The Expression of IL-17, in Chronic Spontaneous Urticaria Is Linked to Semaphorin5A.

Background: Patients with chronic spontaneous urticaria (CSU), an autoimmune disorder, show increased skin expression of IL-17A and can benefit from treatment with the anti-IL-17A biologic secukinumab. The mechanisms that drive IL-17A expression in CSU are currently unknown, but may involve Semaphorin5A (Sema5A). Objective: To explore the expression, role, and effects of Sema5A in CSU and its link to IL-17A. Material and Methods: We investigated patients with CSU and healthy controls for skin expression of expressing peripheral T cells. Results: Sema5A was highly expressed in the skin of CSU patients as compared to healthy control skin. Both CD4+ T cells and mast cells in CSU skin expressed Sema5A, and many of them expressed both Sema5A and IL-17A. Patients with CSU had significantly higher rates of IL-17A-expressing CD4+ T cells as compared to healthy controls. Incubation with Sema5A increased the rates of IL-17A-expressing CD4+ T cells in healthy controls to CSU levels. Conclusion: Sema5A may drive the expression and effects of IL-17A in CSU. Further studies in larger cohorts are needed to confirm the role of Sema5A in the pathogenesis of CSU and to explore its potential as a therapeutic target.

The additive value of mpMRI on prostate cancer detection: Comparison between patients with and without a suspicious digital rectal examination (DRE).

PURPOSE: Diagnosis of prostate cancer (CaP) is based on digital rectal examination (DRE) and/or elevated prostate specific antigen (PSA) level. This approach lacks sensitivity and specificity and is associated with many negative biopsies, high rate of diagnosing clinically insignificant disease and lacks accuracy to predict clinically significant (CS) cancer. The addition of multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy reduces the detection of low-grade tumors while improving the detection of CS CaP. Most studies that evaluated mpMRI performance did not separate the DRE status of the examined patients. Therefore, the aim of our study is to investigate whether mpMRI provides similar advantages in detection of CaP according to the DRE findings. MATERIALS AND METHODS: This prospective study included patients with clinically suspected CaP that were referred to MRI-fusion biopsy from 2014 to 2019. All patients had mpMRI of the prostate with an index lesion of PIRADS ≥3. Analysis was done comparing systemic and targeted biopsy. Patients were divided into two groups according to the DRE findings (positive or negative DRE) and the primary outcomes were compared between the 2 study groups: detection rate of CaP and the detection rate of CS disease defined as Gleason score ≥ 7. RESULTS: The final study cohort included 86 patients: 47 with negative DRE and 39 with positive DRE. Overall cancer detection rate was higher in patients with a positive DRE (70.3% vs 48.9%, P <0.05). In the region of interest a higher overall detection rate and of CS disease was found in those with abnormal DRE (51.3% vs. 40.4% and 48.6% vs. 34.0% respectively). The systematic biopsy analysis showed an overall lower detection rate in the negative DRE group (8.5% vs. 18.9 %). The targeted biopsies detected more cancer and significant tumors per core in patients with positive DRE (29.2% vs. 18.5% and 22.1% vs. 14.5% respectively). CONCLUSIONS: Patients submitted to fusion biopsy and have a positive DRE are diagnosed more often with CaP, have higher grade disease and larger tumors. In patients suspicious for CaP and having a significant lesion on mpMRI one should combine targeted and systematic biopsy regardless of the DRE status.