1,186 research outputs found

    Relaxed area of graphs of piecewise Lipschitz maps in the strict BV-convergence

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    We compute the relaxed Cartesian area in the strict BV-convergence on a class of piecewise Lipschitz maps from the plane to the plane, having jump made of several curves allowed to meet at a finite number of junction points. We show that the domain of this relaxed area is strictly contained in the domain of the classical L1-relaxed area

    Two-Injection Start Regimen of Long-Acting Aripiprazole in 133 Patients With Schizophrenia

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    Purpose/BackgroundBased on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients.Methods/ProceduresWe retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers.Findings/ResultsAdverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects.Implications/ConclusionsThe coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study

    Insights in opiates toxicity: impairment of human vascular mesenchymal stromal cells

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    : The most common pulmonary findings in opiate-related fatalities are congestion and oedema, as well as acute and/or chronic alveolar haemorrhage, the cause of which is thought to be a damage to the capillary endothelium related to ischemia. Human vascular mesenchymal stromal cells (vMSCs) play a fundamental role in tissue regeneration and repair after endothelial cell injury, and they express opioid receptors. The aim of this study was to assess the effect of in vitro morphine exposure on the physiological activity and maintenance of human vMSCs. vMSCs were obtained from abdominal aorta fragments collected during surgery repair and were exposed to incremental doses (0.1 mM, 0.4 mM, 0.8 mM and 1 mM) of morphine sulphate for 7 days. The effect was investigated through cell viability assessment, proliferation assay, reactive oxygen species (ROS) detection assay, senescence-associated β-galactosidase assay, senescent-related markers (p21WAF1/CIP1 and p16INK4) and the apoptosis-related marker caspase 3. Moreover, an ultrastructural analysis by transmission electron microscopy and in vitro vascular differentiation were evaluated. Results showed a decrease of the cellular metabolic activity, a pro-oxidant and pro-senescence effect, an increase in intracellular ROS and the activation of the apoptosis signalling, as well as ultrastructural modifications and impairment of vascular differentiation after morphine treatment of vMSC. Although confirmation studies are required on real fatal opiate intoxications, the approach based on morphological and immunofluorescence methodologies may have a high potential also as a useful tool or as a complementary method in forensic pathology. The application of these techniques in the future may lead to the identification of new markers and morphological parameters useful as complementary investigations for drug-related deaths

    Delta Radiomic Analysis of Mesorectum to Predict Treatment Response and Prognosis in Locally Advanced Rectal Cancer

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    Background: The aim of this study is to evaluate the delta radiomics approach based on mesorectal radiomic features to develop a model for predicting pathological complete response (pCR) and 2-year disease-free survival (2yDFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (nCRT). Methods: Pre- and post-nCRT MRIs of LARC patients treated at a single institution from May 2008 to November 2016 were retrospectively collected. Radiomic features were extracted from the GTV and mesorectum. The Wilcoxon–Mann–Whitney test and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the features in predicting pCR and 2yDFS. Results: Out of 203 LARC patients, a total of 565 variables were evaluated. The best performing pCR prediction model was based on two GTV features with an AUC of 0.80 in the training set and 0.69 in the validation set. The best performing 2yDFS prediction model was based on one GTV and two mesorectal features with an AUC of 0.79 in the training set and 0.70 in the validation set. Conclusions: The results of this study suggest a possible role for delta radiomics based on mesorectal features in the prediction of 2yDFS in patients with LARC

    Insights in opiates toxicity: impairment of human vascular mesenchymal stromal cells

