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The article discusses the biochemical screening of glucose-6-phosphate dehydrogenase (G6PD) deficiency in borderline cases, highlighting the importance of detecting heterozygotes who may have moderately decreased enzyme activities. The study conducted at a reference laboratory in France showed that measuring additional enzymes like pyruvate kinase or hexokinase significantly improved the detection of heterozygotes. The research suggests that using a three-enzyme approach can enhance the sensitivity of G6PD deficiency screening, especially in identifying heterozygotes, while also acknowledging the limitations in detecting certain variants. [Extracted from the article]

Aims Methods and results Conclusion We sought to characterize the clinical course of patients following worsening heart failure (WHF) treated in an outpatient setting and to identify factors associated with a poor response to standard of care with loop diuretics.Between September 2022 and March 2023, 44 eligible patients (mean age 66.3 years, 84% male) with ejection fraction <50% and with WHF symptoms in the preceding week treated in an outpatient setting were enrolled. Patients were assessed weekly over 4 weeks following the WHF episode. At week 4, responses to fluid expansion and furosemide administration were assessed in 39 patients to unmask persistent subclinical congestion. Patients were on stable doses of guideline‐directed medical therapy (GDMT) with a mean daily furosemide dose of 47.4 mg. Patient‐reported and physician‐assessed symptoms and quality of life improved over the 4 weeks. At 1 h following 1 L Ringer solution infused over 2 h, the median (interquartile range) urine volume and urine sodium excreted over 3 h were 300 (200.0–500.0) ml and 39.6 (12.4–63.0) mEq, respectively. Receiver‐operating characteristic curves suggest that cystatin C >1.2 ng/ml, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) >1500 pg/ml, and high‐sensitivity troponin T >20 pg/ml represent good predictors of non‐response to a fluid challenge (diuresis, natriuresis, and rales) following an outpatient WHF, with having all three markers associated with the worst response.Patients with high levels of troponin, or NT‐proBNP, or cystatin C who develop WHF despite being treated with a loop diuretic, need novel therapies for WHF. [ABSTRACT FROM AUTHOR]

The diagnosis of subarachnoid hemorrhage (SAH) is extremely important for appropriate management. Cerebral computed tomography (CT), used as the first-line investigation to detect bleeding, has excellent sensitivity if performed promptly, but its sensitivity falls sharply with the time elapsed since the onset of SAH. Oxyhemoglobin and bilirubin, the breakdown products of heme, are detectable in cerebrospinal fluid (CSF) by spectrophotometric absorption, which defines the search for xanthochromia pigment in CSF. Both parameters can be sought when imaging is negative or doubtful with a strong suspicion of SAH based on clinical signs. In this context, our working group at the Société Française de Biologie Clinique (SFBC) is proposing recommendations to provide medical biologists with support for the implementation and validation of "oxyhemoglobin and bilirubin in CSF" test and enabling them to play their part in the diagnostic process. From the pre-analytical stages through to the delivery of results, we will summarize the pitfalls to be avoided, the main decision values and different physiological and pathological profiles.

Purpose: Congenital disorders of glycosylation (CDG) are one of the fastest growing groups of inborn errors of metabolism. Despite the availability of next-generation sequencing techniques and advanced methods for evaluation of glycosylation, CDG screening mainly relies on the analysis of serum transferrin (Tf) by isoelectric focusing, HPLC or capillary electrophoresis. The main pitfall of this screening method is the presence of Tf protein variants within the general population. Although reports describe the role of Tf variants leading to falsely abnormal results, their significance in confounding diagnosis in patients with CDG has not been documented so far. Here, we describe two PMM2-CDG cases, in which Tf variants complicated the diagnostic., Experimental Design: Glycosylation investigations included classical screening techniques (capillary electrophoresis, isoelectric focusing and HPLC of Tf) and various confirmation techniques (two-dimensional electrophoresis, western blot, N-glycome, UPLC-FLR/QTOF MS with Rapifluor). Tf variants were highlighted following neuraminidase treatment. Sequencing of PMM2 was performed., Results: In both patients, Tf screening pointed to CDG-II, while second-line analyses pointed to CDG-I. Tf variants were found in both patients, explaining these discrepancies. PMM2 causative variants were identified in both patients., Conclusion and Clinical Relevance: We suggest that a neuraminidase treatment should be performed when a typical CDG Tf pattern is found upon initial screening analysis., (© 2023 Wiley-VCH GmbH.)

Alanine (ALT) and aspartate aminotransferases (AST) are intracellular enzymes involved in the metabolism of amino acids. The measurements of their activities are two of the most ordered tests in clinical laboratories, used to screen, diagnose and follow diseases affecting the liver. Recent works highlighted that reference values for ALT and AST vary according to the analytical method and the individual’s characteristics, like with many other biomarkers. Reference values for ALT show clinically significant differences according to the analytical method (higher when supplementing samples with phosphate pyridoxal), gender (higher in males than in females), body mass index (positive correlation), and age (higher in infants and the elderly), but not according to ethnicity or employed analyzer. According to the analytical method and age, reported reference values for AST show clinically significant differences, similar to ALT. These observations prove clinical laboratories’ interest in updating their reference values according to sex, body mass index, age (especially when providing testing to pediatric or elderly populations), and the analytical method employed. If possible, a standardized method should be used, including sample supplementation with pyridoxal phosphate, to ensure the comparability of results between laboratories.

Covid-19 is responsible for myocardial injury in many infected patients, which is associated with severe disease and critical illness. The mechanisms by which SARS-CoV-2 may cause myocardial damage involve direct effect of the virus in cardiac cells and indirect effect due to the clinical consequences of Covid-19. Cardiomyocytes are well known to express Angiotensin-Converting Enzyme-2 receptors (ACE-2) to facilitate the virus cell entry, which could explain the occurrence of myocarditis, functional alterations in the myocardium, and more rarely, myocardial infarction. Myocardial injury may also be secondary to systemic inflammation or coagulopathy due to complicated Covid-19. The existence of a cardio-intestinal axis with alteration of tryptophan metabolism in the small bowel leading first to colitis and then to systemic inflammation has also been evoked to explain the myocardial injury. Morphological and metabolic disturbances of the heart during the Covid-19 are associated with elevated concentrations of cardiac blood biomarkers, mainly troponins and natriuretic peptides. The determination of these biomarkers has proven to be very useful for diagnosis, prognosis, and risk stratification. Indeed, recent data demonstrated that about 20% of infected patients admitted to the hospital have elevated troponin or BNP levels, and Covid-19 patients with elevated troponin concentrations beyond the diagnostic threshold (99th percentile) were associated with a higher risk of in-hospital mortality. In conclusion, after more than a year of a unique global pandemic, it is now clearly established that myocardial injury during Covid-19 is frequent and strongly contributes to the severity of the disease. Cardiac alterations secondary to direct infection of cardiac cells by SARS-CoV-2 or to the clinical consequences of Covid-19 are associated with elevated levels of cardiac biomarkers in blood, whose measurement is crucial in clinical decision making.