Defining trimester-specific reference intervals for carbohydrate deficient transferrin in pregnant women.

OBJECTIVES: Extensive consumption of alcohol during pregnancy can lead to severe complications for the unborn child. Carbohydrate-deficient transferrin (CDT) levels in serum have become a common biomarker for excessive alcohol intake. However, during pregnancy CDT levels can rise to levels above commonly used cut-off values, for reasons unrelated to alcohol intake. The aim of this study is to investigate the changes in CDT values during pregnancy and to determine accurate, trimester dependent reference intervals. METHODS: 439 serum samples of 147 healthy pregnant women were obtained for trimester 1, 2, 3, and post-partum and were analysed by high-performance liquid chromatography (HPLC) and an N-Latex immunonephelometric assay. New trimester-specific reference intervals were established. RESULTS: This study demonstrates there is a trimester-dependent increase of %CDT, as up to 39.4% of the population exceeded the previously established upper reference limit of 1.7%. In our study the estimated upper reference limit for %DST/%CDT were 1.55%, 1.96%, 2.05% and 1.35% for trimester 1, 2, 3 and post-partum for the HPLC-method and 2.02%, 2.19%, 2.19% and 1.96% for the N-Latex immunoassay. CONCLUSIONS: We demonstrate that CDT levels rise during pregnancy. The magnitude of the increase is method-dependent and needs to be taken into account. We have established method- and trimester-specific reference intervals to prevent false-positive results in alcohol abuse screening tests during pregnancy.

Exploratory analysis of interleukin-38 in hospitalized COVID-19 patients.

INTRODUCTION: A major contributor to coronavirus disease 2019 (COVID-19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin-38 (IL-38) is an IL-1 family member with broad anti-inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL-38 in COVID-19 patients in comparison to healthy controls, whereas two other studies report no differences in IL-38 concentrations. METHODS: Here, we present an exploratory, retrospective cohort study of circulating IL-38 concentrations in hospitalized COVID-19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age- and sex-matched healthy subjects. Plasma IL-38 concentrations were measured by enzyme-linked immunosorbent assay, disease-related proteins by proximity extension assay, and clinical data were retrieved from hospital records. RESULTS: IL-38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL-38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL-38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL-38 and the inflammatory biomarker d-dimer was observed in men of the validation cohort. In women of the validation cohort, IL-38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL-38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL-10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein. CONCLUSIONS: These data indicate that IL-38 is not associated with disease outcomes in hospitalized COVID-19 patients. However, moderate correlations between IL-38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL-38 concentrations are not indicative of COVID-19 severity, its anti-inflammatory effects may reduce COVID-19 severity and should be experimentally investigated.

Reference intervals and longitudinal changes in copeptin and MR-proADM concentrations during pregnancy.

BACKGROUND: Vasopressin and adrenomedullin and their stable by-products copeptin and midregional part of proadrenomedullin (MR-proADM) are promising biomarkers for the development of preeclampsia. However, clinical use is hampered by the lack of trimester-specific reference intervals. We therefore estimated reference intervals for copeptin and MR-proADM in disease-free Dutch women throughout pregnancy. METHODS: Apparently healthy low risk pregnant women were recruited. Exclusion criteria included current or past history of endocrine disease, multiple pregnancy, use of medication known to influence thyroid function and current pregnancy as a result of hormonal stimulation. Women who miscarried, developed hyperemesis gravidarum, hypertension, pre-eclampsia, hemolysis elevated liver enzymes and low platelets, diabetes or other disease, delivered prematurely or had a small for gestational age neonate were excluded from analyses. Blood samples were collected at 9-13 weeks (n=98), 27-29 weeks (n=94) and 36-39 weeks (n=91) of gestation and at 4-13 weeks post-partum (PP) (n=89). Sixty-two women had complete data during pregnancy and PP. All analyses were performed on a Kryptor compact plus. RESULTS: Copeptin increases during pregnancy, but 97.5th percentiles remain below the non-pregnant upper reference limit (URL) provided by the manufacturer. MR-proADM concentrations increase as well during pregnancy. In trimesters 2 and 3 the 97.5th percentiles are over three times the non-pregnant URL provided by the manufacturer. CONCLUSIONS: Trimester- and assay-specific reference intervals for copeptin and MR-proADM should be used. In addition, consecutive measurements and the time frame between measurements should be considered as the differences seen with or in advance of preeclampsia can be expected to be relatively small compared to the reference intervals.

TSH and fT4 during pregnancy: an observational study and a review of the literature.

BACKGROUND: Trimester-specific reference intervals for TSH are recommended to assess thyroid function during pregnancy due to changes in thyroid physiology. Laboratories should verify reference intervals for their population and assay used. No consistent upper reference limit (URL) for TSH during pregnancy is reported in literature. We investigated the use of non-pregnant reference intervals for TSH, recommended during pregnancy by current Dutch guidelines, by deriving trimester-specific reference intervals in disease-free Dutch pregnant women as these are not available. METHODS: Apparently healthy low risk pregnant women were recruited via midwifery practices. Exclusion criteria included current or past history of thyroid or other endocrine disease, multiple pregnancy, use of medication known to influence thyroid function and current pregnancy as a result of hormonal stimulation. Women who were TPO-antibody positive, miscarried, developed hyperemesis gravidarum, hypertension, pre-eclampsia, HELLP, diabetes or other disease, delivered prematurely or had a small for gestational age neonate were excluded. Blood samples were collected at 9-13 weeks (n=99), 27-29 weeks (n=96) and 36-39 weeks (n=96) of gestation and at 4-13 weeks post-partum (n=95). Sixty women had complete data during pregnancy and post-partum. All analyses were performed on a Roche Cobas e601 analyser. RESULTS AND CONCLUSIONS: In contrast to current Dutch guidelines, the 97.5th percentiles of TSH in the first (3.39 mIU/L) and second trimesters (3.38 mIU/L) are well under the non-pregnant URL of 4.0 mIU/L. The higher TSH in the third trimester (97.5th percentile 3.85 mIU/L) is close to the current non-pregnant URL of 4.0 mIU/L. Absolute intra-individual TSH is relatively stable during pregnancy and post-partum as individuals tracked within the tertile assigned in trimester 1. Even small deviations within the population reference interval may indicate subtle thyroid dysfunction.

