Anemia, Hepcidin, and Vitamin D in Healthy Preterm Infants: A Pilot Study.

OBJECTIVE: The etiology of anemia in premature neonates is multifactorial and may involve anemia of inflammation mediated by hepcidin. Hepcidin expression is suppressed by vitamin D. We aimed to investigate the interrelationship between hepcidin, anemia, and vitamin D status in preterm infants. STUDY DESIGN: Preterm infants aged 1 to 5 weeks were prospectively recruited at the neonatal intensive care unit of the Dana Dwek Children Hospital. Blood counts and serum levels of hepcidin, ferritin, iron, 25-hydroxyvitamin D [25(OH)D] and C-reactive protein (CRP) were measured and compared between anemic and nonanemic preterm infants. RESULTS: Forty-seven preterm infants (mean ± standard deviation gestational age at birth 32.8 ± 1.1 weeks, 66% males) were recruited. In total, 36% of the preterm infants were vitamin D deficient [25(OH)D < 20 ng/mL] and 15% were anemic. Hepcidin levels were significantly higher in anemic premature infants than in the nonanemic group (55.3 ± 23.9 ng/mL vs. 30.1 ± 16.3 ng/mL, respectively, p < 0.05). No differences were found in iron, ferritin, 25(OH)D, and CRP levels between anemic and nonanemic premature newborn infants. A positive correlation was found between hepcidin and ferritin (R 2 = 0.247, p = 0.02) and a negative correlation was found between 25(OH)D and CRP (R 2 = 0.1, p = 0.04). No significant correlations were found between 25(OH)D and hepcidin, iron, ferritin, or CRP. CONCLUSION: Anemia of prematurity was associated with high hepcidin serum levels. The exact mechanisms leading to anemia and the role of vitamin D warrant further investigation. KEY POINTS: · Hepcidin levels were significantly higher in anemic premature infants.. · A positive correlation was found between hepcidin and ferritin.. · Negative correlation was found between 25(OH)D and CRP..

Pathogenic heparin-induced thrombocytopenia and thrombosis (HIT) antibodies determined by rapid functional flow cytometry.

OBJECTIVES: Reliable diagnosis of heparin-induced thrombocytopenia and thrombosis (HIT) is mandatory for patient management, yet prompt determination of pathogenic antibodies remains an unmet clinical challenge. Common immunoassays carry inherent limitations and functional assays which detect antibody-mediated platelet activation are not usually readily available to routine laboratories, especially the serotonin release assay (SRA), being technically demanding, time consuming, and requires high level expertise. To overcome some of these limitations, we have developed a practical functional flow cytometric assay (FCA) for routine clinical use. METHODS: A simple FCA is described which avoids platelet manipulation, is highly specific and sensitive compared with SRA, and provides rapid results. RESULTS: Of the 650 consecutive samples, from HIT-suspected patients, 99 (15.3%) were positive by the PaGIA Heparin/PF4 immunoassay and 31 (4.8%) by FCA. Average platelet activation was 11-fold higher in PaGIA+/FCA+ vs PaGIA-/FCA- samples. Of 21 SRA-positive samples, 19 were FCA-positive (relative sensitivity 90.5%), and of 42 SRA-negative samples, 40 were FCA-negative (relative specificity 95.2%). The FCA showed significantly higher correlation with the clinical presentation of HIT (4Ts score) performed on 182 patients, compared with PaGIA Heparin/PF4 (ROC-plot analysis, AUC 0.93 vs 0.63, P < 0.001). At a 92% sensitivity, the assay specificity was 96%. CONCLUSIONS: The present FCA is practical for routine testing, providing prompt reliable results for initial diagnosis and confirmation, to effectively assist in HIT patient management.

Vitamin D Decreases Hepcidin and Inflammatory Markers in Newly Diagnosed Inflammatory Bowel Disease Paediatric Patients: A Prospective Study.

