Development and external validation of new ultrasound-based mathematical models for preoperative prediction of high-risk endometrial cancer

To develop and validate strategies, using new ultrasound-based mathematical models, for the prediction of high-risk endometrial cancer and compare them with strategies using previously developed models or the use of preoperative grading only

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

Transvaginal ultrasound-guided biopsy in patients with suspicious primary advanced tubo-ovarian carcinoma

ObjectiveTo assess the accuracy of pathological diagnosis by transvaginal ultrasound-guided biopsy versus surgery in patients with suspicious primary advanced tubo-ovarian carcinoma. The Feasibility, adequacy, and safety of the procedure were also evaluated. MethodsConsecutive women with pre-operative suspicious primary advanced tubo-ovarian carcinoma presenting between July 2019 and September 2021 were enrolled. Accuracy was calculated including only cases who underwent surgery. Feasibility was defined as the number of cases in which ultrasound-guided biopsy was possible according to tumor characteristics (morphology and site). Adequacy was defined as the number of conclusive diagnoses out of the samples collected. Safety was defined by the number of major complications which were defined as hospitalization, surgery, and/or blood transfusion. ResultsA total of 278 patients were eligible for the study; 158 were enrolled, while 120 were excluded for logistic reasons or patient refusal. Ultrasound-guided biopsy was not feasible in 30 (19%) patients. The samples obtained in the remaining 128 patients were all adequate (100%), and no major complications were noted. A total of 26 (20%) patients started neoadjuvant chemotherapy on the basis of the diagnosis obtained by ultrasound, whereas 102 (80%) patients underwent surgery. Accuracy of ultrasound-guided biopsy versus surgery was 94% (96/102), with six false negative cases at ultrasound (6%). Site (prevesical peritoneum) and size (<8 mm) of the nodules resulted as major predictive factors for ultrasound-guided biopsy failure (false negative). Ultrasound-guided biopsy correctly identified 86 primary invasive tubo-ovarian carcinomas and 10 metastatic tumors. ConclusionUltrasound-guided biopsy is a feasible, safe, and accurate method to provide histological diagnosis in suspicious advanced tubo-ovarian cancer patients

Evaluating the Risk of Inguinal Lymph Node Metastases before Surgery Using the Morphonode Predictive Model: A Prospective Diagnostic Study in Vulvar Cancer Patients

Ultrasound examination is an accurate method in the preoperative evaluation of the inguinofemoral lymph nodes when performed by experienced operators. The purpose of the study was to build a robust, multi-modular model based on machine learning to discriminate between metastatic and non-metastatic inguinal lymph nodes in patients with vulvar cancer. One hundred and twenty-seven women were selected at our center from March 2017 to April 2020, and 237 inguinal regions were analyzed (75 were metastatic and 162 were non-metastatic at histology). Ultrasound was performed before surgery by experienced examiners. Ultrasound features were defined according to previous studies and collected prospectively. Fourteen informative features were used to train and test the machine to obtain a diagnostic model (Morphonode Predictive Model). The following data classifiers were integrated: (I) random forest classifiers (RCF), (II) regression binomial model (RBM), (III) decisional tree (DT), and (IV) similarity profiling (SP). RFC predicted metastatic/non-metastatic lymph nodes with an accuracy of 93.3% and a negative predictive value of 97.1%. DT identified four specific signatures correlated with the risk of metastases and the point risk of each signature was 100%, 81%, 16% and 4%, respectively. The Morphonode Predictive Model could be easily integrated into the clinical routine for preoperative stratification of vulvar cancer patients

Topical antibiotic prophylaxis before intravitreal injections: a pilot study

Purpose: To explore whether topical antibiotic prophylaxis in patients scheduled for intravitreal injections achieves surface sterility in a greater proportion of subjects as compared to povidone-iodine alone. Material and methods: A randomized, triple-blind clinical trial. Population: patients scheduled for intravitreal injections for maculopathy. Inclusion criteria: any sex and race, age 18 years and above. Subjects were randomized into 4 groups: the first group applied chloramphenicol (CHLORAM), the second netilmicin (NETILM), the third a commercial ozonized antiseptic solution (OZONE), and the fourth applied no drops (CONTROL). Outcome variable: percentage of non-sterile conjunctival swabs. Specimens were collected before and after the application of 5% povidone-iodine moments before the injection. Results: Ninety-eight subjects (33.7% females, 64.3% males), mean age: 70.2 ± 9.3 years (54-91). Before povidone-iodine, both the CHLORAM and NETILM group showed a lower percentage of non-sterile swabs (61.1% and 31.3% respectively), as compared to the OZONE (83.3%) and CONTROL (86.5%) groups (p < .04). However, this statistical difference was lost after the application of povidone-iodine for 3 min. Percentage of non-sterile swabs in each group after applying 5% povidone-iodine: CHLORAM 11.1%, NETILM 12.5%, CONTROL 15.4%, OZONE 25.0%. This was not statistically significant (p > .05). Conclusions: Topical antibiotic prophylaxis with chloramphenicol or netilmicin drops decreases the bacterial load on the conjunctiva. However, after the application of povidone-iodine, all groups showed a significant reduction in the percentage of non-sterile swabs, and this value was comparable among all groups. For this reason, authors conclude that povidone-iodine alone is sufficient and prior topical antibiotic prophylaxis is not indicated