Procalcitonin in the recognition of complications in critically ill surgical patients.

BACKGROUND: Procalcitonin (PCT) is a relatively new, promising indirect parameter for infection. In the intensive care unit (ICU) it can be used as a marker for sepsis. However, in the ICU there is a need for reliable markers for clinical deterioration in the critically ill patients. This study determines the clinical value of PCT concentrations in recognizing surgical complications in a heterogeneous group of general surgical patients in the ICU. MATERIAL AND METHODS: We prospectively collected PCT concentration data from April 2010 to June 2012 for all general surgical patients admitted to the ICU. Both the relationships between PCT levels and events (diagnostic and therapeutic interventions) as well as between PCT levels and surgical complications (abscesses, bleeding, perforation, ischemia, and ileus) were studied. RESULTS: PCT concentrations were lower in patients who developed complications than those who did not develop complications on the same day, although not significant (P = 0.27). A 10% increase in PCT levels resulted in a 2% higher complication odds, but again this was not significant (odds ratio [OR], 1.020; 95% confidence interval [CI], 0.961-1.083; P = 0.51). Even a 20% or 30% increase in PCT concentrations did not result in higher complication probability (OR, 1.039; 95% CI, 0.927-1.165 and OR, 1.057; 95% CI, 0.897-1.246). Furthermore, an increase in PCT levels did not show an increase or a reduction in the number of diagnostic and therapeutic interventions. CONCLUSIONS: An increase in PCT levels does not help to predict surgical complications in critically ill surgical patients.

Determining the clinical value of lactate in surgical patients on the intensive care unit.

BACKGROUND: The purpose of this study is first to assess the clinical value of lactate concentrations by comparison with clinical scoring systems, and second to determine the value of lactate levels in clinical decisions as ordering diagnostic and therapeutic (re)interventions in the population of critically ill surgical patients on the intensive care unit (ICU). MATERIALS AND METHODS: From April 2010 to June 2011, the L-lactate concentrations, Sequential Organ Failure Assessment (SOFA) score and Acute Physiological and Chronic Health Evaluation II (APACHE II) score were prospectively collected in surgical patients (n = 174) admitted into the ICU. The L-Lactate and scoring systems were related to events defined as performing computed tomography-scans, laparotomy, ultrasonography, and flexible endoscopy. Furthermore, all surgical complications were also registered. RESULTS: For SOFA scores above four points, mean lactate concentrations increased 4.5% for each point increase in SOFA score (P < 0.0005). In APACHE II scores above 16 points, mean lactate concentrations increased 2.9% for each point increase in APACHE II score (P < 0.0005). Each 10% increase in lactate concentration showed a 3.3% higher odds for a first event (OR 1.033; P = 0.26). Lactate levels did not correspond with more complications (OR 0.968; P = 0.52). CONCLUSIONS: There is a significant positive relationship between lactate concentrations, high SOFA scores, and APACHE II scores. However, the important outcome is that lactate seems to be a poor predictor for surgical complications in the critically ill surgical patient in the ICU.

The role of C-reactive protein and the SOFA score as parameter for clinical decision making in surgical patients during the intensive care unit course.

INTRODUCTION: C-reactive Protein (CRP) is used next to clinical scoring systems to recognize critically ill patients prone to develop complications on the Intensive Care Unit (ICU). The purpose of this study is to assess the predictive value of CRP as parameter for clinical deterioration and/or clinical decision making as ordering diagnostic procedures or performing (re)interventions. Also, we wanted to determine the value of CRP in early detection of surgical complications in the critically ill general surgical patient in the ICU and its interpretation in adjunct to a clinical scoring system, the Sequential Organ Failure Assessment Score. MATERIALS AND METHODS: In our prospective observational study, 174 general surgical patients admitted into the Intensive Care Unit were included. We evaluated the Sequential Organ Failure Assessment Score (SOFA) and daily measured the C-reactive protein (CRP) concentrations. All events (diagnostic or therapeutic interventions) and surgical complications were registered. Then the relationship between SOFA score, CRP concentrations, events and complications were studied. RESULTS: Each 10% increase in CRP resulted in a 3.5% increase in the odds of an event (odds ratio 1.035, 95% CI: 1.004-1.068; p = 0.028). However, an increase in CRP levels did not lead to a higher odds of complication (OR 0.983, 95% CI: 0.932-1.036; p = 0.52). When adjusting for the SOFA score the effect of CRP on the probability of a first event remained significant (OR 1.033, 95% CI: 1.001-1.065; p = 0.046), and again did not significantly affect the complication probability (OR 0.980, 95% CI: 0.929-1.035; p = 0.46). CONCLUSIONS: An increase in C-reactive protein is a poor parameter for early detection of complications in the critically ill surgical patient in the ICU by means of diagnostic procedures or therapeutic (re)-interventions.

[A boy with jaundice]. / Een jongetje met icterus.

A 1-year-old Moroccan boy was referred because of jaundice. A peripheral blood smear showed 'blister cells'. This finding is characteristic for haemolysis caused by glucose-6-phosphate dehydrogenase deficiency. It appeared hemolysis occurred because the boy ate fava beans.