BACKGROUND AND AIMS: The role of hepcidin in inflammatory bowel disease [IBD] in children with anaemia is poorly understood. However, it has been shown that vitamin D suppresses hepcidin expression. We aimed to assess serum hepcidin levels and the effect of vitamin D treatment on those levels in newly diagnosed IBD paediatric patients. METHODS: Eighty-five children were prospectively recruited in the Dana-Dwek Children's Hospital [40 newly diagnosed IBD, 45 healthy controls, 47% female, mean age 13.5 ± 3.4 years]. Blood samples for measurement of interleukin 6 [IL-6], C-reactive protein [CRP], hepcidin, iron parameters and 25-hydroxyvitamin D [25-(OH)-D] levels were obtained at baseline. Patients with mild-to-moderate signs and symptoms of IBD were treated with 4000 units of vitamin D daily for 2 weeks, after which the blood tests were repeated. RESULTS: Basal hepcidin, IL-6, CRP and platelet counts were significantly higher, and haemoglobin, serum iron and transferrin levels were significantly lower in the IBD children compared to controls [p < 0.001]. Eighteen patients completed 2 weeks of treatment with vitamin D. Following treatment, serum 25-(OH)-D concentrations increased by 40% [from 22.5 to 32.5 ng/mL], and serum hepcidin, CRP and ferritin levels decreased by 81%, 81% and 40% [from 33.9 to 6.7 ng/mL, from 23.9 to 4.7 mg/L, and from 27 to 16 ng/mL, respectively] [p ≤ 0.001]. CONCLUSION: Serum hepcidin levels were significantly higher in IBD paediatric patients compared to controls. Following vitamin D treatment, serum hepcidin concentration decreased significantly. These findings suggest a potential role for vitamin D in treating anaemia in IBD children. CLINICALTRIALS.GOV NUMBER: NCT03145896.

The interrelationship between hepcidin, vitamin D, and anemia in children with acute infectious disease.

BACKGROUND: Hepcidin is a master regulator of iron metabolism. Recently, it has been shown that vitamin D suppresses hepcidin expression. Our hypothesis was that hepcidin levels inversely correlate with vitamin D levels in anemic children during acute infection. METHODS: A prospective study was performed on 90 patients (45 females, 45 males, mean age 7.3 ± 5 years) who were admitted to the pediatric ward. Sixty-two patients had infectious disease (32 with coexisting anemia, 30 without anemia), and 28 patients were hospitalized for noninfectious causes. Blood samples for IL-6, hepcidin, iron status parameters, and 25-hydroxyvitamin D (25-OHD) were obtained within 72 h after admission. RESULTS: Serum concentrations of IL-6 and hepcidin were significantly higher and 25-OHD, iron, and transferrin were significantly lower in anemic children with infectious disease compared with controls. Children with a serum 25-OHD level < 20 ng/ml had significantly increased odds of having anemia than those with a level > 20 ng/ml (OR: 6.1, CI: 1.15-32.76). Correlation analyses found positive associations between hepcidin levels and ferritin (R2 = 0.47, P < 0.001) and negative associations between hepcidin and transferrin (R2 = 0.57, P < 0.001). CONCLUSION: Higher IL-6 and lower 25-OHD levels may lead to higher hepcidin levels and subsequently to hypoferremia and anemia in children with acute infection.

Prolonged activation of the coagulation system during in vitro fertilization cycles.

OBJECTIVE: To investigate coagulation system changes during an in-vitro fertilization (IVF) cycle using Thromboelastogram (TEG) that enables analysis of the elastic properties of whole blood samples and provides a global assessment of the hemostatic function. STUDY DESIGN: A prospective study. TEG indices were evaluated in 23 women who underwent controlled ovarian stimulation for IVF at four points in time: 1. At the beginning of the cycle (corresponding to the lowest levels of E2), 2. On the day of hCG administration (maximal stimulation with highest E2 levels), 3. On the day of ovum pickup and 4. At the first pregnancy test (approximately 14days after ovum pickup). The main outcome measures were TEG indices including R-time (time until initial fibrin formation), K-time (time until a 20mm amplitude is achieved), α angle (the rate of clot formation), Maximum Amplitude (MA, strength of the fibrin clot), Coagulation Index (CI, calculated overall indicator of coagulation) and LY30 (the decrease in graph amplitude). RESULTS: R, K, α angle, MA and CI before hCG administration and at the time of the first pregnancy test were significantly higher compared to the baseline measurement before gonadotropins administration. No correlation was found between E2 and TEG indices. CONCLUSION: Ovarian stimulation is associated with prolonged increased coagulability that extends after the time of maximal ovarian stimulation. The lack of association between E2 levels and TEG indices suggest that additional factors may play a role in the pathogenesis of increased coagulability in women with ovarian stimulation.

