AD) is a neurodegenerative disorder for which there is no cure. We have investigated synaptic plasticity in area CA1 in a novel AD mouse model (APPPS1-21) which expresses the Swedish mutation of APP and the L166P mutation of human PS-1. This model shows initial plaque formation at 2 months in the neocortex and 4 months in the hippocampus and displays β−amyloid-associated pathologies and learning impairments.

Methodology/Principal Findings

We tested long-term potentiation (LTP) and short term potentiation (paired-pulse facilitation, PPF) of synaptic transmission in vivo in area CA1 of the hippocampus. There was no difference in LTP or PPF at 4–5 months of age in APPPS1-21 mice compared to littermate controls. At 6 months of age there was also no difference in LTP but APPPS1-21 mice showed slightly increased PPF (p<0.03). In 8 months old mice, LTP was greatly impaired in APPPS-21 animals (p<0.0001) while PPF was not changed. At 15 months of age, APPPS1-21 mice showed again impaired LTP compared to littermate controls (p<0.005), and PPF was also significantly reduced at 80 ms (p<0.005) and 160 ms (p<0.01) interstimulus interval. Immunohistological analysis showed only modest amyloid deposition in the hippocampus at 4 and 6 months with a robust increase up to 15 months of age.

Conclusions

Our results suggest that increased formation and aggregation of beta amyloid with aging is responsible for the impaired LTP with aging in this mouse model, while the transient increase of PPF at 6 months of age is caused by some other mechanism.     

Effects of Moderate Aerobic Exercise Training on Hemorheological and Laboratory Parameters in Ischemic Heart Disease Patients

Background and Design

In this study we set out to determine the effects of long-term physical training on hemorheological, laboratory parameters, exercise tolerability, psychological factors in cardiac patients participating in an ambulatory rehabilitation program.

Methods

Before physical training, patients were examined by echocardiography, tested on treadmill by the Bruce protocol, and blood was drawn for laboratory tests. The enrolled 79 ischemic heart disease patients joined a 24-week cardiac rehabilitation training program. Blood was drawn to measure hematocrit (Hct), plasma and whole blood viscosity (PV, WBV), red blood cell (RBC) aggregation and deformability. Hemorheological, clinical chemistry and psychological measurements were repeated 12 and 24 weeks later, and a treadmill test was performed at the end of the program.

Results

After 12 weeks Hct, PV, WBV and RBC aggregation were significantly decreased, RBC deformability exhibited a significant increase (p<0.05). Laboratory parameters (triglyceride, uric acid, hsCRP and fibrinogen) were significantly decreased (p<0.05). After 24 weeks the significant results were still observed. By the end of the study, IL-6 and TNF-α levels displayed decreasing trends (p<0.06). There was a significant improvement in MET (p<0.001), and the BMI decrease was also significant (p<0.05). The vital exhaustion parameters measured on the fatigue impact scale indicated a significant improvement in two areas of the daily activities (p<0.05).

Conclusions

Regular physical training improved the exercise tolerability of patients with ischemic heart disease. Previous publications have demonstrated that decreases in Hct and PV may reduce cardiovascular risk, while a decrease in RBC aggregation and an increase in deformability improve the capillary flow. Positive changes in laboratory parameters and body weight may indicate better oxidative and inflammatory circumstances and an improved metabolic state. The psychological findings point to an improvement in the quality of life.     

The Post-Resuscitative Urinalysis Associate the Survival of Patients with Non-Traumatic Out-of-Hospital Cardiac Arrest

Objective

To analyze whether urine output and urinalysis results are predictive of survival and neurologic outcomes in patients with non-traumatic out-of-hospital cardiac arrest (OHCA).

Methods

Information was obtained from 1,340 patients with non-traumatic OHCA who had achieved a sustained return of spontaneous circulation (ROSC). Factors that were associated with survival in the post-resuscitative period were evaluated. The association between urine output and fluid challenge in the early resuscitative period was analyzed and compared between the survivors and the non-survivors. The results of the initial urinalysis, including the presence of proteinuria and other findings, were used to evaluate the severity of vascular protein leakage and survival. The association between proteinuria and the neurologic outcomes of the survivors was also analyzed. The clinical features of capillary leakage were examined during the post-resuscitative period.

Results

Of the 1,340 patients, 312 survived. A greater urine output was associated with a higher chance of survival. The initial urine output increased in proportion to the amount of fluid that was administered during early resuscitation in the emergency department for the survivors but not for the non-survivors (p<0.05). In the initial urinalysis, proteinuria was strongly associated with survival, and severe proteinuria indicated significantly poorer neurologic outcomes (p<0.05 for both comparisons). Proteinuria was associated with a risk of developing signs of capillary leakage, including body mass index gain and pitting edema (both p<0.001).

Conclusion

The severity of proteinuria during the early post-resuscitative period was predictive of survival.     

Antenatal Screening for Down Syndrome Using Serum Placental Growth Factor with the Combined,Quadruple, Serum Integrated and Integrated Tests

Objective

To estimate the value of first or second trimester placental growth factor (PlGF) as an additional antenatal screening marker for Down syndrome.

