AKR1B10, One of the Triggers of Cytokine Storm in SARS-CoV2 Severe Acute Respiratory Syndrome.

Preventing the cytokine storm observed in COVID-19 is a crucial goal for reducing the occurrence of severe acute respiratory failure and improving outcomes. Here, we identify Aldo-Keto Reductase 1B10 (AKR1B10) as a key enzyme involved in the expression of pro-inflammatory cytokines. The analysis of transcriptomic data from lung samples of patients who died from COVID-19 demonstrates an increased expression of the gene encoding AKR1B10. Measurements of the AKR1B10 protein in sera from hospitalised COVID-19 patients suggests a significant link between AKR1B10 levels and the severity of the disease. In macrophages and lung cells, the over-expression of AKR1B10 induces the expression of the pro-inflammatory cytokines Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß) and Tumor Necrosis Factor a (TNFα), supporting the biological plausibility of an AKR1B10 involvement in the COVID-19-related cytokine storm. When macrophages were stressed by lipopolysaccharides (LPS) exposure and treated by Zopolrestat, an AKR1B10 inhibitor, the LPS-induced production of IL-6, IL-1ß, and TNFα is significantly reduced, reinforcing the hypothesis that the pro-inflammatory expression of cytokines is AKR1B10-dependant. Finally, we also show that AKR1B10 can be secreted and transferred via extracellular vesicles between different cell types, suggesting that this protein may also contribute to the multi-organ systemic impact of COVID-19. These experiments highlight a relationship between AKR1B10 production and severe forms of COVID-19. Our data indicate that AKR1B10 participates in the activation of cytokines production and suggest that modulation of AKR1B10 activity might be an actionable pharmacological target in COVID-19 management.

Organisation and quality monitoring for point-of-care testing (POCT) in Belgium: proposal for an expansion of the legal framework for POCT into primary health care.

BACKGROUND: There is a trend towards decentralisation of laboratory tests by means of Point-of-Care testing (POCT). Within hospitals, Belgian law requires a POCT policy, coordinated by the clinical laboratory. There is however no legal framework for POCT performed outside the hospital: no reimbursement, no compulsory quality monitoring and no limits nor control on the prices charged to the patient. Uncontrolled use of POCT can have negative consequences for individual and public health. PROPOSAL: We propose that POCT outside hospitals would only be reimbursed for tests carried out within a legal framework, requiring evidence-based testing and collaboration with a clinical laboratory, because clinical laboratories have procedures for test validation and quality monitoring, are equipped for electronic data transfer, are familiar with logistical processes, can provide support when technical issues arise and can organise and certify training. Under these conditions the government investment will be offset by health benefits, e.g. fall in antibiotic consumption with POCT for CRP in primary care, quick response to SARS-CoV2-positive cases in COVID-19 triage centres. PRIORITIES: 1° extension of the Belgian decree on certification of clinical laboratories to decentralised tests in primary care; 2° introduction of a separate reimbursement category for POCT; 3° introduction of reimbursement for a limited number of specified POCT; 4° setup of a Multidisciplinary POCT Advisory Council, the purpose of which is to draw up a model for reimbursement of POCT, to select tests eligible for reimbursement and to make proposals to the National Institute for Health and Disability Insurance (RIZIV/INAMI).

Leptomeningeal Carcinomatosis: A Call for Optimizing Diagnostic Sensitivity by the Hematology Laboratory.

In the cerebrospinal fluid (CSF), the demonstration of malignant cells by cytological examination is currently the gold standard for the diagnosis of leptomeningeal carcinomatosis (LC). However, a positive cytology is observed in only 50-60% of patients with LC and highly dependent on pre-analytical factors. The hematology laboratory could provide an immediate and accurate diagnosis, but diagnostic sensitivity is not always optimized once the sample is received. We hereby report a 49-year-old woman with a 3-year grade III invasive ductal carcinoma who was admitted to the emergency department due to headaches, nausea, and vomiting. The CSF revealed pleocytosis with suspicious high fluorescent cells on the hematology analyzer concomitantly with biochemical alterations. Cytomorphological examination confirmed tumor cells, thus diagnosing a leptomeningeal metastasis of her breast cancer. The patient was eventually transferred to palliative care. Cytological examination is a valuable tool for a rapid diagnosis of LC if diagnostic performance is optimized. In addition to repeated CSF collections with a sufficient volume (5-10 mL), this could be reached by processing the CSF as soon as possible, taking into account the fluorescence information from the analyzer, proceeding systematically to microscopic examination even with normal CSF white blood cell count, and providing quality improvement of the staff to identify malignant cells.