A New Perspective on the Risk of Hypercoagulopathy in Ovarian Hyperstimulation Syndrome Using Thromboelastography.

Thromboelastography (TEG) provides real-time assessment of hemostasis by measuring the viscoelastic properties, coagulation factor, and platelet activity in whole blood samples. In this prospective case-control study, we wanted to investigate whether blood clot formation assessment, using TEG, can identify a hypercoagulable state in women with severe ovarian hyperstimulation syndrome (OHSS). Thirty-six women who were hospitalized with severe OHSS were allocated to the OHSS group and 32 women undergoing controlled ovarian hyperstimulation but who did not develop OHSS were allocated to the control group. The TEG indices were compared between women with severe OHSS and controls. All the coagulation indices assessed by TEG were significantly different in the OHSS group compared to the controls, depicting a hypercoagulable state. Median coagulation index was 3.6 (interquartile range: 2.80-4.15) and 1.45 (interquartile range: 0.20-2.30) in study group and controls, respectively ( P < .001). Our results show that TEG can be used to depict a hypercoagulable state in women with severe OHSS.

Absolute nucleated red blood cells counts do not predict the development of bronchopulmonary dysplasia.

OBJECTIVE: We tested the hypothesis that infants with bronchopulmonary dysplasia (BPD) have higher absolute nucleated red blood cells (aNRBCs) counts at birth than controls as a proxy measurement of exposure to intrauterine hypoxia. METHODS: We studied 39 preterm infants with BPD and compared them to 39 pair-matched controls without BPD. Criteria for exclusion in both groups included factors that may influence the aNRBCs at birth. RESULTS: In logistic regression, when pre-eclampsia, birthweight, gender, antenatal steroid therapy, 1-min Apgar scores, respiratory distress syndrome (RDS) (or surfactant use), intraventricular hemorrhage of grade 3 or more, nosocomial sepsis, patent ductus arteriosus, and aNRBC counts (or lymphocyte counts) were used as independent variables, and BPD as the dependent variable, only RDS (or its proxy measurement of surfactant use) and nosocomial sepsis remained included in the final analysis. CONCLUSIONS: aNRBC counts and lymphocyte counts do not appear to be elevated in infants that develop BPD, as compared to pair-matched controls without BPD. We speculate that chronic intrauterine hypoxia does not appear to play a major role in the pathogenesis of BPD. In contrast, postnatal events such as RDS and nosocomial sepsis appear to play a determining role in the pathogenesis of BPD.

Measurement of lymphocyte aggregation by flow cytometry-physiological implications in chronic lymphocytic leukemia.

