Background: Perforator mapping has been well described in the literature. Once the suprafascial plane is reached, the course of perforators is considered constant. However, the surgeon must be aware of whether an anastomosis exists between perforators superficially to the fascia, in order to choose the best vessel upon which to base the reconstruction. Our retrospective in vivo anatomical study of lower leg perforator flaps presents the first description of variations in the suprafascial path of perforators, which may influence preoperative flap design. Methods: An anatomical study of lower limb perforators was performed on 46 nonconsecutive patients who were referred to our department from June 2012 to October 2018. Reconstruction with perforator-based propeller flaps was planned for each of the patients. In total, 72 perforators were preoperatively identified and surgically isolated. The suprafascial course of each perforator was reported. Results: During suprafascial surgical exploration, branching patterns were observed in four perforators. These perforators had been classified as single vessels in the preoperative ultrasonographic analysis. However, after surgical dissection, distal converging branches were noted in two of them. Conclusions Our study is the first description in the literature of suprafascial converging perforators, which might constitute an obstacle to planned reconstruction procedures. Despite the accuracy of preoperative evaluations, anatomical variations were present. Knowledge of suprafascial perforator variations may help surgeons to choose the correct perforator upon which to base a planned flap.

Background: Hyperglycemia is associated with impaired bone health in patients with diabetes mellitus. Although a direct detrimental effect of hyperglycemia on the bone has been previously reported, the specific molecular mediator(s) responsible for the inhibitory effect of high glucose levels on the bone remains unclear. We hypothesized that thioredoxin-interacting protein (Txnip), an essential mediator of oxidative stress, is such a mediator. Methods: We cultured MG-63 cells (immortalized human osteoblasts) with normal or high glucose concentrations and transfected them with scrambled or Txnip-specific small interfering RNA (siRNA). Results: High glucose levels increased Txnip expression and reduced MG-63 cell proliferation. The high-glucose level mediated reduction in cell proliferation was prevented in Txnip siRNA-transfected cells. In addition, we demonstrated that silencing Txnip mRNA expression in osteoblasts reduced the expression of the osteocalcin gene. Our results suggest that high glucose levels or silencing of Txnip mRNA expression may induce apoptosis in osteoblasts. Conclusions Our findings indicate that Txnip is an intracellular mediator of the anti-proliferative effects of extracellular high glucose levels on osteoblasts.

Background: Hyperglycemia is associated with impaired bone health in patients with diabetes mellitus. Although a direct detrimental effect of hyperglycemia on the bone has been previously reported, the specific molecular mediator(s) responsible for the inhibitory effect of high glucose levels on the bone remains unclear. We hypothesized that thioredoxin-interacting protein (Txnip), an essential mediator of oxidative stress, is such a mediator. Methods: We cultured MG-63 cells (immortalized human osteoblasts) with normal or high glucose concentrations and transfected them with scrambled or Txnip-specific small interfering RNA (siRNA). Results: High glucose levels increased Txnip expression and reduced MG-63 cell proliferation. The high-glucose level mediated reduction in cell proliferation was prevented in Txnip siRNA-transfected cells. In addition, we demonstrated that silencing Txnip mRNA expression in osteoblasts reduced the expression of the osteocalcin gene. Our results suggest that high glucose levels or silencing of Txnip mRNA expression may induce apoptosis in osteoblasts. Conclusions Our findings indicate that Txnip is an intracellular mediator of the anti-proliferative effects of extracellular high glucose levels on osteoblasts.

Background: Hyperglycemia is associated with impaired bone health in patients with diabetes mellitus. Although a direct detrimental effect of hyperglycemia on the bone has been previously reported, the specific molecular mediator(s) responsible for the inhibitory effect of high glucose levels on the bone remains unclear. We hypothesized that thioredoxin-interacting protein (Txnip), an essential mediator of oxidative stress, is such a mediator. Methods: We cultured MG-63 cells (immortalized human osteoblasts) with normal or high glucose concentrations and transfected them with scrambled or Txnip-specific small interfering RNA (siRNA). Results: High glucose levels increased Txnip expression and reduced MG-63 cell proliferation. The high-glucose level mediated reduction in cell proliferation was prevented in Txnip siRNA-transfected cells. In addition, we demonstrated that silencing Txnip mRNA expression in osteoblasts reduced the expression of the osteocalcin gene. Our results suggest that high glucose levels or silencing of Txnip mRNA expression may induce apoptosis in osteoblasts. Conclusions Our findings indicate that Txnip is an intracellular mediator of the anti-proliferative effects of extracellular high glucose levels on osteoblasts.

Background: Hyperglycemia is associated with impaired bone health in patients with diabetes mellitus. Although a direct detrimental effect of hyperglycemia on the bone has been previously reported, the specific molecular mediator(s) responsible for the inhibitory effect of high glucose levels on the bone remains unclear. We hypothesized that thioredoxin-interacting protein (Txnip), an essential mediator of oxidative stress, is such a mediator. Methods: We cultured MG-63 cells (immortalized human osteoblasts) with normal or high glucose concentrations and transfected them with scrambled or Txnip-specific small interfering RNA (siRNA). Results: High glucose levels increased Txnip expression and reduced MG-63 cell proliferation. The high-glucose level mediated reduction in cell proliferation was prevented in Txnip siRNA-transfected cells. In addition, we demonstrated that silencing Txnip mRNA expression in osteoblasts reduced the expression of the osteocalcin gene. Our results suggest that high glucose levels or silencing of Txnip mRNA expression may induce apoptosis in osteoblasts. Conclusions Our findings indicate that Txnip is an intracellular mediator of the anti-proliferative effects of extracellular high glucose levels on osteoblasts.

