Malignancy as a risk factor in single-stage combined approach for simultaneous elective surgical diseases

AbstractObjectiveTo identify morbidity and mortality risk factors in patients with synchronous diseases who underwent single-stage combined (SSC) surgery.MethodsWe considered data of 328 patients, each with multiple, elective, synchronous surgical problems treated by a SSC operation. By univariate and multivariate analysis we evaluated many patient-, disease - or treatment-related variables with respect to post-operative mortality, morbidity, and hospital stay.ResultsTwo combined procedures were synchronously performed in 283 patients (86%), 3 combined procedures in 45 patients (14%). Post-operative mortality and morbidity rates were 3% and 24%, respectively, and median duration of hospital stay was 9 days. The occurrence of a surgical oncology procedure emerged as the most important independent risk factor for post-operative mortality and morbidity.ConclusionsThe safety of SSC surgery for the treatment of synchronous problems appears similar to that of multi-stage procedures. The understanding of risk factors for this surgical approach could be useful in order to improve patient selection

2022-RA-610-ESGO Radiomics and transvaginal ultrasound in adnexal masses: is the next future of diagnostics here?

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Sexual Violence Against Adolescent Girls: Labeling It to Avoid Normalization

Violence against women is a pervasive complex phenomenon that destroys women's feelings of love, trust, and self-esteem. In this commentary, we specifically focus on sexual violence against adolescent girls, whose impact is particularly harmful since it may lead to impaired mental health, social functioning, and neurodevelopment. Between 12% and 25% of adolescent girls throughout the world experience sexual violence, very often perpetrated by a family member or a friend. Moreover, for an alarming proportion of girls, the first sexual experience is coerced. In this article, we review the multiple negative effects of sexual violence against adolescent girls. We also report data derived from our practice in a public Italian referral Centre for Sexual and Domestic Violence (SVSeD) and address the importance of a multidisciplinary clinical approach with adolescent victims of sexual violence

Combinations of ATR, Chk1 and Wee1 Inhibitors with Olaparib Are Active in Olaparib Resistant <i>Brca1</i> Proficient and Deficient Murine Ovarian Cells

Background. Poly(ADP-ribose) polymerases inhibitor (PARPi) have shown clinical efficacy in ovarian carcinoma, especially in those harboring defects in homologous recombination (HR) repair, including BRCA1 and BRCA2 mutated tumors. There is increasing evidence however that PARPi resistance is common and develops through multiple mechanisms. Methods. ID8 F3 (HR proficient) and ID8 Brca1-/- (HR deficient) murine ovarian cells resistant to olaparib, a PARPi, were generated through stepwise drug concentrations in vitro. Both sensitive and resistant cells lines were pharmacologically characterized and the molecular mechanisms underlying olaparib resistance. Results. In ID8, cells with a HR proficient background, olaparib resistance was mainly caused by overexpression of multidrug resistance 1 gene (MDR1), while multiple heterogeneous co-existing mechanisms were found in ID8 Brca1-/- HR-deficient cells resistant to olaparib, including overexpression of MDR1, a decrease in PARP1 protein level and partial reactivation of HR repair. Importantly, combinations of ATR, Chk1 and Wee1 inhibitors with olaparib were synergistic in sensitive and resistant sublines, regardless of the HR cell status. Conclusion. Olaparib-resistant cell lines were generated and displayed multiple mechanisms of resistance, which will be instrumental in selecting new possible therapeutic options for PARPi-resistant ovarian tumors

Combinations of ATR, Chk1 and Wee1 Inhibitors with Olaparib Are Active in Olaparib Resistant Brca1 Proficient and Deficient Murine Ovarian Cells