BACKGROUND: Cellular aggregation is a physiological response of lymphocytes to various extracellular stimuli. Currently, lymphocytes aggregation is only evaluated qualitatively or by semiquantitative methods. In this study, we assessed the capacity of flow cytometry to measure lymphocytes aggregation in a quantitative, accurate, and reproducible manner, and examined the significance of aggregation responses in various lymphoproliferative diseases. METHODS: Extracellular triggers such as anti-CD19 antibodies or phorbol ester were utilized to induce lymphoid cells aggregation in a concentration dependent manner. Aggregation was quantified by flow cytometry based on the forward or side scatter (SSC), or by dark-field SSC of aggregates measured by ImageStreamX. Accuracy, reproducibility, and limitations of the methodology were evaluated. Aggregation responses were measured in various types of lymphoproliferative diseases, and correlated with immunophenotyping and IGHV mutational status in chronic lymphocytic leukemia. RESULTS: Lymphoid aggregates provoked by extracellular stimuli elevate the forward and SSC signals relatively to the number of cells in each event. Aggregation responses vary among different types of lymphoproliferative diseases. Moreover, elevated levels of CD19-induced aggregation are associated with aberrant chronic lymphocytic leukemia characteristics, but not with IGHV mutational status of the disease CONCLUSIONS: We have demonstrated that flow cytometry can provide accurate and reproducible measurement of both primary as well as T and B cell lines aggregation in response to extracellular stimuli. The use of quantitative evaluation of activation driven or other cellular aggregation may provide an analytical tool to elucidate biochemical and molecular mechanisms associated with lymphoproliferative diseases. © 2015 International Clinical Cytometry Society.

International Society for Cell Therapy Facility Sanitization Survey Laboratory Practices Committee Report.

BACKGROUND AIMS: Quality cell manufacturing processes require a clean laboratory environment. METHODS: This report was aimed at describing current cleaning and sanitization practices reported by facilities that manufacture many types of cellular therapy products for clinical use. It is our hope that this report may provide the groundwork for guidance recommendations directed at developing consensus standards for cleaning and sanitization practices across the globe. Facility sanitization is a central issue to regulatory and accreditation bodies. Facilities are required to develop plans to assess sanitization practices and test cleaning effectiveness. RESULTS: This document provides information on how this is performed in different facilities and may allow newer, smaller or less developed facilities to build, enhance or revise their current quality program by using experience and expertise in facility sanitization reported herein. CONCLUSIONS: This report summarizes the results of the latest survey and compares results with those previously reported. New and relevant trends in the field provide important information and will provide important information for establishing guidelines.

Integration of automated morphological features resolves a distinct group of atypical chronic lymphocytic leukemias with chromosomal aberrations.

Automated morphological assessment of peripheral blood slides has become an important modality facilitating characterization and quantification of cells in a uniform, fast and robust manner. In this study, we evaluated the morphological diversity in peripheral blood films of 94 chronic lymphocytic leukemia (CLL) patients using the DM1200 CellaVision automated microscopy system. Aberrant lymphocytes and smudge cells were enumerated and correlated with CLL immunophenotype, chromosomal aberrations and prognostic parameters. Herein, we show that the percentages of aberrant and smudge cells was highly variable between patients and did not correlate with each other. Increased aberrant lymphocytes and fewer smudge cells were associated with an atypical immunophenotype including low expression of CD23, higher levels of FMC7 and bright surface levels of CD20. High fraction of aberrant lymphocytes also was associated with trisomy 12. These cells were predominantly of small/medium size, sometimes with cleft nuclei. No correlation was noted between aberrant or smudge cells and clinical stage, CD38, ZA70 or time to first treatment. Taken together, automated morphological analysis of peripheral blood leukocytes emerged as a powerful and robust tool for the quantitative morphological stratification of CLL. Integration of the automated morphological features discriminates between different CLL phenotypes and distinct chromosomal aberrations.

Absolute monocyte count trichotomizes chronic lymphocytic leukemia into high risk patients with immune dysregulation, disease progression and poor survival.

Peripheral absolute monocyte count (AMC) has been reported to correlate with clinical outcome in different types of cancers. This association may relate to alteration in circulating monocytic subpopulations and tumor infiltrating macrophages. In this study we evaluated the clinical significance of peripheral AMC in 80 treatment naive patients with CLL. Measurement of AMC was based on direct morphological enumeration, due to our findings that complete blood count data may yield incorrect monocytes enumeration values in CLL. The median AMC in patients with CLL was within normal limits, however the AMC range exceeded the values of healthy individuals. The AMC trichotomized patients into 3 distinct sub-groups with different characteristics and outcomes. High AMC patients were younger and had higher absolute lymphocytes count, while patients with low AMC had prominent immune dysregulation (lower serum IgA levels, susceptibility to infections and a tendency for positive direct anti-globulin test). The low and high AMC patients had a shorter time to treatment compared to the intermediates AMC subgroups, whereas low AMC was associated with increased mortality caused by infectious complications. In conclusion, AMC quantification during the disease course classifies CLL patients into subgroups with unique clinical features and outcomes.

