Analytical performance of eight enzymatic assays for ethanol in serum evaluated by data from the Belgian external quality assessment scheme.

OBJECTIVES: Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. METHODS: Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. RESULTS: A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using the 702 module, Thermo Scientific and Alinity c. Cobas 8000 using the c702 module showed the highest measurement uncertainty for lower concentrations. For higher concentrations, Alinity c, Thermo Scientific and Vitros were the methods with the highest measurement uncertainty. CONCLUSIONS: The bias of the enzymatic techniques is nearly negligible for all methods except Alinity c. Variability differs strongly between measurement procedures. This study shows that the Alinity c has a worse measurement uncertainty than other systems for concentrations above 0.5 g/L. Overall, we found the differences in measurement uncertainty to be mainly influenced by the differences in variability.

Suicide by vaping the synthetic cannabinoid 4F-MDMB-BINACA: cannabinoid receptors and fluoride at the crossroads of toxicity?

A 22-year-old man was hospitalized after stating he would 'commit suicide in a non-detectable way'. He was admitted with a severe necrotizing pancreatitis and acute kidney injury, evolving to multiple organ failure. His condition rapidly deteriorated, and he died 11 days after hospital admission. Postmortem histopathology confirmed fulminant necrotizing pancreatitis, acute tubular necrosis, cerebral edema, pericentral/midzonal hepatocellular necrosis and acute respiratory distress syndrome. Metabolites of 4F-MDMB-BINACA, a synthetic cannabinoid, were detected in urine and serum collected at hospital admission. The same drug was found in a vapor fluid found in the man's apartment. As cannabis use has been etiologically linked to acute pancreatitis, we hypothesize that the more afferent and potent 4F-MDMB-BINACA could induce acute pancreatitis via stimulation of cannabinoid (CB)1-receptors. Alternatively, terminal fluorination could have induced a dose-dependent toxic effect on a wide range of cellular processes, leading to cell dysfunction and death. This is the first clinicopathological description of a lethal intoxication with 4F-MDMB-BINACA, following extensive vaping. Toxic effects could either relate to CB-receptor binding or to direct fluoride toxicity.

Smartphone Application Monitoring of Acceleration Forces During Pneumatic Tube System Transport of Emergency Department Patient Samples.

BACKGROUND: The use of pneumatic tube system (PTS) transport has gained considerable popularity in modern hospitals but is also associated with sample hemolysis. The potential contribution of PTS-associated acceleration forces to high hemolysis rates observed in the emergency department (ED) has not been investigated before and can be easily examined nowadays using smartphone applications. The first aim of our study was to investigate whether our PTS induces hemolysis of patient samples obtained from our ED. We also explored a potential correlation between hemolysis index (HI) on the one hand and acceleration forces during PTS transport or other potential causes of hemolysis related to patient characteristics on the other for two different blood sampling techniques. METHODS: Blood samples from 100 ED patients were collected in one Sarstedt S-Monovette® serum tube (PTStransported to laboratory) and two BD Vacutainer® serum tubes (one PTS-transported and one hand-carried). For all serum samples HI was measured. A smartphone was sent along with the samples in order to register accelerations during transport. Patient's erythrocyte sedimentation rate (ESR), mean corpuscular volume (MCV), hematocrit, total cholesterol, low density lipoprotein (LDL), and high-density lipoprotein (HDL) concentration were determined as well. RESULTS: Hemolysis rate was only 1 - 4% and 5% for PTS and hand-carried transport, respectively. Calculated acceleration vector sums for PTS transport from the ED to laboratory reached up to 131.49 m/second2 (13.40 g). No correlation could be demonstrated between HI on the one hand and acceleration forces acting on the samples during PTS transport or ESR, MCV, hematocrit, and HDL concentration on the other. However, an inverse correlation was noted between HI and cholesterol (total and LDL) concentration in serum tubes transported via PTS, though not in those carried by hand. CONCLUSIONS: We demonstrated that our PTS does not induce or contribute to hemolysis of ED patient samples, even at high acceleration vector sums up to 13 g. Technological advancements such as the development of smartphone applications offer the ability to regularly monitor acceleration forces during PTS transport of patient samples. Low total cholesterol and LDL concentrations may affect the erythrocyte membrane fluidity, making erythrocytes more prone to hemolysis.

High anion gap metabolic acidosis induced by cumulation of ketones, L- and D-lactate, 5-oxoproline and acute renal failure.

INTRODUCTION: Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed. CASE PRESENTATION: A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus, underwent gastric bypass surgery in the past and was chronically treated with high doses of paracetamol and fosfomycin. Urosepsis was diagnosed, whilst laboratory analysis of serum bicarbonate concentration and calculation of the anion gap indicated a  HAGMA. L-lactate, D-lactate, ß-hydroxybutyric acid, acetone and 5-oxoproline serum levels were markedly elevated and renal function was impaired. DISCUSSION: We concluded that this case of HAGMA was induced by a variety of underlying conditions: sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion and paracetamol intake. Risk factors for 5-oxoproline intoxication present in this case are female gender, sepsis, impaired renal function and uncontrolled type 2 diabetes mellitus. Furthermore, chronic antibiotic treatment with fosfomycin might have played a role in the increased production of 5-oxoproline. CONCLUSION: Paracetamol-induced 5-oxoproline intoxication should be considered as a cause of HAGMA in patients with female gender, sepsis, impaired renal function or uncontrolled type 2 diabetes mellitus, even when other more obvious causes of HAGMA such as lactate, ketones or renal failure can be identified.

Causes, consequences and management of sample hemolysis in the clinical laboratory.

