Inter-rater agreement of CDC criteria and ASEPSIS score in assessing surgical site infections after cesarean section: a prospective observational study.

Objective: To assess and compare the inter-rater agreement of the CDC criteria and the ASEPSIS score in identifying surgical site infections after cesarean section. Methods: Prospective observational study including 110 patients subjected to a cesarean section at our institution. Surgical wounds were managed according to standard care and were photographed on the third, seventh, and thirtieth postoperative day or during any evaluation in case of complications. Three expert surgeons reviewed the prospectively gathered data and photographs and classified each wound using CDC criteria and the ASEPSIS score. The inter-rater agreements of CDC criteria and ASEPSIS score were determined with Krippendorff's Alpha with linear weights and compared with a confidence interval approach. Results: The weighted α coefficient for CDC criteria was 0.587 (95%CI, 0.411-0.763, p < 0.001, "moderate" agreement according to Altman's interpretation of weighted agreement coefficient), while the weighted α coefficient for the ASEPSIS score was 0.856 (95%CI, 0.733-0.980, p < 0.001, "very good" agreement). Conclusion: ASEPSIS score presents a "very good" inter-rater agreement for surgical site infections identification after cesarean, resulting in a more objective method than CDC criteria ("moderate" inter-rater agreement). ASEPSIS score could represent an objective tool for managing and monitoring surgical site infections after cesarean section, also by photographic evaluation.

Hysterectomy for cervical intraepithelial neoplasia: A retrospective observational multi-institutional study.

OBJECTIVE: To analyze the clinical management, the outcomes, and the trend in hysterectomy rates (HR) in patients who underwent this procedure for cervical intraepithelial neoplasia (CIN). METHODS: Multicentric retrospective observational study conducted on 242 patients who underwent hysterectomy for CIN between 2010 and 2020 in nine Italian institutions. Hysterectomy for invasive or micro-invasive neoplasia, sub-total hysterectomy, or trachelectomy were excluded. RESULTS: A significant increase in the trend of HR for CIN was recorded (P = 0.002, r = 0.81; C.I. 95%: 0.415-0.949); HR increased from 0.46% in the year 2010 to 3.32% in 2020. The mortality rate was 0.4%, and 5% had operative complications. On definitive histopathology examination, a CIN of any grade was recorded in 71.5% of cases, and an occult invasive cancer in 1.24%. No pathology or CIN1 was found in 26.8% of cases, suggesting over treatment. During follow-up, a vaginal lesion was recorded in 5% of cases. CONCLUSION: A significant increase in the number of hysterectomies performed for CIN in the last 10 years was recorded. Hysterectomy for CIN can lead to complications, risk of the onset of vaginal lesions, and risk of overtreatment, and remains, in the first instance, an unacceptable treatment, to be proposed only after adequate counseling.

The Impact of 9-Valent HPV Vaccination on Couple Infertility Prevention: A Comprehensive Review.

A comprehensive literature review was performed to determine the relationship between HPV infection and infertility and the eventual role of the 9-valent vaccine for infertility prevention. The search was extended from January 1997 through July 2021. Data collected from selected articles focused on three main topics: statistical associations between HPV prevalence and assisted reproductive technology (ART) outcome, association between HPV and characteristics of semen, and associations between HPV and miscarriage. Articles that identified HPV genotypes were selected for this review to study the possible role of the 9-valent vaccine in infertility prevention. To date, there is no agreement on the implication HPV female infection has on the fertility and miscarriage rate. Although it can be stated that HPV prevalence among couples with infertility undergoing ART treatment is consistent, it does not seem to affect the performance of oocytes. Otherwise, HPV infection affects sperm parameters, in particular spermatozoa motility. When an association can be found, most cases of HR-HPV involved are those included in the 9-valent vaccine. The correlation between HPV male infection both with asthenozoospermia and increased risk of pregnancy loss could recommend the extension of anti-HPV vaccination to adolescent males along with cancer prevention. Despite the fact that the relation between 9-valent HPV genotypes involved in female infection and miscarriage/infertility is not clear, the impact of this virus on health reproduction is evident. Considering this, the importance of HPV vaccination in adolescent females is confirmed. A vaccine efficacy study could be useful to confirm the importance of primary prevention for couple reproductive health.

Malignant Transformation of Postmenopausal Endometriosis: A Systematic Review of the Literature.

