Monitoring Variability of Laboratory Results in a Clinical Data Warehouse Using Automatic Dashboard.

Hospital laboratory results are a significant data source in Clinical Data Ware-houses (CDW). To ensure comparability across healthcare organizations and for use in research studies, the results need to be interoperable. The LOINC (Logical Observation Identifiers, Names, and Codes) terminology provides a unique identifier for local codes for lab tests, enabling interoperability. However, in real-world, events occur over time and can disrupt the distribution of lab result values. For example, new equipment may be added to the analysis pipeline, a machine may be replaced, formulas may evolve due to new scientific knowledge, and legacy terminologies may be adopted. This article proposes a pipeline for creating an automated dashboard to monitor these events and data quality. We used automatic change point detection methods such as PELT for event detection in lab results. For a given LOINC code, we create a dashboard that summarizes the number of local codes mapped, and the number of patients (by sex, age, and hospital service) associated with the code. Finally, the dashboard enables the visualization of time events that disrupt the signal distribution. The biologists were able to explain to us the changes for several biological assays.

Enteral citrulline supplementation versus placebo on SOFA score on day 7 in mechanically ventilated critically ill patients: the IMMUNOCITRE randomized clinical trial.

BACKGROUND: Restoring plasma arginine levels through enteral administration of L-citrulline in critically ill patients may improve outcomes. We aimed to evaluate whether enteral L-citrulline administration reduced organ dysfunction based on the Sequential Organ Failure Assessment (SOFA) score and affected selected immune parameters in mechanically ventilated medical intensive care unit (ICU) patients. METHODS: A randomized, double-blind, multicenter clinical trial of enteral administration of L-citrulline versus placebo for critically ill adult patients under invasive mechanical ventilation without sepsis or septic shock was conducted in four ICUs in France between September 2016 and February 2019. Patients were randomly assigned to receive enteral L-citrulline (5 g) every 12 h for 5 days or isonitrogenous, isocaloric placebo. The primary outcome was the SOFA score on day 7. Secondary outcomes included SOFA score improvement (defined as a decrease in total SOFA score by 2 points or more between day 1 and day 7), secondary infection acquisition, ICU length of stay, plasma amino acid levels, and immune biomarkers on day 3 and day 7 (HLA-DR expression on monocytes and interleukin-6). RESULTS: Of 120 randomized patients (mean age, 60 ± 17 years; 44 [36.7%] women; ICU stay 10 days [IQR, 7-16]; incidence of secondary infections 25 patients (20.8%)), 60 were allocated to L-citrulline and 60 were allocated to placebo. Overall, there was no significant difference in organ dysfunction as assessed by the SOFA score on day 7 after enrollment (4 [IQR, 2-6] in the L-citrulline group vs. 4 [IQR, 2-7] in the placebo group; Mann‒Whitney U test, p = 0.9). Plasma arginine was significantly increased on day 3 in the treatment group, while immune parameters remained unaffected. CONCLUSION: Among mechanically ventilated ICU patients without sepsis or septic shock, enteral L-citrulline administration did not result in a significant difference in SOFA score on day 7 compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02864017 (date of registration: 11 August 2016).

[Molecular basis of hyperammonemia secondary to asparaginase: from therapeutic efficacity to toxicity]. / Bases moléculaires de l'hyperammoniémie sous asparaginase : de l'efficacité thérapeutique à la toxicité.

Asparaginase is a key molecule in the treatment of acute lymphoblastic leukemia. It has improved response rates to chemotherapy. However, this is not without consequences. Therapeutic efficacy is sometimes achieved at the expense of toxicities that can lead to treatment discontinuation. Among them, patients can develop hyperammonemia which can sometimes be symptomatic leading to neurological disorders that can go as far as hyperammonemic coma or even death. Through a review of the current state of the literature, the objective is to understand the disparity of ammonia values as well as the clinical heterogeneity for a given ammonia concentration. A review of the literature including more than eighty publications was performed. The glutaminase activity of asparaginase seems to play an important role in the development of hyperammonia. At present, no risk factors have been identified for the development of hyperammonemia. On the other hand, the question of the impact of pre-analysis phase arises. Indeed, asparaginase continues to exert its activity in vitro, which leads to an artefactual increase in ammonia.

Avoiding falsely low creatinine concentrations measured in patients treated with N-acetylcysteine for acetaminophen intoxication using enzymo-amperometric method - An in vitro and in vivo study.

BACKGROUND: Circulating creatinine is a biomarker of paramount importance in clinical practice. In cases of acetaminophen (APAP) intoxication, the antidote, N-acetylcysteine (NAC), interferes with commonly used creatininase-peroxidase methods. This study aimed to assess whether creatininase-amperometric methods were affected in this context. METHODS: This study includes in vitro interference tests, involving four creatinine assays using NAC-spiked plasma pools and an in vivo retrospective study comparing creatininase-peroxidase and creatininase-amperometric measurements in patients presenting with NAC-treated APAP poisoning. RESULTS: Creatininase-peroxidase method was impacted by NAC interference in a clinically-significant manner at therapeutic NAC levels (basal value recovery of 80 % and 70 % for 500 and 1000 mg.L-1 of NAC, respectively), surpassing the desirable Reference Change Value (RCV%). Enzymo-amperometric methods were not impacted. Among patients, a mean bias of -45.2 ± 28.0 % was observed for the peroxidase detection method compared to the amperometric in those who received NAC prior plasma sampling and -2.7 ± 5.4 % in those who did not. CONCLUSIONS: Our findings indicate that enzymo-amperometric creatinine assays remain unaffected by NAC interference due to the absence of the peroxidase step in the analytical process. Therefore, these methods are suitable to prevent spurious hypocreatininemia in APAP intoxicated patients undergoing NAC therapy.

[A case of lipidogram abnormality on post-surgical abdominal drain fluid]. / Un cas d'anomalie du lipidogramme sur liquide de drain abdominal post-chirurgical.

A 63-years-old man with a history of metastatic neuroendocrine tumor of the small bowel was admitted to hospital for laparoscopic lumpectomy. Following surgery, two drains were placed, one opposite the removal of the pancreatic lesions and the other opposite the hepatic lumpectomy site. A lipidogram on the drain fluids is requested for chylomicron, triglyceride and lipase determination.

Early detection of plasma d-lactate: Toward a new highly-specific biomarker of bacteraemia?

Background: Bloodstream infections are a leading cause of mortality. Their detection relies on blood cultures (BCs) but time to positivity is often between tens of hours and days. d-lactate is a metabolite widely produced by bacteria but very few in human. We aimed to evaluate d-lactate, d-lactate/l-lactate ratio and d-lactate/total lactate ratio in plasma as potential early biomarkers of bacteraemia on a strictly biological standpoint. Methods: A total of 228 plasma specimens were collected from patients who had confirmed bacteraemia (n = 131) and healthy outpatients (n = 97). Specific l-lactate and d-lactate analyses were performed using enzymatic assays and analytical performances of d-lactate, d-lactate/total lactate and d-lactate/l-lactate ratios for the diagnosis of bacteraemia were assessed. Results: A preliminary in vitro study confirmed that all strains of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were able to produce d-lactate at significant levels. In patients, plasma d-lactate level was the most specific biomarker predicting a bacteraemia profile with a specificity and predictive positive value of 100% using a cut-off of 131 µmol.L-1. However, sensitivity and negative predictive value were rather low, estimated at 31% and 52%, respectively. d-lactate displayed an Area Under Receiver Operating Characteristic (AUROC) curve of 0.696 with a P value < 0.0001. There was no difference of d-lactate levels between BCs bottles positive for Gram-positive or Gram-negative bacteria (p = 0.55). Conclusion: d-lactate shows promise as a specific early biomarker of bacterial metabolism. The development of rapid automated assays could raise clinical applications for infectious diseases diagnosis including early bacteraemia prediction.

Newborn Screening of Primary Carnitine Deficiency: An Overview of Worldwide Practices and Pitfalls to Define an Algorithm before Expansion of Newborn Screening in France.

Primary Carnitine Deficiency (PCD) is a fatty acid oxidation disorder that will be included in the expansion of the French newborn screening (NBS) program at the beginning of 2023. This disease is of high complexity to screen, due to its pathophysiology and wide clinical spectrum. To date, few countries screen newborns for PCD and struggle with high false positive rates. Some have even removed PCD from their screening programs. To understand the risks and pitfalls of implementing PCD to the newborn screening program, we reviewed and analyzed the literature to identify hurdles and benefits from the experiences of countries already screening this inborn error of metabolism. In this study, we therefore, present the main pitfalls encountered and a worldwide overview of current practices in PCD newborn screening. In addition, we address the optimized screening algorithm that has been determined in France for the implementation of this new condition.

MONOCYTIC MYELOID-DERIVED SUPPRESSOR CELL EXPANSION AFTER CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS INDUCES LYMPHOCYTE DYSFUNCTION.

ABSTRACT: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an immune paresis that predisposes to the development of postoperative infections and sepsis. Among factors responsible for CPB-induced immunosuppression, circulating myeloid-derived suppressor cells (MDSCs) have been found to induce early lymphocyte apoptosis and lymphocyte proliferation inhibition. However, the mechanisms involved are not fully understood. In this study, we found that the main lymphocyte subsets decreased significantly 24 h after cardiac surgery with CBP. As expected, cardiac surgery with CPB induced a monocytic MDSC expansion associated with an increased T-cell apoptosis and decreased proliferation capacity. Noteworthy, granulocytic MDSCs remain stable. Myeloid-derived suppressor cell depletion restored the ability of T-cell to proliferate ex vivo . After CPB, indoleamine 2,3-dioxygenase activity and IL-10 plasma level were increased such as programmed death-ligand 1 monocytic expression, whereas plasma level of arginine significantly decreased. Neither the inhibition of indoleamine 2,3-dioxygenase activity nor the use of anti-programmed death-ligand 1 or anti-IL-10 blocking antibody restored the ability of T-cell to proliferate ex vivo . Only arginine supplementation restored partially the ability of T-cell to proliferate.