Preanalytical hemolysis of blood samples is a common problem in medical practice, especially in emergency departments. Several potential influences on sample hemolysis have been investigated, including sampling techniques, centrifugation and sample transport. In particular, the use of intravenous catheters and the vacuum sampling technique have often been demonstrated to provoke hemolysis. Other factors playing a role include the use of inappropriate puncture sites, complicated blood sampling, prolonged tourniquet application, underfilling of tubes and excessive shaking of specimens. Training of phlebotomists can play a pivotal role in overcoming these issues. A sample may also undergo hemolysis at the point of centrifugation, more specifically when centrifugation lasts too long or is done repeatedly. Pneumatic tube system (PTS)-transported samples tend to be more strongly affected by hemolysis compared to hand-carried ones, though whether this difference is clinically relevant remains questionable. The velocity at which the sample moves, the distance it covers and the shock forces it sustains all determine to what extent hemolysis occurs during PTS transport. The use of cushion inserts in the carrier to stabilize the samples and the presence of a gel separator in the transported serum tubes may prevent PTS-induced hemolysis. Finally, there is considerable variation between patients in the extent to which samples are prone to hemolysis. Sample hemolysis leads to unreliable laboratory results, delayed diagnosis and patients suffering avoidable discomfort. Specifically, hemolysis may interfere with laboratory results due to release of intracellular components, dilution effects, proteolysis and interference with analytical techniques. There is ongoing debate about how laboratories should deal with results altered by hemolysis. Laboratory specialists should clearly communicate with the ordering clinicians in order to make an informed decision about how to interpret hemolysis-affected analytical results. This review looks into current evidence concerning the causes and consequences of in vitro hemolysis, and aims to explain how to deal with it.

Lower Serum Zinc and Higher CRP Strongly Predict Prenatal Depression and Physio-somatic Symptoms, Which All Together Predict Postnatal Depressive Symptoms.

Pregnancy and delivery are associated with activation of immune-inflammatory pathways which may prime parturients to develop postnatal depression. There are, however, few data on the associations between immune-inflammatory pathways and prenatal depression and physio-somatic symptoms. This study examined the associations between serum zinc, C-reactive protein (CRP), and haptoglobin at the end of term and prenatal physio-somatic symptoms (fatigue, back pain, muscle pain, dyspepsia, obstipation) and prenatal and postnatal depressive and anxiety symptoms as measured using the Edinburgh Postnatal Depression Scale (EPDS), Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), and Spielberger's State Anxiety Inventory (STAI). Zinc and haptoglobin were significantly lower and CRP increased at the end of term as compared with non-pregnant women. Prenatal depression was predicted by lower zinc and lifetime history of depression, anxiety, and premenstrual tension syndrome (PMS). The latter histories were also significantly and inversely related to lower zinc. The severity of prenatal EDPS, HAMD, BDI, STAI, and physio-somatic symptoms was predicted by fatigue in the first and second trimesters, a positive life history of depression, anxiety, and PMS, and lower zinc and higher CRP. Postnatal depressive symptoms are predicted by prenatal depression, physio-somatic symptoms, zinc and CRP. Prenatal depressive and physio-somatic symptoms have an immune-inflammatory pathophysiology, while postnatal depressive symptoms are highly predicted by prenatal immune activation, prenatal depression, and a lifetime history of depression and PMS. Previous episodes of depression, anxiety disorders, and PMS may prime pregnant females to develop prenatal and postnatal depressive symptoms via activated immune pathways.

Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods.

BACKGROUND: This is a retrospective study on a large hospital database to establish age- and sex-related mean values and reference ranges for serum creatinine (Scr), obtained with an IDMS-traceable, enzymatic method, in a Caucasian population. METHODS: The database was filtered for unique entries to reduce the presence of correlated and pathological data. Three different statistical methods, a non-parametric method, the Bhattacharya procedure and a non-linear fit of the cumulative Gaussian distribution were used to estimate the serum creatinine-age dependency for men and women, from birth till 100 years of age. RESULTS: Scr increases with age, equal for boys and girls, up to 14 years and with a much steeper slope for boys than for girls between 14 and 20 years. We show that the Scr-age pattern is constant between 20 and 70 years with a mean of 0.90 mg/dL [0.63-1.16 mg/dL] for men and 0.70 mg/dL [0.48-0.93 mg/dL] for women. Above 70, Scr starts to slowly increase again. CONCLUSIONS: Indirect methods confirm the available reference intervals from healthy-volunteer studies and add information on age-periods not covered by these studies. As such, indirect methods can be used complementary to healthy-volunteer studies.

Haemostatic changes and acquired activated protein C resistance in normal pregnancy.

Influence of changes in levels of coagulation factors and anticoagulants on acquired activated protein C (APC) resistance were studied in 40 healthy women during normal pregnancy. Factor VIII (FVIII), von Willebrand factor antigen (VWF:Ag), free protein S (FPS) and protein C were determined at 5-13, 14-26 and 27-40 weeks gestation and more than 6 weeks postpartum. APC anticoagulant activity was determined by measuring the activated partial thromboplastin time before and after adding human APC, expressed as the APC-sensitivity ratio (APC-SR). During the second and third gestation trimesters a significant increase (P < 0.05) in FVIII and VWF:Ag levels and a decrease in FPS levels were seen compared with the first trimester. Postpartum FVIII and VWF:Ag levels significantly decreased and FPS levels increased compared with the third trimester. Protein C levels remained unchanged during pregnancy and postpartum. Between increased FVIII and lowered APC-SR a trend of inverse correlation (r = -0.329; P = 0.076) occurred in the second trimester. No correlation was found between APC-SR and FPS or VWF:Ag levels. A remarkable finding is the strong inverse relationship between APC-SR and protein C levels (r