Background. Poly(ADP-ribose) polymerases inhibitor (PARPi) have shown clinical efficacy in ovarian carcinoma, especially in those harboring defects in homologous recombination (HR) repair, including BRCA1 and BRCA2 mutated tumors. There is increasing evidence however that PARPi resistance is common and develops through multiple mechanisms. Methods. ID8 F3 (HR proficient) and ID8 Brca1-/- (HR deficient) murine ovarian cells resistant to olaparib, a PARPi, were generated through stepwise drug concentrations in vitro. Both sensitive and resistant cells lines were pharmacologically characterized and the molecular mechanisms underlying olaparib resistance. Results. In ID8, cells with a HR proficient background, olaparib resistance was mainly caused by overexpression of multidrug resistance 1 gene (MDR1), while multiple heterogeneous co-existing mechanisms were found in ID8 Brca1-/- HR-deficient cells resistant to olaparib, including overexpression of MDR1, a decrease in PARP1 protein level and partial reactivation of HR repair. Importantly, combinations of ATR, Chk1 and Wee1 inhibitors with olaparib were synergistic in sensitive and resistant sublines, regardless of the HR cell status. Conclusion. Olaparib-resistant cell lines were generated and displayed multiple mechanisms of resistance, which will be instrumental in selecting new possible therapeutic options for PARPi-resistant ovarian tumors

Different Patterns of Platinum Resistance in Ovarian Cancer Cells with Homologous Recombination Proficient and Deficient Background

Platinum compounds are very active in first-line treatments of ovarian carcinoma. In fact, high rates of complete remission are achieved, but most patients eventually relapse with resistant disease. Many mechanisms underlying the platinum-resistant phenotype have been reported. However, there are no data in the same isogenic cell system proficient and deficient in homologous recombination (HR) on platinum-acquired resistance that might unequivocally clarify the most important mechanism associated with resistance. We generated and characterized cisplatin (DDP)-resistant murine ovarian ID8 cell lines in a HR-deficient and -proficient background. Specific upregulation of the NER pathway in the HR-proficient and -resistant cells and partial restoration of HR in Brca1−/−-resistant cells were found. Combinations of different inhibitors of the DNA damage response pathways with cisplatin were strongly active in both resistant and parental cells. The data from the ID8 isogenic system are in line with current experimental and clinical evidence and strongly suggest that platinum resistance develops in different ways depending on the cell DNA repair status (i.e., HR-proficient or HR-deficient), and the upregulation and/or restoration of repair pathways are major determinants of DDP resistance

Machine Learning techniques in breast cancer prognosis prediction: A primary evaluation.

More than 750&nbsp;000 women in Italy are surviving a diagnosis of breast cancer. A large body of literature tells us which characteristics impact the most on their prognosis. However, the prediction of each disease course and then the establishment of a therapeutic plan and follow-up tailored to the patient is still very complicated. In order to address this issue, a multidisciplinary approach has become widely accepted, while the Multigene Signature Panels and the Nottingham Prognostic Index are still discussed options. The current technological resources permit to gather many data for each patient. Machine Learning (ML) allows us to draw on these data, to discover their mutual relations and to esteem the prognosis for the new instances. This study provides a primary evaluation of the application of ML to predict breast cancer prognosis. We analyzed 1021 patients who underwent surgery for breast cancer in our Institute and we included 610 of them. Three outcomes were chosen: cancer recurrence (both loco-regional and systemic) and death from the disease within 32&nbsp;months. We developed two types of ML models for every outcome (Artificial Neural Network and Support Vector Machine). Each ML algorithm was tested in accuracy (=95.29%-96.86%), sensitivity (=0.35-0.64), specificity (=0.97-0.99), and AUC (=0.804-0.916). These models might become an additional resource to evaluate the prognosis of breast cancer patients in our daily clinical practice. Before that, we should increase their sensitivity, according to literature, by considering a wider population sample with a longer period of follow-up. However, specificity, accuracy, minimal additional costs, and reproducibility are already encouraging

The spread of COVID-19 in six western metropolitan regions:a false myth on the excess of mortality in Lombardy and the defense of the city of Milan

We analyzed the spread of the COVID-19 epidemic in 6 metropolitan regions with similar demographic characteristics, daytime commuting population and business activities: the New York metropolitan area, the Île-de-France region, the Greater London county, Bruxelles-Capital, the Community of Madrid and the Lombardy region. The highest mortality rates 30-days after the onset of the epidemic were recorded in New York (81.2 x 100,000) and Madrid (77.1 x 100,000). Lombardy mortality rate is below average (41.4 per 100,000), and it is the only situation in which the capital of the region (Milan) has not been heavily impacted by the epidemic wave. Our study analyzed the role played by containment measures and the positive contribution offered by the hospital care system. (www.actabiomedica.it)