Date Of Blood Sampling Research Articles

Renal impairment and abnormal liver function tests in pre-therapeutic phenotype-based DPD deficiency screening using uracilemia: a comprehensive population-based study in 1138 patients.

Dihydropyrimidine dehydrogenase (DPD) deficiency screening is a pre-therapeutic standard to prevent severe fluoropyrimidine-related toxicity. Although several screening methods exist, the accuracy of their results remains debatable. In France, the uracilemia measurement is considered the standard in DPD deficiency screening. The objective of this study was to describe the hyperuracilemia (⩾16 ng/mL) rate and investigate the influence of hepatic and renal impairment in uracilemia measurements since the guidelines were implemented. Using a cohort of 1138 patients screened between 18 October 2018 and 18 October 2021, basic demographic characteristics, date of blood sampling, and potential biological confounders including liver function tests [aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and bilirubin] and estimated glomerular filtration rate (eGFR) were collected. The second same-patient uracilemia analysis was also performed. Temporal change was graphically represented while potential confounders were stratified to show linearity when suspected. Hyperuracilemia was diagnosed in 12.7% (n = 150) samples with 6.7%, 5.4%, 0.5%, and 0.08% between 16 and 20 ng/mL, 20 and 50 ng/mL, 50 and 150 ng/mL, and >150 ng/mL, respectively. The median uracilemia concentration was 9.4 ng/mL (range: 1.2 and 172.3 ng/mL) and the monthly hyperuracilemia rate decreased steadily from >30% to around 9%. Older age, normalized AST, γGT, ALP results, bilirubin levels, and decreased eGFR were linearly associated with higher plasma uracil concentrations (all p < 0.001). In the adjusted multivariate linear model, AST, eGFR, and ALP remained associated with uracilemia (p < 0.05). When measured twice in 39 patients, the median uracilemia rate of change was -2.5%, which subsequently changed the diagnosis in nine patients (23.1%). Better respect of pre-analytical conditions may explain the steady decrease in monthly hyperuracilemia rates over the 3 years. Elevated AST, ALP levels, and reduced eGFR could induce a false increase in uracilemia and second uracilemia measurements modified the first DPD deficiency diagnosis in almost 25% of the patients.

Humoral response to vaccination against SARS-CoV-2 in patients undergoing dialysis

Patients undergoing maintenance dialysis have a higher mortality rate associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and response rates to vaccination against SARS-CoV-2 vary from 29.6% to 96.4% in such patients. This study aimed to assess the immunogenicity of SARS-CoV-2 vaccination in Korean patients undergoing dialysis. We enrolled 70 SARS-CoV-2-vaccinated patients undergoing dialysis, with 11 healthcare workers serving as healthy control subjects. Thirty-two patients had received a third vaccination, whereas 38 had received 2 vaccinations. The healthy control subjects completed the second vaccination. Immunoglobulin G (IgG) antibodies targeting the receptor-binding domain of the S1 subunit of the SARS-CoV-2 spike protein were measured The vaccination responder rates were 86% (37/43), 96% (26/27), and 91% (10/11) in the patients undergoing hemodialysis and peritoneal dialysis and healthy controls, respectively. IgG antibody levels were significantly higher when a third dose was administered, independent of the type of vaccine or the time interval between vaccination and the subsequent blood sampling date. When a third dose of vaccine was administered, there was no difference in IgG antibody levels between those receiving cross-vaccination or a single vaccine. There was no significant difference in IgG antibodies between healthy controls and patients undergoing dialysis. Patients on dialysis exhibited a sufficient antibody-related response to vaccination against SARS-CoV-2, even in those receiving cross-vaccination, and the antibody titer was higher after a third vaccination. Therefore, it is necessary to administer a third vaccine dose to Korean patients undergoing dialysis.

Seasonal Changes in Vitamin D Levels of Healthy Children in Mid-Latitude, Asian Urban Area.

