Multivariate L\'evy Models: Calibration and Pricing

The goal of this paper is to investigate how the marginal and dependence structures of a variety of multivariate L\'evy models affect calibration and pricing. To this aim, we study the approaches of Luciano and Semeraro (2010) and Ballotta and Bonfiglioli (2016) to construct multivariate processes. We explore several calibration methods that can be used to fine-tune the models, and that deal with the observed trade-off between marginal and correlation fit. We carry out a thorough empirical analysis to evaluate the ability of the models to fit market data, price exotic derivatives, and embed a rich dependence structure. By merging theoretical aspects with the results of the empirical test, we provide tools to make suitable decisions about the models and calibration techniques to employ in a real context

Inflammation and Macular Oedema after Pars Plana Vitrectomy

Cystoid macular oedema (CMO) is a major cause of reduced vision following intraocular surgery. Although the aetiology of CMO is not completely clarified, intraocular inflammation is known to play a major role in its development. The macula may develop cytotoxic oedema when the primary lesion and fluid accumulation occur in the parenchymatous cells (intracellular oedema) or vasogenic oedema when the primary defect occurs in the blood-retinal barrier and leads to extracellular fluid accumulation (extracellular oedema). We report on the mechanisms of CMO formation after pars plana vitrectomy and associated surgical procedures and discuss possible therapeutic approaches

Plasminogen activator-coated nanobubbles targeting cell-bound β2-glycoprotein I as a novel thrombus-specific thrombolytic strategy

Beta2-glycoprotein I (β2-GPI) is a serum protein widely recognized as the main target of antibodies present in patients with anti-phospholipid syndrome (APS). β2-GPI binds to activated endothelial cells, platelets and leukocytes, key players in thrombus formation. We developed a new targeted thrombolytic agent consisting of nanobubbles (NBs) coated with recombinant tissue plasminogen activator (rtPA) and recombinant antibody specific for cell-bound β2-GPI. The therapeutic efficacy of targeted nanobubbles was evaluated in vitro, using platelet-rich blood clots, and in vivo in three different animal models: 1) thrombosis developed in a rat model of APS; 2) ferric chloride-induced mesenteric thrombosis in rats, and 3) thrombotic microangiopathy in a mouse model of atypical hemolytic uremic syndrome (C3-gain-of-function mice). Targeted nanobubbles bound preferentially to platelets and leukocytes within thrombi and to endothelial cells through β2-GPI expressed on activated cells. In vitro, rtPA-targeted NBs (rtPA-tNBs) induced greater lysis of platelet-rich blood clots than untargeted NBs. In a rat model of APS, administration of rtPA-tNBs caused rapid dissolution of thrombi and, unlike soluble rtPA that induced transient thrombolysis, prevented new thrombus formation. In a rat model of ferric chloride triggered thrombosis, rtPA-tNBs, but not untargeted NBs and free rtPA, induced rapid and persistent recanalization of occluded vessels. Finally, treatment of C3-gain-of-function mice with rtPA-tNBs, that target β2-GPI deposited in kidney glomeruli, decreased fibrin deposition, and improved urinalysis data with a greater efficiency than untargeted NBs. Our findings suggest that targeting cell-bound β2-GPI may represent an efficient and thrombus-specific thrombolytic strategy in both APS-related and APSunrelated thrombotic conditions

Microwave Ablation in Intermediate Hepatocellular Carcinoma in Cirrhosis: An Italian Multicenter Prospective Study

