Importance of measuring pharmacologically active metabolites of edoxaban: development and validation of an ultra-high-performance liquid chromatography coupled with a tandem mass spectrometry method

Journal of Thrombosis and Thrombolysis - Although DOACs do not require regular measurements of their blood concentrations, clinical situations may require an assessment of their concentration....     

Dysregulation of the in vivo production of interleukin-1 receptor antagonist in patients with rheumatoid arthritis pathogenetic implications

Objective. Patients with rheumatoid arthritis (RA) have defective hypothalamic responses to inflammation, possibly because of excessive production of cytokine inhibitor, which could blunt the effects of cytokines on the hypothalamus, or because of an imbalance between interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra), which could create a mainly proinflammatory state. The present study was undertaken to investigate these possibilities. Methods. The in vivo kinetics of IL-1β and IL-1Ra secretion were studied in patients with RA, osteoarthritis (OA), and chronic osteomyelitis (OM), and in normal controls before and after surgery. Results. The 24-hour levels of IL-1Ra were significantly increased in RA (P < 0.001), but there was no diurnal variation in any group. Preoperative levels of IL-1Ra were higher in RA and OA sera (P = 0.001). After surgery, IL-1Ra behaved like an acute-phase reactant protein in all subjects. IL-1β was 10–20 times higher in RA than in OM and OA patients at baseline, but the percentage increase in all groups postoperatively was the same. RA patients had an IL-1Ra:IL-1β ratio of 26.2 ± 3.7 (mean ± SEM) at baseline (OM patients 89.2 ± 5.8 and OA patients 1,310 ± 363); this increased to 66.5 ± 19.8 after surgery (OM patients 120 ± 6.7 and OA patients 325.8 ± 106). Conclusion. RA patients have a dysregulation of IL-1Ra production, and it seems unlikely that the defective hypothalamic response seen in RA is due to a functional deficit of IL-1β.     

Analytical Sensitivity of Six SARS-CoV-2 Rapid Antigen Tests for Omicron versus Delta Variant

Rapid antigen detection (RAD) tests are commonly used for the diagnosis of SARS-CoV-2 infections. However, with the continuous emergence of new variants of concern (VOC), presenting various mutations potentially affecting the nucleocapsid protein, the analytical performances of these assays should be frequently reevaluated. One hundred and twenty samples were selected and tested with both RT-qPCR and six commercial RAD tests that are commonly sold in Belgian pharmacies. Of these, direct whole-genome sequencing identified the strains present in 116 samples, of which 70 were Delta and 46 were Omicron (BA.1 and BA.1.1 sub-lineages, respectively). The sensitivity across a wide range of Ct values (13.5 to 35.7; median = 21.3) ranged from 70.0% to 92.9% for Delta strains and from 69.6% to 78.3% for Omicron strains. When taking swabs with a low viral load (Ct > 25, corresponding to <4.9 log₁₀ copies/mL), only the Roche RAD test showed acceptable performances for the Delta strains (80.0%), while poor performances were observed for the other RAD tests (20.0% to 40.0%). All the tested devices had poor performances for the Omicron samples with a low viral load (0.0% to 23.1%). The poor performances observed with low viral loads, particularly for the Omicron strain, is an important limitation of RAD tests, which is not sufficiently highlighted in the instructions for use of these devices.     

TIPS for portal decompression to allow palliative treatment of adenocarcinoma of the esophagus

We describe a case in which a transjugular intrahepatic portosystemic shunt (TIPS) was inserted to enable palliative treatment of an adenocarcinoma of the esophagus. The cirrhotic patient presented with esophageal varices in contact with a tumor of the esophagus. By relieving portal pressure, TIPS reduced the risk of hemorrhage during laser resection and prevented recurrence of esophageal varices.     

Robotic versus laparoscopic distal pancreatectomy: a French prospective single-center experience and cost-effectiveness analysis

Surgical Endoscopy - Benefits and cost-effectiveness of robotic approach for distal pancreatectomy (DP) remain debated. In this prospective study, we aim to compare the short-term results and real...     

Sezary syndrome cells unlike normal circulating T lymphocytes fail to migrate following engagement of NT1 receptor

Circulating malignant Sezary cells are a clonal proliferation of CD4+CD45RO+ T lymphocytes primarily involving the skin. To study the biology of these malignant T lymphocytes, we tested their ability to migrate in chemotaxis assays. Previously, we had shown that the neuropeptide neurotensin (NT) binds to freshly isolated Sezary malignant cells and induces through NT1 receptors the cell migration of the cutaneous T cell lymphoma cell line Cou-L. Here, we report that peripheral blood Sezary cells as well as the Sezary cell line Pno fail to migrate in response to neurotensin although they are capable of migrating to the chemokine stromal-cell-derived factor 1 alpha. This is in contrast with normal circulating CD4+ or CD8+ lymphocytes, which respond to both types of chemoattractants except after ex vivo short-time anti-CD3 monoclonal antibody activation, which abrogates the neurotensin-induced lymphocyte migration. Furthermore, we demonstrate that neurotensin-responsive T lymphocytes express the functional NT1 receptor responsible for chemotaxis. In these cells, but not in Sezary cells, neurotensin induces recruitment of phosphatidylinositol-3 kinase, and redistribution of phosphorylated cytoplasmic tyrosine kinase focal adhesion kinase and filamentous actin. Taken together, these results, which show functional distinctions between normal circulating lymphocytes and Sezary syndrome cells, contribute to further understanding of the physiopathology of these atypical cells.     

Blinded, Externally Controlled Multicenter Evaluation of Light Microscopy and PCR for Detection of Microsporidia in Stool Specimens

The quality parameters for the detection of microsporidia in identical sets of 50 stool samples were determined for six laboratories where technicians used light microscopy and for six laboratories where technicians used PCR. The average overall sensitivities were 67% (89% for patient samples only) for the PCR laboratories and 54% (80% for patient samples only) for the light microscopy laboratories. Specificities were 98 and 95%, respectively. Differences in results were most apparent between the individual laboratories rather than between the two major methods used.