PurposeThis study aimed to investigate the seasonal changes in vitamin D levels in a healthy pediatric population living in mid-latitude East Asian urban areas.MethodsA pediatric population was selected from single secondary hospital visitors. Clinical data and serum vitamin D levels were collected retrospectively. Statistical analyses were performed based on the month of the blood sampling date, subject age, and vitamin D supplementation history. The data were categorized into three subgroups based on serum vitamin D levels—adequate (≥30 ng/mL), insufficient (20–29 ng/mL), and deficient (<20 ng/mL).ResultsOf the 481 patients, 172 had vitamin D supplementation history. More than 70% of the total study population had inadequate vitamin D levels (<30 ng/mL). The non-supplemented group and the supplemented group showed significantly uneven monthly distribution of the adequate, insufficient, and deficient subgroups. Only the non-supplemented group showed significantly different average vitamin D levels in the summer months compared to the winter months. In the non-supplemented group, vitamin D levels were the lowest in March, the highest in August and September. Significant relevance was noted between vitamin D supplementation status and vitamin D serum level in February and March. There was no significant difference between different age groups in terms of the distribution of vitamin D levels.ConclusionCurrently-widespread vitamin D replacement methods seem to have some effect on increasing the overall serum vitamin D levels, specifically during late winter when natural serum vitamin D levels plunge. However, they are unable to fully compensate the seasonal fluctuation.

Soluble ST2 protein as a new biomarker in patientswith precapillary pulmonary hypertension

IntroductionNon-invasive tests that may improve clinical evaluation of pulmonary hypertension (PH) are needed. The purpose of this study was to assess the role of soluble ST2 (sST2) in patients with PH.Material and methodsA total of 57 patients with chronic thromboembolic PH and 43 patients with idiopathic arterial PH were enrolled in this study. All patients were evaluated for World Health Organization (WHO) functional class (FC), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), troponin T (TnT), and hemodynamics. Plasma sST2 was assessed by an immu­nofluorescent in vitro diagnostic assay. All patients were followed up from the date of blood sampling. The endpoint was all-cause death.ResultsThe median sST2 concentration was 32.8 ng/ml (IQR: 21.6–48.5 ng/ml) in the whole study population. Significant differences were found between median sST2 in successive WHO FCs (FC II vs. FC III, p = 0.002; FC III vs. FC IV, p = 0.12; FC II vs. FC IV, p = 0.008). Significant correlations were found between sST2 and hemodynamic parameters: mean right atrial pressure (r = 0.56; p &lt; 0.05), mean pulmonary artery pressure (r = 0.25; p &lt; 0.05), cardiac index (r = –0.40; p &lt; 0.05), pulmonary vascular resistance (r = 0.41; p &lt; 0.05), and between sST2 and WHO FC (r = 0.36; p &lt; 0.05), NT-proBNP (r = 0.55; p &lt; 0.05), and TnT (r = 0.44; p &lt; 0.05). sST2 concentration above the median was associated with worse clinical prognosis (p = 0.02, Kaplan-Meier).ConclusionssST2 seems to be a marker of poor clinical prognosis in patients with PH.

Seasonal periodicity of serum parathyroid hormone and its relation with vitamin D in Romania.

Seasonal variation of parathyroid hormone (PTH) and its dependency on serum 25-hydroxy vitamin D (25(OH)D) levels are well-described. However, there are few studies from Europe, and genetic, nutritional, and cultural differences are important. We describe the seasonal variation of serum PTH and its relation with serum 25(OH)D levels in Romania. We retrieved from our endocrinology center database all PTH measurements between 2011 and 2019 together with age, sex, diagnosis, and date of blood sampling. Simultaneous serum 25(OH)D levels were partially available. Intact PTH was measured using the same electrochemiluminescence assay. There were 8409 subjects (median age 49 (36, 60) years; 20.5% men) without a diagnosis of hyperparathyroidism (primary or secondary to chronic kidney disease), hypoparathyroidism, or low bone mass. Serum PTH showed a mild seasonal variation with highest levels at the end of March (47.61pg/mL) and lowest levels at the end of September (43.15pg/mL). All sex and age subgroups showed highest levels in the spring and lowest levels in the fall. Males had significantly lower PTH levels than females irrespective of season. PTH correlated inversely with serum 25(OH)D with a breakpoint of 12.82ng/mL in 2800 subjects who had a simultaneous measurement of 25(OH)D. Increasing age was associated with increasing PTH levels independently of serum 25(OH)D. We showed a mild seasonal variation of serum PTH in Romania, at an inverse sinusoidal pattern than serum 25(OH)D. The breakpoint on the PTH-25(OH)D correlation suggests that vitamin D supplementation is warranted only in at-risk groups.