Objective: This study aimed to systematically review the existing literature on malignant transformation of postmenopausal endometriosis to provide information about patient characteristics, hormonal replacement therapy (HRT) use, and outcomes over a period of 52 years (1969-2021). Methods: According to PRISMA guidelines, we searched for (endometriosis OR endometriotic) AND (cancer OR malignancy OR malignant transformation) AND (menopause OR menopausal OR postmenopause OR postmenopausal) in Pubmed (all fields) (accessed on 12 February 2021) and Scopus (Title/Abstract/Keywords) (accessed on 12 February 2021) databases. The only filter used was the English language. Relevant articles were obtained in full-text format and screened for additional references. Eligibility/inclusion criteria: studies including full case description of malignant transformation of endometriosis-related lesions in postmenopause. Results: 75 studies, including 90 cases, were retrieved. The mean age was 55.8 ± 8.5 years. Overall, about 65% of women had a positive personal history of endometriosis/adenomyosis, and 64% of women underwent previous hysterectomy ± bilateral salpingo-oophorectomy. Forty-nine of 74 women used HRT (66.2%). Among the women who used HRT, estrogen-only treatment was taken by approximately 75%. Duration of HRT was longer than five years in 63.3% of cases. About 70% of subjects had histology of endometrioid adenocarcinoma or clear cell carcinoma. Follow-up outcome, available for 61 women, showed a survival rate of 78.7%, recurrence of 9.8%, death of 11.5%. The duration of follow-up had a median of 12 months (interquartile range, 6.75-25 months). Interestingly, over the years of case publication there was a significant inverse correlation with previous history of endometriosis (r = -0.28, p = 0.007), HRT use (r = -0.31, p = 0.006), and previous definitive surgery (r = -0.42, p < 0.001). Conclusions: In the malignant transformation of postmenopausal endometriosis, there are some recurrent clinical conditions: previous endometriosis, major definitive surgery before menopause, and estrogen-only HRT for a relatively long time. However, these clinical conditions have shown a drastic decrease over time. This could likely be the consequence of different attitudes and management of gynecologists linked to up-to-date scientific evidence about the use of major surgery in gynecological pathologies. Malignant transformation of postmenopausal endometriosis is a clinical challenge to be explored further.

Emotional Regulation and Depression: A Potential Mediator between Heart and Mind.

A narrative review of the major evidence concerning the relationship between emotional regulation and depression was conducted. The literature demonstrates a mediating role of emotional regulation in the development of depression and physical illness. Literature suggests in fact that the employment of adaptive emotional regulation strategies (e.g., reappraisal) causes a reduction of stress-elicited emotions leading to physical disorders. Conversely, dysfunctional emotional regulation strategies and, in particular, rumination and emotion suppression appear to be influential in the pathogenesis of depression and physiological disease. More specifically, the evidence suggests that depression and rumination affect both cognitive (e.g., impaired ability to process negative information) and neurobiological mechanisms (e.g., hypothalamic pituitary adrenal axis overactivation and higher rates of cortisol production). Understanding the factors that govern the variety of health outcomes that different people experience following exposure to stress has important implications for the development of effective emotion-regulation interventional approaches (e.g., mindfulness-based therapy, emotion-focused therapy, and emotion regulation therapy).

EphA2 induces metastatic growth regulating amoeboid motility and clonogenic potential in prostate carcinoma cells.

EphA2 kinase regulates cell shape, adhesion, and motility and is frequently overexpressed in several cancers, including melanoma, prostate, breast, and colon cancers and lung carcinoma. Although a function in both tumor onset and metastasis has been proposed, the role played by EphA2 in tumor progression is still debated. In melanoma, EphA2 has been reported to affect cell migration and invasiveness allowing cells to move by a proteolysis-independent strategy, commonly referred as amoeboid motility. With the aim to understand the role of EphA2 in prostate cancer metastatic spreading, we stably silenced EphA2 expression in a model of aggressive metastatic prostate carcinoma. Our results show that EphA2 drives the metastatic program of prostate carcinoma, although its involvement greatly differs among metastatic steps. Indeed, EphA2 expression (i) greatly affects prostate carcinoma cell motility style, guiding an amoeboid movement based on Rho-mediated cell rounding and independent from metalloprotases, (ii) is ineffective on transendothelial migration, adhesion onto extracellular matrix proteins, and on resistance to anoikis, (iii) regulates clonogenic potential of prostate carcinoma, thereby increasing anchorage-independent growth and self-renewal, prostasphere formation, tumor onset, dissemination to bone, and growth of metastatic colonies. Our finding indicate that EphA2-overexpressing prostate carcinoma cells gain an invasive benefit from their amoeboid motility style to escape from primary tumors and then, enhancing their clonogenic potential successfully target bone and grow metastases, thereby acknowledging EphA2 as a target for antimetastatic therapy of aggressive prostate cancers.

Tumoral and macrophage uPAR and MMP-9 contribute to the invasiveness of B16 murine melanoma cells.