Design

Nested case-control study.

Setting

Antenatal screening service.

Population or Sample

532 Down syndrome pregnancies and 1,155 matched unaffected pregnancies.

Methods

Stored maternal serum samples (−40°C) were assayed for PlGF. Monte Carlo simulation was used to estimate the screening performance of PlGF with the Combined, Quadruple, serum Integrated and Integrated tests.

Main Outcome Measures

Median PlGF levels in affected and unaffected pregnancies and screening performance (detection rates [DR] for specified false-positive rates [FPR] and vice versa).

Results

First trimester median PlGF was 15%, 28% and 39% lower in Down syndrome than unaffected pregnancies at 11, 12 and 13 completed weeks’ gestation respectively (all p<0.001). Second trimester median PlGF was 31% lower at 14 weeks (p<0.001), and the difference decreased (6% lower at 17 weeks). At a 90% DR with first trimester markers measured at 13 weeks, adding PlGF decreased the FPR from 11.1 to 5.1% using the Combined test, 9.3% to 4.5% using the serum Integrated test, and 3.4% to 1.5% using the Integrated test (or 1.5 to 1.4% with first trimester markers measured at 11 weeks). Adding PlGF to the Quadruple test (measured at 15 weeks) decreased the FPR from 10.0% to 9.6% at a 90% DR.

Conclusions

First trimester PlGF measurements improve the performance of antenatal screening for Down syndrome using the Combined, serum Integrated and Integrated tests. Second trimester PlGF measurements are of limited value.     

Cardiovascular Changes in Atherosclerotic ApoE-Deficient Mice Exposed to Co60 (γ) Radiation

Background

There is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation.

Methods and Results

B6.129P2-ApoE tmlUnc mice on a low-fat diet were acutely exposed (whole body) to Co60 (γ) (single dose 0, 0.5, and 2 Gy) at a dose rate of 36.32 cGy/min, or repeatedly (cumulative dose 0 and 2 Gy) at a dose-rate of 0.1 cGy/min for 5 d/wk, over a period of 4 weeks. Biological endpoints were investigated after 3–6 months of recovery post-radiation. The nitrative stress marker 3-nitrotyrosine and the vasoregulator peptides endothelin-1 and endothelin-3 in plasma were increased (p<0.05) in a dose-dependent manner 3–6 months after acute or chronic exposure to radiation. The oxidative stress marker 8-isoprostane was not affected by radiation, while plasma 8-hydroxydeoxyguanosine and L-3,4-dihydroxyphenylalanine decreased (p<0.05) after treatment. At 2Gy radiation dose, serum cholesterol was increased (p = 0.008) relative to controls. Percent lesion area increased (p = 0.005) with age of animal, but not with radiation treatment.

Conclusions

Our observations are consistent with persistent nitrative stress and activation of the endothelinergic system in ApoE−/− mice after low-level ionizing radiation exposures. These mechanisms are known factors in the progression of atherosclerosis and other cardiovascular diseases.     

Potential Role of M. tuberculosis Specific IFN-γ and IL-2 ELISPOT Assays in Discriminating Children with Active or Latent Tuberculosis

Background

Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI).

Objective

Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB.

Methods

Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens.

Results

Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs.

Conclusion

Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB.     

Overestimation of Vitamin A Supplementation Coverage from District Tally Sheets Demonstrates Importance of Population-Based Surveys for Program Improvement: Lessons from Tanzania

Background

Tanzania has conducted a national twice-yearly Vitamin A supplementation (VAS) campaign since 2001. Administrative coverage rates based on tally sheets consistently report >90% coverage; however the accuracy of these rates are uncertain due to potential errors in tally sheets and their aggregation, incomplete or inaccurate reporting from distribution sites, and underestimating the target population.

Objectives

The post event coverage survey in Mainland Tanzania sought to validate tally-sheet based national coverage estimates of VAS and deworming for the June 2010 mass distribution round, and to characterize children missed by the national campaign.

Methods

WHO/EPI randomized cross-sectional cluster sampling methodology was adapted for this study, using 30 clusters by 40 individuals (n = 1200), in addition to key informant interviews. Households with children 6–59 months of age were included in the study (12–59 months for deworming analysis). Chi-squared tests and logistic regression analysis were used to test differences between children reached and not reached by VAS. Data was collected within six weeks of the June 2010 round.

Results

A total of 1203 children, 58 health workers, 30 village leaders and 45 community health workers were sampled. Preschool VAS coverage was 65% (95% CI: 62.7–68.1), approximately 30% lower than tally-sheet coverage estimates. Factors associated with not receiving VAS were urban residence [OR = 3.31; p = 0.01], caretakers who did not hear about the campaign [OR = 48.7; p<0.001], and Muslim households [OR<3.25; p<0.01]. There were no significant differences in VAS coverage by child sex or age, or maternal age or education.

Conclusion

Coverage estimation for vitamin A supplementation programs is one of most powerful indicators of program success. National VAS coverage based on a tally-sheet system overestimated VAS coverage by ∼30%. There is a need for representative population-based coverage surveys to complement and validate tally-sheet estimates.