Serum human epididymis protein 4 level as a predictor of clinical worsening in idiopathic pulmonary arterial hypertension: a pilot study

BackgroundHuman epididymis protein 4 (HE4) was proved to be a novel biomarker for left heart failure. The purpose of this exploratory study was to evaluate the role of HE4 in patients with idiopathic pulmonary arterial hypertension (IPAH) who usually have concurrent right heart failure.Methods55 patients with newly diagnosed IPAH were continuously enrolled and serum HE4 levels were assessed at baseline. All patients were followed up from the date of blood sampling, and a composite endpoint of clinical worsening was detailedly recorded.ResultsSerum levels of HE4 were significantly higher in IPAH patients than healthy controls (6.9 ± 2.2 vs 4.4 ± 0.9 ng/ml, p < 0.05) and increased as cardiac function deteriorated. HE4 levels correlated with endothelin-1 (r = 0.331, p < 0.01) and right atrial pressure (r = 0.30, p < 0.03). After a mean follow-up of 20 ± 10 months, 13 patients experienced clinical worsening. Receiver operating characteristic analysis showed that HE4 levels > 6.5 ng/ml discriminated clinical worsening with a sensitivity of 92.31% and a specificity of 59.52% (area under the curve [AUC] = 0.81). Multivariate Cox regression analysis demonstrated that HE4 (χ2: 5.10; hazard ratio [HR] = 1.26; 95% confidence interval: 1.03 to 1.55, p < 0.02) and pulmonary vascular resistance (χ 2: 4.19; HR = 1.14; 95% confidence interval: 1.00–1.29, p < 0.04) were independently predictive of clinical worsening. Patients with HE4 > 6.5 ng/ml had a worse 2-year survival rate than those with HE4 ≤ 6.5 ng/ml (58.9% vs 96.2%, p < 0.001).ConclusionsSerum levels of HE4 were elevated in IPAH patients and correlated with disease severity. HE4 was an independent predictor of clinical worsening in IPAH patients.

Cholesterol efflux capacity, HDL cholesterol, and risk of coronary heart disease: a nested case-control study in men

The capacity of HDLs to accept cholesterol effluxing from macrophages has been proposed as a new biomarker of HDLs' anti-atherogenic function. Whether cholesterol efflux capacity (CEC) is independent of HDL cholesterol (HDL-C) as a biomarker for coronary heart disease (CHD) risk in a generally healthy primary-prevention population remains unanswered. Therefore, in this nested case-control study, we simultaneously assessed CEC (using J774 cells) and plasma HDL-C levels as predictors of CHD in healthy middle-aged and older men not receiving treatment affecting blood lipid concentrations. We used risk-set sampling of participants free of disease at baseline from the Health Professionals Follow-Up Study, and matched cases (n = 701) to controls 1:1 for age, smoking, and blood sampling date. We applied conditional logistic regression models to calculate the multivariable relative risk and 95% CIs of CHD over 16 years of follow-up. CEC and HDL-C were correlated (r = 0.50, P < 0.0001). The risk (95% CI) of CHD per one SD higher CEC was 0.82 (0.71-0.96), but completely attenuated to 1.08 (0.85-1.37) with HDL-C in the model. The association per one SD between HDL-C and CHD (0.66; 0.58-0.76) was essentially unchanged (0.68; 0.53-0.88) after adjustment for CEC. These findings indicate that CEC's ability to predict CHD may not be independent of HDL-C in a cohort of generally healthy men.