Purpose: To explore the role of artificial intelligence and machine learning (ML) techniques in oncological urology. In recent years, our group investigated the prostate cancer gene 3 (PCA3) score, prostate-specific antigen (PSA), and free-PSA predictive role for prostate cancer (PCa), using the classical binary logistic regression (LR) modeling. In this research, we approached the same clinical problem by several different ML algorithms, to evaluate their performances and feasibility in a real-world evidence PCa detection trial. Materials and Methods: The occurrence of a positive biopsy has been studied in a large cohort of 1,246 Italian men undergoing first or repeat biopsy. Seven supervised ML algorithms were selected to build biomarkers-based predictive models: generalized linear model, gradient boosting machine, eXtreme gradient boosting machine (XGBoost), distributed random forest/ extremely randomized forest, multilayer artificial Deep Neural Network, naïve Bayes classifier, and an automatic ML ensemble function. Results: All the ML models showed better performances in terms of area under curve (AUC) and accuracy, when compared to LR model. Among them, an XGBoost model tuned by the autoML function reached the best metrics (AUC, 0.830), well overtaking LR results (AUC, 0.738). In the variable importance ranking coming from this XGBoost model (accuracy, 0.824), the PCA3 score importance was 3-fold and 4-fold larger, when compared to that of free-PSA and PSA, respectively. Conclusions The ML approach proved to be feasible and able to achieve good predictive performances with reproducible results: it may thus be recommended, when applied to PCa prediction based on biomarkers fluctuations.

Purpose: To explore the role of artificial intelligence and machine learning (ML) techniques in oncological urology. In recent years, our group investigated the prostate cancer gene 3 (PCA3) score, prostate-specific antigen (PSA), and free-PSA predictive role for prostate cancer (PCa), using the classical binary logistic regression (LR) modeling. In this research, we approached the same clinical problem by several different ML algorithms, to evaluate their performances and feasibility in a real-world evidence PCa detection trial. Materials and Methods: The occurrence of a positive biopsy has been studied in a large cohort of 1,246 Italian men undergoing first or repeat biopsy. Seven supervised ML algorithms were selected to build biomarkers-based predictive models: generalized linear model, gradient boosting machine, eXtreme gradient boosting machine (XGBoost), distributed random forest/ extremely randomized forest, multilayer artificial Deep Neural Network, naïve Bayes classifier, and an automatic ML ensemble function. Results: All the ML models showed better performances in terms of area under curve (AUC) and accuracy, when compared to LR model. Among them, an XGBoost model tuned by the autoML function reached the best metrics (AUC, 0.830), well overtaking LR results (AUC, 0.738). In the variable importance ranking coming from this XGBoost model (accuracy, 0.824), the PCA3 score importance was 3-fold and 4-fold larger, when compared to that of free-PSA and PSA, respectively. Conclusions The ML approach proved to be feasible and able to achieve good predictive performances with reproducible results: it may thus be recommended, when applied to PCa prediction based on biomarkers fluctuations.

Objective: To evaluate the impact of healthcare reorganization during the severe acute respiratory syndrome coronavirus 2 pandemic on Italian colposcopy clinic activities, focusing on cervical excision procedures, follow-ups for conservative management of low-grade lesions, and follow-ups post cervical excision. Methods: Retrospective study conducted in 14 Italian colposcopy clinics. The number and clinical characteristics of cervical excisions, follow-ups for conservative management of low-grade lesions, and follow-ups after cervical excision were compared between the period March 1, 2019 to February 29, 2020 (pre-pandemic) and March 1, 2020 to February 28, 2021 (pandemic) with a Poisson regression analysis. Results: In the pandemic period, the number of cervical excisions was reduced by 8.8% (95% confidence interval [CI]=−15.6% to −2%; p=0.011). Excisions were less frequently performed in the operating room (−35.1%; 95% CI=−47.6% to −22.6%; p<0.001), the number of patients from spontaneous screening was reduced by −14.0% (95% CI=−23.4% to −4.6%; p=0.003), and the CO2-laser technique was used less frequently (−30%; 95% CI=−45.1% to −15.0%; p<0.001). As compared to the pre-pandemic period, the number of follow-ups for conservative management of low-grade lesions was reduced by −26.7% (95% CI=−39.0% to −14.4%; p<0.001), and the follow-up appointments after cervical excision were reduced by −51.0% (95% CI=−58.1% to −43.9%; p<0.001). Conclusion The most significant impact of the healthcare reorganization during the coronavirus disease 2019 pandemic was on follow-ups after cervical excision. The resumption of disrupted activities should follow a risk-based prioritization, starting from women in follow-up after cervical excision. It is advisable that the trend of performing cervical excision as an outpatient procedure is maintained in the post-pandemic period.

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). Conclusion Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic.