Updated fractal assessment of Italian Covid-19 disease.

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Vaginal Microbiota and Cytokine Microenvironment in HPV Clearance/Persistence in Women Surgically Treated for Cervical Intraepithelial Neoplasia: An Observational Prospective Study.

High-risk human papillomaviruses (hrHPVs) are causally related to cervical intraepithelial neoplasia (CIN) and subsequent cervical cancer (CC). The vaginal microbiome has been suggested to play a role in the development of CC, but the effect of conservative surgical treatment on the microbiome and hrHPV elimination has not been elucidated. In this study, we aimed to characterize the vaginal microbiome and inflammatory chemokine profile in 85 women treated for CIN2-CIN3 lesions, before and after surgical CIN removal. The results showed, as expected, a high prevalence of dysbiotic microbiomes and vaginal pro-inflammatory cytokines in the CIN cohort, correlated with disease severity, at the basal level. By contrast, surgical CIN removal induced significant vaginal microbiome variations, and specific microbiome/cytokine profiles were associated with hrHPV clearance/persistence at 6-month follow-up. hrHPV-cleared patients, in fact, showed a specific increase of L. crispatus and decrease of dysbiosis and inflammatory cytokines compared to hrHPV-persistent patients. These data highlight the crosstalk between HPV and the local microbiome, and suggest that vaginal microbiome modulation might represent a novel approach to modifying the natural history of hrHPV-related CC. Study registration n. ISRCTN34437150 (https://www.isrctn.com/ISRCTN34437150).

Which is the destiny of ulipristal acetate for uterine fibroids? A commentary on the Italian medicines agency (AIFA) pronouncements

The 19 of February 2018 the Italian Medicines Agency (AIFA - Agenzia Italiana del Farmaco) temporary stopped the new administration of Ulipristal Acetate (UPA) for treating uterine leiomyomas symptoms, because liver injury and hepatic failure had been reported in relationship with UPA use. After the European Medicines Agency review of risks of UPA, the 3 of August 2018 the AIFA produced another note, disclosing that a cause-effect relationship between the UPA use and liver injury is not proved and that some patients can be discontinuously treated if surgery is not recommended. However, a close monitoring of hepatic function must be done in Ulipristal users. As Ulipristal has not been prescribed since February 2018 in our center, the rate of surgical operations for uterine leiomyomas significantly doubled. Therefore it will be useful know exactly which restricted indications allow to use UPA for more than 3 months. In this way it could be minimized the risks of liver injury and it could be prevented the rise of surgeries for uterine leiomyomas.

Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship.

Pelvic carcinosarcomas (PCSs) are rare aggressive biphasic tumors that localize in the ovary, fallopian tube, or peritoneum and present frequently as bilateral disease. We undertook a morphological, p53 immunohistochemical and TP53 gene mutational analysis study in a single institution cohort of 16 PCSs in order to investigate the nature of bilateral tumors and to shed light on their origin and pathogenesis. Of the 16 patients, 10 presented with bilateral disease, 6 with a carcinosarcoma in both adnexa, and the remaining cases with a carcinosarcoma in one adnexum and a carcinoma in the opposite. The carcinoma component showed high-grade serous features in 13/16 of cases (81 %). In 10 patients (63 %), a serous tubal intraepithelial carcinoma (STIC) was found, in one case bilateral, making a total of 11 STICs. STIC was found only in cases with a carcinoma component with high-grade serous features. All 10 bilateral tumors and all 11 PCS-associated STICs showed a similar p53 immunostaining pattern. At mutation analysis of the TP53 gene, all five bilateral PCS contained an identical mutation in both localizations. Furthermore, a TP53 mutation was found in 8 of 10 STICs, with an identical mutation in the associated PCS. The finding of similar p53 immunostaining in all bilateral cases and identical TP53 mutations in most PCS-associated STIC provides evidence for a clonal relation between these neoplastic lesions, supporting a metastatic nature of bilateral PCS and suggesting that they have an extraovarian origin in a STIC.