Circulating Multiple Metals and Incident Stroke in Chinese Adults.

Background and Purpose- Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke. Methods- We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model. Results- The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13-1.46], 1.19 [95% CI, 1.05-1.35], and 1.30 [95% CI, 1.07-1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50-0.87] and 0.68 [95% CI, 0.51-0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20-1.56] and 1.53 [95% CI, 1.16-2.01]). Conclusions- Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.

Assessment of medication use during pregnancy by Web-based questionnaires, pharmacy records and serum screening

ObjectiveTo compare assessment of early pregnancy medication exposure using three methods of data collection. MethodsSerum samples were obtained from 752 women participating in the PRegnancy and Infant DEvelopment (PRIDE) Study before gestational week 17. For 52 women using medication at the date of blood sampling according to Web-based questionnaires or pharmacy records, we analysed serum samples using untargeted liquid chromatography time-of-flight spectrometry. ResultsMedication was detected in 18 serum samples (35%). Medications taken orally for chronic conditions reported in the questionnaire were detected in serum and vice versa. Pharmacy records did not identify additional exposed women, but missed exposure in 5 women mainly due to unavailability. We observed substantial discordance between the three methods for inhaled medication, dermatological preparations, and medications for short-term use, which went often undetected in serum. ConclusionsIt remains challenging to assess medication use in large-scale studies as no ‘gold standard’ is currently available.

Clinical adverse effects of Chemotherapy protocolusing 6-Mercaptopurine in Iraqi patients with Acute Lymphocytic Leukemia during Maintenance Phase

Clinical adverse effects of Chemotherapy protocolusing 6-Mercaptopurine in Iraqi patients with Acute Lymphocytic Leukemia during Maintenance Phase

Bone Turnover Markers Are Not Associated With Hip Fracture Risk: A Case-Control Study in the Women's Health Initiative

Current guidelines recommend that serum C-terminal telopeptide of type I collagen (CTX) and serum procollagen type 1 aminoterminal propeptide (PINP), measured by standardized assays, be used as reference markers in observational and interventional studies. However, there are limited data to determine whether serum CTX and PINP are associated with hip fracture risk among postmenopausal women. We determined the associations of serum CTX and serum PINP with hip fracture risk among postmenopausal women aged 50 to 79 years at baseline. We performed a prospective case-control study (400 cases, 400 controls) nested in the Women's Health Initiative Observational Study, which enrolled participants at 40 US clinical centers. Cases were women with incident hip fracture not taking osteoporosis medication; hip fractures were confirmed using medical records. Untreated controls were matched by age, race/ethnicity, and date of blood sampling. Serum CTX and serum PINP were analyzed on 12-hour fasting blood samples. The main outcome measure was incident hip fracture risk (mean follow-up 7.13 years). After adjustment for body mass index, smoking, frequency of falls, history of fracture, calcium and vitamin D intake, and other relevant covariates, neither serum CTX level nor serum PINP level was statistically significantly associated with hip fracture risk (CTX ptrend = 0.22, PINP ptrend = 0.53). Our results do not support the utility of serum CTX level or PINP level to predict hip fracture risk in women in this age group. These results will inform future guidelines regarding the potential utility of these markers in fracture prediction. © 2018 American Society for Bone and Mineral Research.

Seasonal variation of serum vitamin D levels in Romania

Romania is located in Eastern Europe, roughly between 44°N and 48°N latitude. Seasonal variation of serum vitamin D in Romanian subjects is unknown. We assessed the seasonal variation of 25-hydroxy vitamin D [25(OH)D] in Romanian population. We retrieved from our endocrinology center database all 25(OH)D measurements between 2012 and 2016. We also evaluated age, sex, diagnosis, and date of blood sampling. The 25(OH)D was measured by two different chemiluminescence or electrochemiluminescence assays. There were 8024 subjects (median age 50 (37, 62); 1429 men (17.8%)) without a diagnosis of low bone mass (osteopenia or osteoporosis). The median serum 25(OH)D was 18.6 (12.7, 25.4)ng/mL. Of the subjects, 0.73, 14.4, 55.6, and 86.1% had a serum 25(OH)D level below 4, 10, 20, and 30ng/mL, respectively. Serum 25(OH)D showed a marked seasonal variation with highest levels in September (24.1 [18.3, 30.3]ng/mL) and lowest levels in March (13.5 [9.4, 19.6]ng/mL) (p < 0.001). The seasonal variation (early autumn vs. early spring) persisted in all age and sex groups and was maximal for 21-40years of age (26.5 (20.8, 33.1) vs. 12.9 (9.7, 17.9)ng/mL) and minimal for >65years of age (18.6 (13.0, 27.2) vs. 12.7 (7.8, 19.7)ng/mL). Men and women showed similar amplitude of serum 25(OH)D variation. The prevalence of vitamin D deficiency is high, particularly in the elderly. The data show a strong seasonal variation of serum 25(OH)D in all subgroups of our Romanian population with highest levels in September and lowest levels in March.

Higher serum 25(OH)D concentrations are associated with improved FEV1 and FVC in adolescence.

Vitamin D plays a role in the development of the immune system and the lung, as well as in airway remodelling. Therefore, this study investigated the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and spirometric lung function parameters at age 15 years.In the German birth cohorts GINIplus and LISAplus, lung function testing by spirometry and 25(OH)D measurements were performed during the 15-year follow-up examinations. Valid lung function measurements pre- and/or post-bronchodilation and serum 25(OH)D concentrations, which were adjusted for the date of blood sampling to account for seasonal variability, were available for 2607 adolescents. Associations between 25(OH)D concentrations and spirometric parameters were analysed using generalised additive models adjusted for confounding factors.Serum 25(OH)D concentrations were significantly associated with forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC measured before bronchodilation after adjustment for potential confounders: FEV1 increased by 10 mL (95% CI 2-17), FVC by 20 mL (95% CI 12-28) and FEV1/FVC decreased by 0.177% (95% CI -0.286 to -0.067) per 10 nmol·L-1 increase in 25(OH)D concentrations. Flow rates (forced expiratory flow rates at 25, 50 and 75% of exhaled FVC (FEF25, FEF50, FEF75) and mean flow rate between 25 and 75% of FVC (FEF25-75)) were not associated with vitamin D.Similar associations were observed for lung function parameters measured after bronchodilation.Vitamin D concentrations are positively associated with volume-related lung function parameters pre- and post-bronchodilation, suggesting structural changes in peripheral airways.

High TCR Vbeta Skewing in CD4+ and Low in CD8+ Is Associated with Development of Chronic Graft-Versus-Host Disease

IntroductionChronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Perturbations in immune reconstitution following allo-HSCT are believed to be integral to the pathophysiology of cGVHD. We hypothesized that skewing in T cell repertoire around day 80 would be predictive of cGVHD, while maintenance of a broad repertoire would be protective. One method used to assess skewing is the Gini Index, a conventional measure of income inequality. In this prospective study, we utilized a rapid FACS based method of TCR Vβ repertoire analysis within CD4+ and CD8+ in patients at day 80-110 post allo-HSCT to determine whether preferential TCR skewing predicts the development of cGVHD.MethodsPeripheral blood samples were obtained from 79 consented patients at day 80-110 following allo-HSCT at The University of Texas MD Anderson Cancer Center from October 2012 to November 2015. All patients were in remission of their disease at the time of blood sampling. Fresh PBMC were analyzed by FACS after staining for CD3, CD4, CD8 and IOTest Beta Mark 24 TCR Vβ kit. The TCR Gini Index scores (GS) were calculated for the T cell subsets, and ranged from 0 to 100. Low GS indicate more equal distribution of TCR-Vβ families (i.e. broad repertoire), whereas high GS reflect unequal distribution of TCR-Vβ families (i.e. repertoire skewing). Predictive thresholds of GS were identified in quartiles analysis and confirmed by Receiver Operating Characteristic (ROC) curve.The association between GS and the rate of cGVHD since the date of blood sampling was evaluated using competing-risks regression analysis. The diagnosis of cGVHD was based on the 2014 National Institutes of Health guidelines.ResultsThe median age at transplant was 53 years (range 21-75) and 60% of patients were male. The most common transplant indication was AML/MDS (52%) followed by lymphoma (16%), ALL (14%), and other (18%). Graft source was peripheral blood (54%), bone marrow (43%) and umbilical cord blood (UCB) (3%) with donors being matched unrelated (65%), matched-related (24%), mismatch related (9%) and UCB (3%). Forty three (54%) patients were not in remission at the time of transplant. At the time of enrollment, 47% had history of grade II-IV acute GVHD and 44% were on systemic steroids. At a median follow up of 2 years since blood sampling, 16 patients developed cGVHD (cumulative incidence (CI) 23%; 95% Confidence Interval: 15-35). The median time from HSCT to cGVHD was 174 days (range 111-551 days). None of the clinical or demographic characteristics listed above, except history of acute GVHD, was significantly associated with the incidence of cGVHD. GS were significantly predictive of the incidence of cGVHD. The 2 year %CI of cGVHD was 47% in patients who had CD4+ TCR GS >55% (n=19) compared with 16% in those with CD4+ GS ≤55% (n=60) (hazard ratio (HR) =3.4, P=0.01). In contrast to CD4+, lower CD8+ GS predicted for higher incidence of cGVHD. The 2 year %CI of cGVHD was 39% in patients (n=34) with CD8+ GS ≤60% compared with 10% in patients (n=45) with CD8+ GS >60% (HR=4.5, P=0.009). When both CD4+ and CD8+ GS were considered in combination, the 2 year incidence of cGVHD was highest in patients (n=6) with both low CD8+ (≤60%) and high CD4+ (>55%) GS, and lowest in patients (n=32) with high CD8+ (>60%) and low CD4+ (≤55%) GS (%CI: 83% vs 4%, P=0.001). The combined effect of high CD4+ and low CD8+ TCR skewing was more pronounced in patients with a history of grade II-IV acute GVHD. Low CD8+ (≤60%, n=28) or high CD4+ (>55%, n=13) GS occurring separately were associated with comparable rates of cGVHD (%CI: 31% and 27%, p=0.8), irrespective of history of grade II-IV acute GVHD (Figure).ConclusionsHigh CD4+ and low CD8+ TCR Gini indices were independent predictors of cGVHD. Our results indicated that the higher skewing of CD8+ TCR appeared to be protective of cGVHD and the opposite for CD4+. Our study is the first to test the usefulness of FACS-based TCR measurement and Gini Index score in a clinical setting to help predict the development of cGVHD and provide greater insights into the pathogenesis of cGVHD. Using this convenient FACS-based method to identify patients who are at risk of developing cGVHD could be beneficial from development of effective preventive or therapeutic strategies. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Concentrations of Persistent Organic Pollutants in California Children's Whole Blood and Residential Dust.

We evaluated relationships between persistent organic pollutant (POP) levels in the blood of children with leukemia and POP levels in dust from their household vacuum cleaners. Blood and dust were collected from participants of the California Childhood Leukemia Study at various intervals from 1999 to 2007 and analyzed for two polybrominated diphenyl ethers (PBDEs), two polychlorinated biphenyls (PCBs), and two organochlorine pesticides using gas chromatography-mass spectrometry. Due to small blood sample volumes (100 μL), dichlorodiphenyldichloroethylene (DDE) and BDE-153 were the only analytes with detection frequencies above 70%. For each analyte, depending on its detection frequency, a multivariable linear or logistic regression model was used to evaluate the relationship between POP levels in blood and dust, adjusting for child's age, ethnicity, and breastfeeding duration; mother's country of origin; household annual income; and blood sampling date. In linear regression, concentrations of BDE-153 in blood and dust were positively associated; whereas, DDE concentrations in blood were positively associated with breastfeeding, maternal birth outside the U.S., and Hispanic ethnicity, but not with corresponding dust-DDE concentrations. The probability of PCB-153 detection in a child's blood was marginally associated with dust-PCB-153 concentrations (p = 0.08) in logistic regression and significantly associated with breastfeeding. Our findings suggest that dust ingestion is a source of children's exposure to certain POPs.

Epidemiological, Clinical and Entomological Characteristics of Yellow Fever Outbreak in Darfur 2012.

The study aims at analyzing the epidemiological, clinical and entomological characteristics of Darfur yellow fever epidemic. It is a descriptive, cross-sectional study. According to operational case definition, suspected yellow fever cases are included in case spread sheet with variables like age, sex, locality, occupation, status of vaccination, onset of symptoms, presenting symptoms, date of blood sampling and confirmation of diagnosis either by laboratory results or epidemiological link. Data about important entomological indices were collected by surveys conducted in 17 localities of 3 Darfur states (Central, West and south Darfur). All Darfur states (especially Central Darfur) have been affected by Yellow Fever outbreak. There is a need to review the non-specific case definition of Yellow Fever which seems to overwhelm the system during outbreaks with cases of other endemic diseases. The significant risk factors of this outbreak included male sex, adult age, outdoor occupation and traditional mining. The fatality rate was significantly associated with vaccination status. The highest fatality rate was recorded by children less than 2 years old (42.9%). Generally, increase in certain entomological indices was followed by increase in number of reported cases 7 days later. Central Darfur state was significantly higher in most studied entomological indices.

Air Pollution and Biomarkers of Systemic Inflammation and Tissue Repair in COPD Patients

The origin(s) of systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) is unclear. We investigated the impact of exposure to ambient air pollution on systemic biomarkers of inflammation (C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-6, IL-8 and fibrinogen) and tissue repair (hepatocyte growth factor (HGF)) in 242 clinically stable COPD patients (mean age 67.8 years and forced expiratory volume in 1 s 71.3% predicted) in Barcelona, Spain, in 2004-2006. A spatiotemporal exposure assessment framework was applied to predict ambient nitrogen dioxide (NO2) and levels of particles with a 50% cut-off aerodynamic diameter of 2.5 μm (PM2.5) at each participant's home address during 10 periods of 24 h (lags 1-10) and 1 year prior to the blood sampling date. We used linear regression models to estimate associations between biomarkers and exposure levels. An interquartile range (IQR) increase in NO2 exposure in lag 5 was associated with 51%, 10% and 9% increases in CRP, fibrinogen and HGF levels respectively. We also observed 12% and 8% increases in IL-8 associated with an IQR increase in NO2 exposure in lag 3 and over the year before sampling, respectively. These increases were larger in former smokers. The results for PM2.5 were not conclusive. These results show that exposure to ambient NO2 increases systemic inflammation in COPD patients, especially in former smokers.

First and second trimester maternal serum markers in pregnancies with a vanishing twin.

The aim of this study was to assess the concentration of the first and second trimester maternal serum markers in pregnancies with a vanishing twin. This is a retrospective case-control study of pregnancies screened for Down syndrome in one Ontario center. Singleton pregnancies with ultrasound evidence of a vanishing twin were identified, and each was matched with five normal singleton controls for ethnicity, maternal age, gestational age, and blood sampling date. The median MoM of the first and second trimester serum markers was compared between cases and controls. The differences were assessed using the Mann-Whitney U-test. The study included 174 pregnancies that had a vanishing twin. Compared with control pregnancies, pregnancy associated plasma protein A increased by 21% (p = 0.0026), alpha-fetoprotein (AFP) increased by 10% (p < 0.0001), and dimeric inhibin A (DIA) increased by 13% (p = 0.0470) in pregnancies with a vanishing twin. Unconjugated oestriol and total human chorionic gonadotrophin were not significantly changed in these pregnancies. Pregnancy associated plasma protein A is not an adequate marker for pregnancies with a vanishing twin. The impact of elevated AFP on risk estimation is offset by that of DIA to certain extent. Further studies are needed to establish an adequate adjustment method for AFP and DIA to improve the accuracy of screening results for these pregnancies.

