Blood Cell-Bound C4d as a Marker of Complement Activation in Patients With the Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is a chronic and disabling condition characterized by recurrent thrombosis and miscarriages mediated by antibodies against phospholipid-binding proteins (aPL), such as beta2glycoprotein I (β2GPI). Complement is involved in APS animal models and complement deposits have been documented in placenta and thrombotic vessels despite normal serum levels. Analysis of circulating blood cells coated with C4d displays higher sensitivity than the conventional assays that measure soluble native complement components and their unstable activation products in systemic lupus erythematosus (SLE). As C4d-coated blood cell count has been reported to be more sensitive than serum levels of complement components and their activation products in systemic lupus erythematosus (SLE) patients, we decided to evaluate the percentage of C4d positive B lymphocytes (BC4d), erythrocytes (EC4d), and platelets (PC4d) in primary APS patients and asymptomatic aPL positive carriers as marker of complement activation in APS. We assessed by flow cytometry the percentages of BC4d, EC4d, and PC4d in primary APS (PAPS; n. 23), 8 asymptomatic aPL positive carriers, 11 APS-associated SLE (SAPS), 17 aPL positive SLE, 16 aPL negative SLE, 8 aPL negative patients with previous thrombosis, 11 immune thrombocytopenia (ITP) patients, and 26 healthy subjects. In addition, we used an in vitro model to evaluate the ability of a monoclonal anti-β2GPI antibody (MBB2) to bind to normal resting or activated platelets and fix complement. EC4d and PC4d percentages were significantly higher in PAPS and aPL carriers as well as aPL positive SLE and SAPS than in aPL negative controls. The highest values were found in PAPS and in SAPS. The EC4d and PC4d percentages were significantly correlated with serum C3/C4 and anti-β2GPI/anti-cardiolipin IgG. In vitro studies showed that MBB2 bound to activated platelets only and induced C4d deposition. The detection of the activation product C4d on circulating erythrocytes and platelets supports the role of complement activation in APS. Complement may represent a new therapeutic target for better treatment and prevention of disability of APS patients

Impact of High‑Grade Patterns in Early‑Stage Lung Adenocarcinoma: A Multicentric Analysis

Objective The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a signifcantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. Methods We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Diferences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-highgrade and high-grade patterns. Results Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a signifcant better prognosis compared to T1a-b-c with high-grade pattern (p=0.020), but the latter had similar OS compared to T2a (p=0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a signifcantly better DFS compared to those with high-grade patterns (p=0.034), and it was similar to T2a (p=0.839). Multivariable analysis confrms the role of T descriptor according to high-grade pattern both for OS (p=0.024; HR 1.285 95% CI 1.033–1.599) and DFS (p=0.003; HR 1.196, 95% CI 1.054–1.344, respectively). These results were confrmed after the propensity score matching analysis. Conclusions pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors

Pathological and clinical features of multiple cancers and lung adenocarcinoma: a multicentre study

OBJECTIVES: Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes.METHODS: We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups.RESULTS: We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008).CONCLUSIONS: In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern

Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM)

: The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended

Factors limiting the efficiency of DMPPT in PV applications

In this paper, the main factors limiting the efficiency of Distributed Maximum Power Point Tracking (DMPPT) in PV applications are analyzed. It is shown why, in a PV system adopting DMPPT and operating under mismatching conditions, it is not always possible to obtain the working of each PV module in its own MPP

A Pulse Compression procedure for power inductors modeling up to moderate non-linearity

Several studies have proved that the use of Ferrite Core (FC) power inductors operating in moderate saturation allows volume and weight of Switch-Mode Power Supplies (SMPSs) to be reduced. Thus, a reliable analysis of non-linear FC inductors operating in moderate saturation is fundamental for the design of high-power-density SMPSs. This paper suggests the application of a Pulse Compression procedure for the Hammerstein model identification of the inductance versus current characteristic of FC inductors. The proposed approach allows a reliable model of FC inductors to be obtained up to moderate saturation non-linearity. Several simulations in cases of practical interest are presented, with comparisons to an established literature behavioral model and its Taylor and Padé numerical approximations

Pulse Compression for Ferrite Inductors Modeling in Moderate Saturation

A reliable analysis of Ferrite Core (FC) inductors operating with moderate saturation is a fundamental requirement in the design of high-power-density switch-mode power supplies. This paper discusses the application of a Pulse Compression procedure to identify the Hammerstein model of the saturation characteristic of FC inductors. The ability of the modeling approach to obtain a reliable model of non-linear FC inductors is tested through simulations in a case of practical interest, with comparisons to a literature behavioral model and its Taylor and Padé numerical approximations