Background and Aims: To report long-term results in treatment of intermediate hepatocellular carcinoma (HCC) in cirrhotics using new high-powered microwaves (MWS) ablation alone. Methods: This multicenter study included 215 cirrhotics (age range: 67-84 years; 137 males; 149 Child A, 66 Child B) who underwent percutaneous ultrasound-guided high-powered MWS ablation instead of transarterial chemoembolization. Among the patient population, 109 had a single nodule (Ø 5.3-8 cm) [group A], 70 had 2 nodules (Ø 3-6 cm) [group B] and 36 had 3-5 nodules (Ø 1.5-6.8 cm) [group C]. MWS ablation efficacy was evaluated using enhanced-computed tomography and/or magnetic resonance imaging. Primary end-point was 5-year cumulative overall survival (OS). Results: On enhanced-computed tomography and/or magnetic resonance imaging, complete ablation rates were 100% for 1.5-3.5 cm nodules. In nodules >3.5-5 cm, it was 89% for the first ablation and 100% for the second. For lesions >5-8 cm, ablation was up to 92%. Overall, 1-, 3- and 5-year survival rates were 89, 60, and 21%, respectively. The cumulative OS rate of group A was 89%, 66% and 34% at 1, 3 and 5 years. The cumulative OS rate of group B was 88%, 60% and 11% at 1, 3 and 5 years. The cumulative OS rate of group C was 86%, 55% and 0%. The 5-year survival rate was significantly different among the groups (p <0.001). One patient died from rupture of HCC. Upon multivariate analysis, preablation total bilirubin >1.5 mg/dL was an independent factor for predicting lower survival. Conclusions: Percutaneous MWS ablation of intermediate HCC is safe and effective in inducing large volume of necrosis in intermediate HCC nodules, providing long-term survival rates similar to transarterial chemoembolization. Preablation total bilirubin >1.5 mg/dL as expression of liver function reserve is the main factor predicting a worse outcome

The influence of body image on psychological symptomatology in breast cancer women undergoing intervention: a pre-post study

IntroductionBody image concerns related to breast cancer surgery may challenge patients’ quality of life and their treatment outcomes, thus representing a key aspect to be assessed in the psycho-oncological settings. The present longitudinal study is aimed to (1) investigate the association between preoperative body image and postoperative psychological symptoms in breast cancer patients; (2) explore the impact of pre−/post-surgery variation in body image on psychological symptomatology.MethodsN = 72 women undergoing breast cancer surgery were preoperatively screened (T1) using the Body Uneasiness Test (BUT) and were assessed postoperatively (T2) using the Symptom Checklist-90 Revised (SCL-90-R) and re-administered the BUT. Spearman’s correlation was used to investigate the relationship between age, preoperative body image and postoperative psychological symptoms, and variation in body image. To predict post-surgical psychological symptomatology, two separated multiple regression models were used to evaluate preoperative body image and its variation after surgery controlling for covariates (i.e., education; intervention type). P significance was set as 0.05 for all analyses and adjusted for multiple comparisons.ResultsAt T1, anxiety in relation to body image scores emerged as the most frequently experienced psychological symptomatology after surgery (all adjusted p < 0.05). Significant correlations were observed between all SCL-90-R scores at T2 and avoidance behaviors and depersonalization scores at T1. The associations were most significantly strong for somatization, depression, anxiety, and hostility (all adjusted p < 0.05). However, change in body image between pre- and post-intervention was not associated with psychological symptomatology at T2 (all adjusted p > 0.05). Pre-surgery body avoidance was significantly associated with post-intervention psychological symptoms (SOMβ = 0.453, p = 0.0001; DEPβ = 0.507, p = 0.0001; AXβ = 0.459, p = 0.0001; HOSβ = 0.410, p=. 0001). However, increased weight phobia between pre- and post-surgery was statistically associated with increased somatization, anxiety, depression and hostility at T2 (βSOM = 0.439, p = 0.0001; βDEP = 0.454, p = 0.0001; βANX = 0.471, p = 0.0001).DiscussionOverall, pre−/post-intervention body concerns were significantly associated with primary psychological symptoms in breast cancer patients undergoing surgery. Higher levels of body avoidance and weight phobia were significantly associated with the primary psychological dimensions assessed. As body concerns might act as quality-of-life predictors, their evaluation is crucial in fostering patients’ well-being and treatment adherence

Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages: Biliary tree stem cell niche