Platelet inhibitory effect of clopidogrel in patients treated with omeprazole, pantoprazole, and famotidine: a prospective, randomized, crossover study.

BACKGROUND: Concerns about an inhibitory effect of proton pump inhibitors (PPIs) on clopidogrel metabolism have been raised. Because the pharmacological effect of clopidogrel is dependent on genetically determined activity of the hepatic cytochrome P450 isoenzymes system, it is important to examine the interaction between different PPIs and high on-treatment platelet reactivity (HPR) after controlling for genetic variability. The aim of the study was to assess the effect of 2 PPIs and a histamine-2 (H2) receptor-blocker on platelet reactivity in a crossover trial where each patient was alternately treated with each drug. HYPOTHESIS: Omeprazole reduces HPR more than other PPI or H2 blockers. METHODS: Patients treated with aspirin and clopidogrel for at least 1 month were assigned to 3 consecutive 1-month treatment periods during which they were treated with each of the 3 study medications twice daily: omeprazole 20 mg, famotidine 40 mg, and pantoprazole 20 mg. At the end of each treatment phase, platelet function was evaluated with the Verify Now system using 2 cutoff values (>208 P2Y12 reaction units [PRUs] and >230 PRUs) for the definition of HPR. RESULTS: Patients with HPR were older than those without HPR (62 ± 10 vs 55 ± 8 years, respectively, P = 0.03). HPR was more prevalent during omeprazole therapy compared to famotidine or pantoprazole (48%, 33%, and 31%, respectively, for the 208 PRU cutoff, P= 0.04; and 37%, 17%, and 23%, respectively, for the 230 PRU cutoff, P= 0.003). CONCLUSIONS: After eliminating the effects of interindividual variability in clopidogrel metabolism, omeprazole therapy was associated with substantially more HPR than famotidine or pantoprazole.

Advances in megakaryocytopoiesis and thrombopoiesis: from bench to bedside.

Megakaryocytopoiesis involves the commitment of haematopoietic stem cells, proliferation and terminal differentiation of megakaryocytic progenitors (MK-p) and maturation of megakaryocytes (MKs) to produce functional platelets. This complex process occurs in specialized niches in the bone marrow where MKs align adjacent to vascular endothelial cells, form proplatelet projections and release platelets into the circulation. Thrombopoietin (THPO, TPO) is the primary growth factor for the MK lineage and necessary at all stages of development. THPO is constitutively produced in the liver, and binds to MPL (c-Mpl) receptor on platelets and MKs. This activates a cascade of signalling molecules, which induce transcription factors to drive MK development and thrombopoiesis. Decreased turnover rate and platelet number result in increased levels of free THPO, which induces a concentration-dependent compensatory response of marrow-MKs to enhance platelet production. Newly developed thrombopoietic agents operating via MPL receptor facilitate platelet production in thrombocytopenic states, primarily immune thrombocytopenia. Other drugs are available for attenuating malignant thrombocytosis. Herein, we review the regulation of megakaryocytopoiesis and platelet production in normal and disease states, and the innovative drugs and therapeutic modalities to stimulate or decrease thrombopoiesis.

Divergence in CD19-mediated signaling unfolds intraclonal diversity in chronic lymphocytic leukemia, which correlates with disease progression.