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    : The most common pulmonary findings in opiate-related fatalities are congestion and oedema, as well as acute and/or chronic alveolar haemorrhage, the cause of which is thought to be a damage to the capillary endothelium related to ischemia. Human vascular mesenchymal stromal cells (vMSCs) play a fundamental role in tissue regeneration and repair after endothelial cell injury, and they express opioid receptors. The aim of this study was to assess the effect of in vitro morphine exposure on the physiological activity and maintenance of human vMSCs. vMSCs were obtained from abdominal aorta fragments collected during surgery repair and were exposed to incremental doses (0.1 mM, 0.4 mM, 0.8 mM and 1 mM) of morphine sulphate for 7 days. The effect was investigated through cell viability assessment, proliferation assay, reactive oxygen species (ROS) detection assay, senescence-associated β-galactosidase assay, senescent-related markers (p21WAF1/CIP1 and p16INK4) and the apoptosis-related marker caspase 3. Moreover, an ultrastructural analysis by transmission electron microscopy and in vitro vascular differentiation were evaluated. Results showed a decrease of the cellular metabolic activity, a pro-oxidant and pro-senescence effect, an increase in intracellular ROS and the activation of the apoptosis signalling, as well as ultrastructural modifications and impairment of vascular differentiation after morphine treatment of vMSC. Although confirmation studies are required on real fatal opiate intoxications, the approach based on morphological and immunofluorescence methodologies may have a high potential also as a useful tool or as a complementary method in forensic pathology. The application of these techniques in the future may lead to the identification of new markers and morphological parameters useful as complementary investigations for drug-related deaths

    The relaxed area of S1-valued singular maps in the strict BV-convergence

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    3nononeGiven a bounded open set Ω ⊂ R2, we study the relaxation of the nonparametric area functional in the strict topology in BV (Ω; R2), and compute it for vortex-type maps, and more generally for maps in W1,1(Ω; S1) having a finite number of topological singularities. We also extend the analysis to some specific piecewise constant maps in BV (Ω; S1), including the symmetric triple junction map.Giovanni Bellettini, Simone Carano, Riccardo ScalaBellettini, Giovanni; Carano, Simone; Scala, Riccard

    Preoperative Assessment of Skeletal Muscle Mass and Muscle Quality Using Computed Tomography: Incidence of Sarcopenia in Patients with Intrahepatic Cholangiocarcinoma Selected for Liver Resection

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    Background: Sarcopenia is considered a predictor of poor postoperative and long-term results following liver resection for intrahepatic cholangiocarcinoma (ICC). The aim of our study was to assess the incidence of sarcopenia in patients resected for ICC and its relation to preoperative clinical factors. Methods: Patients resected for ICC in our unit, with available preoperative CT scans within one month before operation, were enrolled in the study. Skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) were assessed for each patient. Results: Thirty patients matched all inclusion criteria. Low SMI values were documented in 15 patients (50.0%), and low SMD values were documented in 10 patients (33.3%). SMI was significantly greater in males (p p = 0.031). In patients who were overweight/obese, the incidence of high SMI was significantly higher than that of low SMI (p = 0.003) and the incidence of low SMD was significantly higher than that of high SMD (p = 0.038). In the univariate analysis, no preoperative factors (clinical and tumor-related factors), in particular BMI, were found to be independent predictors of low SMI. Conclusions: The incidence of sarcopenia was 50.0% in patients selected for liver resection for ICC and was not related to the preoperative clinical factors. A multidisciplinary evaluation of the nutritional status is fundamental before liver resection in patients

    Full automation of total metabolic tumor volume from FDG-PET/CT in DLBCL for baseline risk assessments

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    BACKGROUND: Current radiological assessments of (18)fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging data in diffuse large B-cell lymphoma (DLBCL) can be time consuming, do not yield real-time information regarding disease burden and organ involvement, and hinder the use of FDG-PET to potentially limit the reliance on invasive procedures (e.g. bone marrow biopsy) for risk assessment. METHODS: Our aim is to enable real-time assessment of imaging-based risk factors at a large scale and we propose a fully automatic artificial intelligence (AI)-based tool to rapidly extract FDG-PET imaging metrics in DLBCL. On availability of a scan, in combination with clinical data, our approach generates clinically informative risk scores with minimal resource requirements. Overall, 1268 patients with previously untreated DLBCL from the phase III GOYA trial (NCT01287741) were included in the analysis (training: n = 846; hold-out: n = 422). RESULTS: Our AI-based model comprising imaging and clinical variables yielded a tangible prognostic improvement compared to clinical models without imaging metrics. We observed a risk increase for progression-free survival (PFS) with hazard ratios [HR] of 1.87 (95% CI: 1.31–2.67) vs 1.38 (95% CI: 0.98–1.96) (C-index: 0.59 vs 0.55), and a risk increase for overall survival (OS) (HR: 2.16 (95% CI: 1.37–3.40) vs 1.40 (95% CI: 0.90–2.17); C-index: 0.59 vs 0.55). The combined model defined a high-risk population with 35% and 42% increased odds of a 4-year PFS and OS event, respectively, versus the International Prognostic Index components alone. The method also identified a subpopulation with a 2-year Central Nervous System (CNS)-relapse probability of 17.1%. CONCLUSION: Our tool enables an enhanced risk stratification compared with IPI, and the results indicate that imaging can be used to improve the prediction of central nervous system relapse in DLBCL. These findings support integration of clinically informative AI-generated imaging metrics into clinical workflows to improve identification of high-risk DLBCL patients. TRIAL REGISTRATION: Registered clinicaltrials.gov number: NCT01287741. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40644-022-00476-0

    Full automation of total metabolic tumor volume from FDG-PET/CT in DLBCL for baseline risk assessments

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    Abstract Background Current radiological assessments of 18fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging data in diffuse large B-cell lymphoma (DLBCL) can be time consuming, do not yield real-time information regarding disease burden and organ involvement, and hinder the use of FDG-PET to potentially limit the reliance on invasive procedures (e.g. bone marrow biopsy) for risk assessment. Methods Our aim is to enable real-time assessment of imaging-based risk factors at a large scale and we propose a fully automatic artificial intelligence (AI)-based tool to rapidly extract FDG-PET imaging metrics in DLBCL. On availability of a scan, in combination with clinical data, our approach generates clinically informative risk scores with minimal resource requirements. Overall, 1268 patients with previously untreated DLBCL from the phase III GOYA trial (NCT01287741) were included in the analysis (training: n = 846; hold-out: n = 422). Results Our AI-based model comprising imaging and clinical variables yielded a tangible prognostic improvement compared to clinical models without imaging metrics. We observed a risk increase for progression-free survival (PFS) with hazard ratios [HR] of 1.87 (95% CI: 1.31–2.67) vs 1.38 (95% CI: 0.98–1.96) (C-index: 0.59 vs 0.55), and a risk increase for overall survival (OS) (HR: 2.16 (95% CI: 1.37–3.40) vs 1.40 (95% CI: 0.90–2.17); C-index: 0.59 vs 0.55). The combined model defined a high-risk population with 35% and 42% increased odds of a 4-year PFS and OS event, respectively, versus the International Prognostic Index components alone. The method also identified a subpopulation with a 2-year Central Nervous System (CNS)-relapse probability of 17.1%. Conclusion Our tool enables an enhanced risk stratification compared with IPI, and the results indicate that imaging can be used to improve the prediction of central nervous system relapse in DLBCL. These findings support integration of clinically informative AI-generated imaging metrics into clinical workflows to improve identification of high-risk DLBCL patients. Trial Registration Registered clinicaltrials.gov number: NCT01287741. Graphical Abstrac

    Preoperative Assessment of Skeletal Muscle Mass and Muscle Quality Using Computed Tomography: Incidence of Sarcopenia in Patients with Intrahepatic Cholangiocarcinoma Selected for Liver Resection

    No full text
    Background: Sarcopenia is considered a predictor of poor postoperative and long-term results following liver resection for intrahepatic cholangiocarcinoma (ICC). The aim of our study was to assess the incidence of sarcopenia in patients resected for ICC and its relation to preoperative clinical factors. Methods: Patients resected for ICC in our unit, with available preoperative CT scans within one month before operation, were enrolled in the study. Skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) were assessed for each patient. Results: Thirty patients matched all inclusion criteria. Low SMI values were documented in 15 patients (50.0%), and low SMD values were documented in 10 patients (33.3%). SMI was significantly greater in males (p < 0.001). In patients who were underweight, the incidence of low SMI was significantly higher than that of high SMI (p = 0.031). In patients who were overweight/obese, the incidence of high SMI was significantly higher than that of low SMI (p = 0.003) and the incidence of low SMD was significantly higher than that of high SMD (p = 0.038). In the univariate analysis, no preoperative factors (clinical and tumor-related factors), in particular BMI, were found to be independent predictors of low SMI. Conclusions: The incidence of sarcopenia was 50.0% in patients selected for liver resection for ICC and was not related to the preoperative clinical factors. A multidisciplinary evaluation of the nutritional status is fundamental before liver resection in patients
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