The aim of this study was to investigate whether tumor cells as well as tumor-associated macrophages (TAMs) contribute to the generation of protease activities essential to tumor cell invasiveness, such as matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9), and the urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR). We found that the enhanced invasiveness through Matrigel-coated filters of B16 murine melanoma cells stimulated with IFNgamma was associated with an higher expression of uPAR and MMP-9 in these cells. Moreover, treatment with anti-MMP-9 or anti-uPAR monoclonal antibodies abrogated the increase of invasiveness in IFNgamma-stimulated melanoma cells, suggesting a cooperation of uPA system and MMP-9 in cytokine-stimulated invasiveness. Invasiveness through Matrigel was also enhanced in B16 melanoma cells exposed to a medium conditioned by TAMs, represented in our experimental model by thioglycollate-elicited macrophages co-cultivated with melanoma cells. Macrophages isolated from these co-cultures were found to express higher levels of uPAR and MMP-9 compared to macrophage cultures alone, and the pro-invasive activity of the co-culture-conditioned medium was abrogated by anti-MMP-9 monoclonal antibodies, but not anti-uPAR monoclonal antibodies. Furthermore, the enhanced uPAR and MMP-9 expression in macrophages co-cultivated with tumor cells seems a rather specific phenomenon, generated through a cell-to-cell contact mechanism. On the whole, our data point to a cooperation between tumor cells and macrophages elicited by tumor cells themselves in generating key enzymes essential in the promotion of tumor invasiveness, such as uPAR and MMP-9.

Arginine metabolism in tumor-associated macrophages in cutaneous malignant melanoma: evidence from human and experimental tumors.

Tumor-associated macrophages (TAMs) may elicit contrasting effects on tumor growth, depending on their biological activities. Macrophages use arginine either to synthesize nitric oxide (NO) through the inducible NO synthase (iNOS) or to produce ornithine through arginase activity. Although the effects of NO are primarily cytotoxic, production of ornithine may promote tumor cell proliferation. Thus, iNOS/arginase balance in TAMs may be crucial in tumor progression. The aim of this study was (a) to explore iNOS and arginase expression in TAMs associated with human melanoma at different stages of tumor progression and (b) to explore whether melanoma cells influence iNOS and/or arginase expression in TAMs under basal condition and in the presence of interferon gamma and/or lipopolysaccharide. Immunohistochemical analyses performed on tissue sections from in situ melanoma, invasive melanoma of different pT categories, and metastatic melanoma revealed that (a) the percentage of iNOS-positive TAMs was significantly higher in in situ and thin melanomas in comparison with more advanced, thicker tumors; (b) the percentage of arginase-positive TAMs did not change among the pT categories analyzed; and (c) the percentage of iNOS-positive TAMs was greater than that of arginase-positive TAMs in peritumoral and intratumoral locations of thin melanomas (pT1). Moreover, by the use of an in vitro experimental protocol represented by B16 murine melanoma cells cocultivated with inflammatory macrophages, we found that melanoma cells stimulate iNOS expression and NO production in macrophages. In conclusion, our in vivo and in vitro results suggest that, mainly in early melanoma lesions, iNOS prevails over arginase in TAMs, a phenomenon possibly stimulated by contact with tumor cells. However, macrophages stimulated by murine melanoma cells secreted a level of NO compatible with an antitumor activity only in the presence of interferon gamma.

Expression of cyclo-oxygenase-2 in macrophages associated with cutaneous melanoma at different stages of progression.

The biological significance of the almost constant presence of macrophages in the tumoral microenvironment is an issue debated by several authors. The major difficulty in understanding the role played by tumor-associated macrophages (TAMs) in tumor progression is due to the contrasting effects of TAMs found in different studies. In addition, there is a limited information on which of the many biological activities expressed by TAMs are critical in inducing stimulatory or inhibitory effect on tumor growth. The aim of our study was: (a) to explore to what extent cyclo-oxygenase-2 (COX-2) in TAMs associated with human melanoma is expressed at different stages of tumor progression; and (b) to explore whether COX-2 expression in TAMs is stimulated by melanoma cells. In order to answer this question, we determined COX-2 positive TAMs associated with cutaneous melanocytic nevi, in situ, invasive and metastatic melanoma. In addition, we investigated whether COX-2 is expressed in peritoneal thioglycollate-elicited macrophages after co-cultivation with murine B16 melanoma cells. We found that COX-2-positive TAMs, as revealed by immunohistochemical analysis, were rare in common nevi and "dysplastic nevi", but present in a high percentage in in situ and thin melanoma. COX-2-positive TAMs were also found in more advanced tumors and metastatic melanoma, although at a significantly lower percentage in these latter. The in vitro protocol revealed that COX-2 was expressed in peritoneal macrophages upon contact with B16 murine melanoma cells, but not with normal murine fibroblasts. On the whole, the results of in vivo and in vitro studies suggest that COX-2 expressed in TAMs appears to act as an effective biomarker of melanoma progression, and melanoma cells themselves might stimulate COX-2 in macrophages.