Emerging data on intraclonal diversity imply that this phenomenon may play a role in the clinical outcome of patients with chronic lymphocytic leukemia (CLL), where subsets of the CLL clone responding more robustly to external stimuli may gain a growth and survival advantage. In this study, we report intraclonal diversity resolved by responses to CD19 engagement in CLL cells, which can be classified into CD19-responsive (CD19-R) and -nonresponive subpopulations. Engagement of CD19 by anti-CD19 Ab rapidly induced cellular aggregation in the CD19-R CLL cells. The CD19-R CLL cells expressed higher surface levels of CD19 and c-myc mRNA, exhibited distinct morphological features, and were preferentially abolished in rituximab-treated patients. Both subpopulations reacted to sIgM stimulation in a similar manner and exhibited similar levels of Akt and Erk phosphorylation, pointing to functional signaling divergence within the BCR. CD19 unresponsiveness was partially reversible, where nonresponding CD19 cells spontaneously recover their signaling capacity following incubation in vitro, pointing to possible in vivo CD19-signaling attenuating mechanisms. This concept was supported by the lower CD19-R occurrence in bone marrow-derived samples compared with cells derived from the peripheral blood of the same patients. CLL patients with >15.25% of the CD19-R cell fraction had a shorter median time to treatment compared with patients with <15.25% of CD19-R cell fraction. In conclusion, divergence in CD19-mediated signaling unfolds both interpatient and intraclonal diversity in CLL. This signaling diversity is associated with physiological implications, including the location of the cells, their responses to anti-CLL therapeutics, and disease progression.

Increased CD39 expression on CD4(+) T lymphocytes has clinical and prognostic significance in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) cells depend on their microenvironment for proliferation and survival. Ectonucleotidase CD39 has anti-inflammatory properties as it hydrolyzes proinflammatory extracellular ATP, generates anti-inflammatory adenosine, and also protects regulatory T cells from ATP-induced cell death. In this study, we investigated the clinical significance of CD39 expression on CD4(+) T cells in 62 patients with CLL as well as its compartmental regulation and explored the possible mechanisms for its induction. Compared to healthy individuals, CD4(+)CD39(+) lymphocytes were increased in the peripheral blood of patients with CLL and correlated with the advanced stage of disease. CD4(+)CD39(+) cells were also higher in patients with CLL, who needed therapeutic intervention, and in those who had unmutated immunoglobulin heavy chain variable region gene, were ZAP70(+) or had ß2-microglobulin levels of >3 g/L. There were more CD4(+)CD39(+) lymphocytes in the bone marrow compartment than in the peripheral blood, and in vitro studies showed that CD39 can be induced on CD4(+) cells by exposure to ATP or indirectly, following B cell receptor engagement. This may support the notion that the leukemic cells contribute to create an immune-subversive environment, and perhaps to a poorer prognosis. CD39(+) may also serve as a future target for the development of novel therapies with immune-modulating antitumor agents in CLL.

Severe pregnancy complications are associated with elevated factor VIII plasma activity.

The objective of this study is to investigate the prevalence of elevated factor VIII activity among women with severe complications of pregnancy. The study group included 49 patients with a previous history of pregnancy complications: severe preeclampsia (n = 9); intrauterine fetal death (IUFD) (n = 9); severe intrauterine fetal growth restriction (IUGR) (n = 12); IUGR and preeclampsia (n = 7); preeclampsia and placental abruption (n = 2); IUFD and IUGR (n = 5); and abruptio placenta (n = 5). The control group included 49 healthy women who had had at least one normal pregnancy. Seventeen women of the study group (34.6%) had elevated factor VIII activity compared to one woman (2.1%) in the control group (P < 0.05). The mean level of factor VIII was 159 ± 52% and 88 ± 17.4% of normal activity (mean  ±  SD, t-test, P < 0.05). Importantly, 10 women of the study group (20.4%) had only elevated factor VIII activity with no other known thrombophilia compared to one woman (2.1%) in the control group (P < 0.05). Elevated plasma activity of factor VIII might be a risk factor for severe pregnancy complications.

Increased fibrosis progression rates in hepatitis C patients carrying the prothrombin G20210A mutation.