Stem/progenitors have been identified intrahepatically in the canals of Hering and extrahepatically in glands of the biliary tree. Glands of the biliary tree (peribiliary glands) are tubulo-alveolar glands with mucinous and serous acini, located deep within intrahepatic and extrahepatic bile ducts. We have shown that biliary tree stem/progenitors (BTSCs) are multipotent, giving rise in vitro and in vivo to hepatocytes, cholangiocytes or pancreatic islets. Cells with the phenotype of BTSCs are located at the bottom of the peribiliary glands near the fibromuscular layer. They are phenotypically heterogeneous, expressing transcription factors as well as surface and cytoplasmic markers for stem/progenitors of liver (e.g. SOX9/17), pancreas (e.g. PDX1) and endoderm (e.g. SOX17, EpCAM, NCAM, CXCR4, Lgr5, OCT4) but not for mature markers (e.g. albumin, secretin receptor or insulin). Subpopulations co-expressing liver and pancreatic markers (e.g. PDX1+/SOX17+) are EpCAM+/−, and are assumed to be the most primitive of the BTSC subpopulations. Their descendants undergo a maturational lineage process from the interior to the surface of ducts and vary in the mature cells generated: pancreatic cells in hepatopancreatic ducts, liver cells in large intrahepatic bile ducts, and bile duct cells along most of the biliary tree. We hypothesize that there is ongoing organogenesis throughout life, with BTSCs giving rise to hepatic stem cells in the canals of Hering and to committed progenitors within the pancreas. The BTSCs are likely to be central to normal tissue turnover and injury repair and to be key elements in the pathophysiology of liver, pancreas and biliary tree diseases, including oncogenesis

Transplantation of human fetal biliary tree stem/progenitor cells into two patients with advanced liver cirrhosis.

Efforts to identify cell sources and approaches for cell therapy of liver diseases are ongoing, taking into consideration the limits recognized for adult liver tissue and for other forms of stem cells. In the present study, we described the first procedure of via hepatic artery transplantation of human fetal biliary tree stem cells in patients with advanced cirrhosis.MethodsThe cells were immune-sorted from human fetal biliary tree by protocols in accordance with current good manufacturing practice (cGMP) and extensively characterized. Two patients with advanced cirrhosis (Child-Pugh C) have been submitted to the procedure and observed through a 12 months follow-up.ResultsThe resulting procedure was found absolutely safe. Immuno-suppressants were not required, and the patients did not display any adverse effects correlated with cell transplantation or suggestive of immunological complications. From a clinical point of view, both patients showed biochemical and clinical improvement during the 6 month follow-up (Table1), and the second patient maintained a stable improvement for 12 months.ConclusionThis report represents proof of the concept that the human fetal biliary tree stem cells are a suitable and large source for cell therapy of liver cirrhosis. The isolation procedure can be carried out under cGMP conditions and, finally, the infusion procedure is easy and safe for the patients. This represents the basis for forthcoming controlled clinical trials

Platelet size for distinguishing between inherited thrombocytopenias and immune thrombocytopenia: a multicentric, real life study.

The most frequent forms of inherited thrombocytopenia (IT) are characterized by platelet size abnormalities and it has been suggested that this parameter is useful for their differentiation from immune thrombocytopenia (ITP). Recently, a monocentric study identified cut-off values for mean platelet volume (MPV) and mean platelet diameter (MPD) with good diagnostic accuracy in this respect. To validate these cut-off values in a different and larger case series of patients, we enrolled 130 subjects with ITP and 113 with IT in six different centres. The platelet count and MPV was each measured by the instrument routinely used in each institution. In some centres, platelet count was also measured by optical microscopy. MPD was evaluated centrally by image analysis of peripheral blood films. The previously identified cut-off value for MPV had 91% specificity in distinguishing ITP from inherited macrothrombocytopenias (mono and biallelic Bernard-Soulier, MYH9-related disease), while its sensitivity was greatly variable depending on the instrument used. With an appropriate instrument, specificity was 83%. The diagnostic accuracy of MPD was lower than that obtained with MPV. We concluded that MPV is a useful parameter for differentiating ITP from IT provided that it is measured by appropriate cell counters

Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study

Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures