High plasma soluble CLEC-2 level predicts oxygen therapy requirement in patients with COVID-19.

Predicting the clinical course and allocating limited medical resources appropriately is crucial during the COVID-19 pandemic. Platelets are involved in microthrombosis, a critical pathogenesis of COVID-19; however, the role of soluble CLEC-2 (sCLEC-2), a novel platelet activation marker, in predicting the prognosis of COVID-19 remains unexplored. We enrolled 108 patients with COVID-19, hospitalized between January 2021 and May 2022, to evaluate the clinical use of sCLEC-2 as a predictive marker. sCLEC-2 levels were measured in plasma sampled on admission, as well as interleukin-6, cell-free DNA, von Willebrand factor, and thrombomodulin. We retrospectively classified the patients into two groups - those who required oxygenation during hospitalization (oxygenated group) and those who did not (unoxygenated group) - and compared their clinical and laboratory characteristics. The correlation between sCLEC-2 and the other parameters was validated. The sCLEC-2 level was significantly higher in the oxygenated group (188.8 pg/mL vs. 296.1 pg/mL). Multivariate analysis identified high sCLEC-2 levels (odds ratio per 10 pg/mL:1.25) as an independent predictor of oxygen therapy requirement. sCLEC-2 was positively correlated with cell-free DNA, supporting the association between platelet activation and neutrophil extracellular traps. In conclusion, sCLEC-2 is a clinically valuable marker in predicting oxygen therapy requirements for patients with COVID-19.

What is the context? During the COVID-19 epidemic with tremendous damage to healthcare systems worldwide, predicting the clinical course of patients and allocating limited medical resources appropriately is crucial.Platelets are involved in microthrombosis - a critical pathogenesis of COVID-19. The role of soluble CLEC-2 (sCLEC-2), a novel in vivo platelet activation marker, in predicting the prognosis of COVID-19 remains unexplored.What is new? sCLEC-2 is an independent predictive marker of oxygen therapy requirement in COVID-19.What is the impact? In most cases, patients requiring oxygen therapy must be hospitalized. The ability to predict such cases during the COVID-19 epidemic, when medical recourses are depleted, may contribute to the appropriate allocation of medical resources.

Neurofibroma with adenosis in the mammary gland: a case report.

BACKGROUND: Neurofibroma of the breast is extremely rare, with only a few reported cases. Here, we report a case of solitary neurofibroma of the breast in a 95-year-old woman. CASE PRESENTATION: A 95-year-old woman presented with a palpable mass in the left breast. Mammography revealed a well-defined mass. A 1.6-cm round mass was found in the lower outer quadrant of the left breast on ultrasonography. The internal echo of the tumor was a mixture of relatively uniform hypoechoic areas with posterior enhancement and heterogeneous hyperechoic areas. She underwent a core needle biopsy. The pathological findings revealed a spindle cell lesion with no malignant findings. At 2 months follow-up, repeat breast ultrasonography showed that the mass had enlarged to be 2.7 cm in size. A repeat core needle biopsy, however, revealed no particularly new information. Because the tumor was growing and a definite diagnosis was not made, lumpectomy was performed. We found bland-spindled cells with shredded-carrot collagen bundles. Immunohistochemical antibody markers (S100, SOX10, and CD34) were positive for the spindle cells. Some of the tumors maintained the bilayer nature of luminal cells and myoepithelial cells, which might be the reason for internal heterogeneity on ultrasound. A histological diagnosis of neurofibroma with adenosis was made. At 6 months follow-up, no recurrent lesions were found. CONCLUSIONS: Ultrasound and pathological images revealed an extremely rare case of neurofibroma combined with adenosis. Tumor resection was performed because it was difficult to make a definitive diagnosis using needle biopsy. Even when a benign tumor is suspected, short-term follow-up is necessary, and if an enlargement is observed, early tumor resection is recommended.

Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury.

Drug-induced liver injury (DILI) is one of the major causes for the discontinuation of drug development and withdrawal of drugs from the market. Since it is known that reactive metabolite formation and being substrates or inhibitors of cytochrome P450s (P450s) are associated with DILI, we systematically investigated the association between human P450 inhibition and DILI. The inhibitory activity of 266 DILI-positive drugs (DILI drugs) and 92 DILI-negative drugs (no-DILI drugs), which were selected from Liver Toxicity Knowledge Base (US Food and Drug Administration), against 8 human P450 forms was assessed using recombinant enzymes and luminescent substrates, and the threshold values showing the highest balanced accuracy for DILI discrimination were determined for each P450 enzyme using receiver operating characteristic analyses. The results showed that among the P450s tested, CYP1A1 and CYP1B1 were inhibited by DILI drugs more than no-DILI drugs with a statistical significance. We found that 91% of drugs that showed inhibitory activity greater than the threshold values against CYP1A1 or CYP1B1 were DILI drugs. The results of internal 5-fold cross-validation confirmed the usefulness of CYP1A1 and CYP1B1 inhibition data for the threshold-based discrimination of DILI drugs. Although the contribution of these P450s to drug metabolism in the liver is considered minimal, our present findings suggest that the assessment of CYP1A1 and CYP1B1 inhibition is useful for screening DILI risk of drug candidates at the early stage of drug development.

Duodenal adenocarcinoma successfully diagnosed with transabdominal ultrasonography.

Adenocarcinoma arising from the duodenum is relatively rare. Diagnosis of this disease at an early stage is difficult because its symptoms are usually nonspecific. We herein present a case in which duodenal adenocarcinoma was successfully found by transabdominal ultrasonography. Under ultrasonography, the tumor was located in the proximal duodenum apart from the papilla of Vater, and the serosa was intact. Other diagnostic modalities showed no evidence of adjacent organ invasion or distant metastasis. Therefore, pancreatoduodenectomy was performed and the postoperative course was uneventful. The ultrasonographic findings corresponded well with the pathological diagnosis. The following three procedures were essential in this case: systematic scanning of the digestive tract to determine the location of the lesion, graded compression ultrasound to remove air bubbles from the region of interest, and precise observation of the intestinal walls using proper transducers. The precise and skillful performance of transabdominal ultrasonography using a suitable device can help to diagnose duodenal adenocarcinoma, a rare malignancy.

Measurement of plasma lysophosphatidic acid concentration in healthy subjects: strong correlation with lysophospholipase D activity.

BACKGROUND: Lysophosphatidic acid (LPA) plays important roles in a variety of biological responses, especially in the area of vascular biology, and the determination of its plasma concentration is believed to be important. Several mechanisms are known to be involved in the metabolism of LPA. METHODS: To identify factors that may determine the plasma concentrations of this important bioactive lipid, we examined its concentrations using an enzymatic cycling assay and related parameters in 146 healthy subjects. RESULTS: The LPA concentration was significantly higher in women (mean +/- SD, 0.103 +/- 0.032 micromol/L; n = 47) than in men (0.077 +/- 0.026 micromol/L; n = 99). A multiple regression analysis showed a strong positive correlation between the plasma LPA concentration and serum lysophospholipase D (lysoPLD) activity, while the LPA concentration was correlated with the plasma lysophosphatidylcholine (LPC) concentration only in men. Other lipid-related parameters were only slightly correlated or were not correlated with the LPA concentration. CONCLUSIONS: Our findings suggested that conversion from LPC by lysoPLD might be the major route for LPA production in plasma.