AIM: To examine whether hepatitis C virus (HCV)-infected patients who carry hypercoagulable mutations suffer from increased rates of liver fibrosis. METHODS: We analyzed DNA samples of 168 HCV patients for three common hypercoagulable gene mutations: prothrombin 20210 (PT20210), factor V Leiden (FV Leiden) and methylene tetrahydrofolate reductase (MTHFR). The patients were consecutively recruited as part of the prospective "Fibroscore Study" in France. The effect of the various mutations on the rate of fibrosis was analyzed statistically and was correlated with epidemiological, clinical and biochemical data such as grade and stage of liver biopsies, patients' risk factors for liver cirrhosis, and timing of infection. RESULTS: Fifty two of the patients were categorized as "fast fibrosers" and 116 as "slow fibrosers"; 13% of the "fast fibrosers" carried the PT20210 mutation as compared with 5.5% of the "slow fibrosers", with an odds ratio of 4.76 (P = 0.033; 95% CI: 1.13-19.99) for "fast" liver fibrosis. Carriage of MTHFR or FV Leiden mutations was not associated with enhanced liver fibrosis. CONCLUSION: Carriage of the PT20210 mutation is related to an increased rate of liver fibrosis in HCV patients.

Maternal snoring during pregnancy is associated with enhanced fetal erythropoiesis--a preliminary study.

OBJECTIVE AND BACKGROUND: Snoring is common among pregnant women and early reports suggest that it may bear a risk to the fetus. Increased fetal erythropoiesis manifested by elevated circulating nucleated red blood cells (nRBCs) has been found in complicated pregnancies involving fetal hypoxia. Both erythropoietin (EPO) and interleukin-6 (IL-6) mediate elevation of circulating nRBCs. The intermittent hypoxia and systemic inflammation elicited by sleep-disordered breathing (SDB) could affect fetal erythropoiesis during pregnancy. We hypothesized that maternal snoring will result in increased levels of fetal circulating nRBCs via increased concentrations of EPO, IL-6, or both. METHODS: Women of singleton uncomplicated full-term pregnancies were recruited during labor and completed a designated questionnaire. Umbilical cord blood was collected immediately after birth and analyzed for nRBCs, plasma EPO and plasma IL-6 concentrations. Newborn data were retrieved from medical records. RESULTS: One hundred and twenty-two women were recruited. Thirty-nine percent of women reported habitual snoring during pregnancy. Cord blood levels of circulating nRBCs, EPO and IL-6 were significantly elevated in habitual snorers compared with non-snorers (p = 0.03, 0.005 and 0.01; respectively). No differences in maternal characteristics or newborn crude outcomes were found. CONCLUSIONS: Maternal snoring during pregnancy is associated with enhanced fetal erythropoiesis manifested by increased cord blood levels of nRBCs, EPO and IL-6. This provides preliminary evidence that maternal snoring is associated with subtle alterations in markers of fetal well being.

The diagnostic yield of D-Dimer in relation to time from symptom onset in patients evaluated for venous thromboembolism in the emergency medicine department.

D-Dimer concentrations increase following the thrombotic event and decrease thereafter. Timing of D-Dimer evaluation in relation to the onset of the disease might have a diagnostic impact. We have presently performed a retrospective analysis of diagnostic procedures performed in individuals who presented to the Emergency department and evaluated for acute venous thromboembolism (VTE) following a single quantitative D-Dimer testing. Individuals who had a negative objective test served as controls to those who had a positive one (Doppler ultrasonography, high probability lung scan or a CT angiography). Seven hundred thirty-four individuals presented to the Emergency department, performed a single D-Dimer test as well as an objective test during their evaluation for an eventual event of acute VTE. One hundred ninety-seven patients had a positive objective test for either deep vein thrombosis (DVT) or pulmonary embolus. They were divided into seven tiles of times from symptoms onset. Highly significant differences between patients and controls regarding D-Dimer concentrations were noted mainly during the early days from symptom onset and turned less significant thereafter. Taking into consideration the time from symptoms onset in patients with acute VTE might have an effect on the diagnostic yield of quantitative D-Dimer in the Emergency department. We suggest not to exclude the eventual presence of acute VTE if quantitative D-Dimer is obtained later than 1 week following the onset of symptoms.