Vitamin D Deficiency Is a Risk Factor for Adverse Graft Outcomes in Kidney Transplant Recipients (KTR).

It is now established that vitamin D is functionally pleiotropic with diverse functions. The influence of vitamin D deficiency on long-term outcomes in KTRs is not clear. In this study, we have analysed the independent impact of vitamin D deficiency on graft outcomes. 504 KTRs had their vitamin D levels checked in 2008. Vitamin D deficiency was defined as a level <50nmol/L as per WHO criteria. KTRs were followed up for 6 years from the date of blood sampling. In this population, the prevalence of vitamin D deficiency was high at 66.5% with a significantly higher prevalence in older (71.9% vs. 60.9%, P=0.006) and female recipients (male 62.1% vs. female 73.2%, P=0.006) and in relatively new transplants (recent transplants 72.3% vs. old transplants 60.6%, P=0.003). Not surprisingly mean PTH levels were significantly higher in KTRs with vitamin D deficiency and this was true in those with superior graft function (creatinine <130mmol/L) as well. KTRs who were vitamin D deficient had significantly worse overall (77% vs. 92%, P<0.0001) and death censored graft survival (89% vs. 96%, P=0.009) when compared to those with normal levels.Figure: No Caption available.In a stratified analysis, this was noted to be worse in KTRs on maintenance steroids, with relatively worse baseline renal function and proteinuria, with secondary hyperparathyroidism, deceased donor transplants and late vs. earlier transplants. In a multivariate Cox proportional hazard model, vitamin D deficiency was associated with significantly worse overall graft (HR 2.7, 95% CI 1.5-4.9, P=0.001) and death censored graft survival (HR 2.4, 95% CI 1.1-5.5, P=0.04) independent of age, PTH levels, gender, graft number, type of transplant, time since transplantation, graft type and renal function measured by both proteinuria and eGFR. In conclusion, vitamin D deficiency which is highly prevalent in KTRs is associated with adverse graft outcomes. This study raises an important question about the need for a prospective trial of vitamin D replacement in KTRs.

β2-microglobulin, cystatin C, and creatinine and risk of symptomatic peripheral artery disease.

Backgroundβ2‐Microglobulin and cystatin C may have advantages over creatinine in assessing risk associated with kidney function. We therefore investigated whether emerging filtration markers, β2‐microglobulin and cystatin C, are prospectively associated with risk of the development of peripheral artery disease (PAD).Methods and ResultsWe conducted nested case‐control studies among women within the Nurses’ Health Study (1990–2010) and among men within the Health Professionals Follow‐up Study (1994–2008) with the use of archived blood samples collected before PAD diagnosis. During follow‐up, symptomatic PAD was confirmed in 144 women and 143 men. Controls were matched 3:1 based on age, race, smoking status, fasting status, and date of blood sampling. Conditional logistic regression models were used to estimate relative risks (RRs) and were adjusted for plasma creatinine and cardiovascular risk factors. In women, the RRs (95% CI) per 1‐SD) increment were 1.16 (0.85 to 1.58) for β2‐microglobulin and 0.94 (0.69 to 1.28) for cystatin C. Corresponding RRs in men were 1.50 (1.08 to 2.09) for β2‐microglobulin and 1.54 (1.07 to 2.22) for cystatin C. There was no association between creatinine and PAD risk in women, whereas the association in men (RR 1.41, 95% CI 1.10 to 1.81) disappeared after adjustment for either β2‐microglobulin or cystatin C. In pooled analyses of men and women, only β2‐microglobulin was associated with PAD risk (RR 1.31, 95% CI 1.04 to 1.64).ConclusionsIn pooled analyses, β2‐microglobulin was associated with an increased risk of symptomatic PAD; a similar association with cystatin C was observed only in men. The findings suggest that β2‐microglobulin may capture the atherosclerosis‐promoting or atherosclerosis‐related elements of kidney dysfunction better than creatinine.