Laparoscopic intraoperative ultrasound-guided excision with laparoscopic probe in fertility sparing surgery of borderline ovarian tumor recurrence

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Intraoperative ultrasound assistance for the surgical removal of lost intrauterine device

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GestaTIonal TrophoblAstic NeoplasIa Ultrasound assessMent: TITANIUM study

BACKGROUND: There are limited data on ultrasound morphologic features of gestational trophoblastic neoplasia. A predictive model to determine predictors of response to therapy would be ideal in the management of patients with this rare disease. PRIMARY OBJECTIVES AND STUDY HYPOTHESIS: TITANIUM is a prospective, multicenter, observational study aiming to describe ultrasound features of gestational trophoblastic neoplasia and to investigate the role of ultrasound in identifying patients at high risk of resistance to single-drug therapy. The study hypothesis is that ultrasound could improve the International Federation of Gynecology and Obstetrics (FIGO) scoring system for early identification of patients predisposed to single-drug resistance. TRIAL DESIGN AND MAJOR INCLUSION/EXCLUSION CRITERIA: Patients eligible have a diagnosis of gestational trophoblastic neoplasia according to FIGO or the criteria set by Charing Cross Hospital, London, UK. At diagnosis, patients are classified as low-risk (score 0-6) or high-risk (score >6) according to the FIGO risk scoring system, and a baseline ultrasound scan is performed. Patients receive treatment according to local protocol at each institution. Follow-up ultrasound examinations are performed at 1, 4, 10, 16, and 22 months after start of chemotherapy, and at each scan, serum human chorionic gonadotropin (hCG) level, and chemotherapy treatment, if any, are recorded. PRIMARY ENDPOINTS: Our aims are to define ultrasound features of gestational trophoblastic neoplasia and to develop a predictive model of resistance to single-drug therapy in low-risk patients. SAMPLE SIZE: The sample size was calculated assuming that 70% of patients with gestational trophoblastic neoplasia are at low risk, and estimating the rate of resistance to single-drug therapy in this group to be 40%. Assuming a dropout rate of 10%, we should recruit at least 120 patients. With this sample size, we can attempt to create a mathematical model with three variables (either two ultrasound parameters in addition to the risk score or three ultrasound variables statistically significant at univariate analysis) to predict resistance to single-drug therapy in low-risk patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The accrual started in February 2019. Additional referral centers for gestational trophoblastic disease, with similar ultrasound expertise, are welcome to participate in the study. Enrollment should be completed by December 2021, and analysis will be conducted in December 2023. TRIAL REGISTRATION: The study received the Ethical Committee approval of the Coordinator Center (Rome) in January 2019 (Protocol No. 0004668/19)

Ultrasound features and clinical outcome of patients with malignant ovarian masses diagnosed during pregnancy: experience of a gynecological oncology ultrasound center

OBJECTIVE: The number of women diagnosed with ovarian masses during pregnancy has increased in recent years and the management of these women can be controversial. We aim to describe ultrasound characteristics and clinical outcomes of patients with malignant ovarian masses diagnosed during pregnancy. METHODS: Patients with a histological diagnosis of malignant ovarian mass detected during pregnancy who underwent pre-operative ultrasound by experienced ultrasound examiners between December 2000 and November 2017 were included in this retrospective observational study. Ultrasound characteristics of the masses were described using International Ovarian Tumor Analysis terminology. Patients with ovarian masses but without histopathological reports were excluded. Results are presented as absolute frequency (percentage) for nominal variables and as median (range) for continuous variables. Results A total of 22 patients were included in the analysis. The median age was 32.5 (range 23-42) years and median gestational age at diagnosis was 13.5 (range 4-30) weeks. Eight (36.4%) patients had a serous/endocervical-type borderline tumor, seven (31.8%) patients had a primary epithelial ovarian carcinoma, five (22.8%) patients had a metastatic tumor to the ovary, and two (9%) patients had a mucinous borderline tumor. At ultrasound, mucinous borderline tumors were multilocular (1/2, 50%) or multilocular-solid (1/2, 50%) lesions. Serous/endocervical-type borderline tumors were unilocular-solid (3/8, 37.5%) or multilocular-solid (5/8, 62.5%) masses and all had papillary projections. Most invasive epithelial ovarian cancers were multilocular-solid masses (5/7, 71.4%). All metastatic tumors appeared as solid masses. No patients with borderline tumors had a cesarean section due to disease, whereas most patients with epithelial ovarian carcinomas (4/7, 57.2%) and with ovarian metastases (3/5, 60%) had a cesarean section due to disease. No neonatal complication was reported for patients with borderline tumors or epithelial ovarian carcinomas, whereas two of three newborns of patients with metastatic tumor died of the disease. CONCLUSION: At ultrasound, morphological features of malignant ovarian masses detected during pregnancy are similar to those described in non-pregnant patients. The likelihood of undergoing cesarean section increases with malignant disease in the ovary