Optimizing complement-activating antibody-based cancer immunotherapy: a feasible strategy?

Passive immunotherapy with monoclonal antibodies (mAb) targeted to specific tumor-associated antigens is amongst the most rapidly expanding approaches to biological therapy of cancer. However, until now a limited number of therapeutic mAb has demonstrated clinical efficacy in selected neoplasia. Results emerging from basic research point to a deeper characterization of specific biological features of neoplastic cells as crucial to optimize the clinical potential of therapeutic mAb, and to identify cancer patients who represent the best candidates to antibody-based immunotherapy. Focus on the tissue distribution and on the functional role of membrane complement-regulatory proteins such as Protectin (CD59), which under physiologic conditions protects tissues from Complement (C)-damage, might help to optimize the efficacy of immunotherapeutic strategies based on C-activating mAb

A Multiphysics Co-Simulation Framework of a Gas Engine and Three-Way Catalyst toward a Complete Vehicle Design Model

In view of the increasingly stringent emission regulations, the automotive sector needs considerable support from the development of robust and reliable engine and aftertreatment models. Accurate reproduction of engine-out and tailpipe pollutants plays a crucial role in complying with these legislations. Given the difficulty in characterizing some critical phenomena, frequently caused by strong dynamics and related to experimental uncertainties, communication between several calibrated and reliable models is mandatory. This is certainly valid for powertrains that will be powered with alternative gas fuels such as natural gas, bio-methane and hydrogen in the future. This paper describes a methodology to co-simulate a 1D CNG HD 6-cyl engine model and a 1D quasi-steady three-way catalyst model in a global framework for high-fidelity virtual prototyping of the vehicle system. Through the implementation of a dedicated control logic in MATLAB/Simulink, the modeling architecture allows for the reproduction of the engine performance parameters together with the evaluation of the TWC pollutants’ conversion efficiency. An extensive database of experimental tests was used to assess the model response. The latter was validated in multiple steady-state operating conditions of the engine workplan. Using a semi-predictive combustion model, the validation was carried out over a wide range of different air-to-fuel ratios and during fast rich/lean transitions to evaluate the formation and conversion phenomena of the main chemical species, both engine-out and tailpipe. Subsequently, the complete model was validated in dynamic conditions throughout a WHTC, accurately reproducing the cut-off phases and their sudden accelerations. The numerical–experimental agreement on pollutant reproduction is generally good and globally below 3%. Larger deviations occur in extremely rich conditions and in CH4 emission evaluation due to the lack of information related to the combustion process and chemical mechanisms involving the Pd surface

Capecitabine plus temozolomide in well- or moderately-differentiated primary atypical neuroendocrine tumours — single-centre experience of two cases

Introduction: Neuroendocrine neoplasms (NENs) are a rare and heterogeneous group of tumours, with a variety of primary origins and variable aggressiveness. NENs with an atypical primary origin, such as breast and retroperitoneal NENs, are extremely rare. As a consequence, an established diagnostic and therapeutic strategy in this particular subgroup is lacking. The combination of capecitabine and temozolomide, called CAPTEM regimen, has produced promising response rates in patients with grade 1 or 2 neuroendocrine tumours of multiple origins. Case presentation: The first is a case of a 68-year-old woman with a metastatic primary breast neuroendocrine tumour, treated with cisplatin plus etoposide as first line, followed by CAV scheme (cyclophosphamide, doxorubicin, and vincristine), and subsequently treated, in third line with the CAPTEM regimen, obtaining radiological response and good tolerance. The second is the case of a 66-year-old woman affected by a metastatic primitive retroperitoneal NET G2. The patient progressed after a somatostatin analogue-based first line, whereas the CAPTEM regimen led to a partial and durable response with a favourable safety profile. Conclusions: CAPTEM chemotherapy has been shown to be an active and safe therapeutic option in advanced, metastatic G1/2 atypical primary NENs

Progetto ARGA (Allergopatie Respiratorie: studio di monitoraggio delle linee guida GINA e ARIA): studio osservazionale tra i Medici di Medicina Generale del territorio nazionale.

non presenteBackground: le linee guida (LG) internazionali GINA (Global Initiative for Asthma) ed ARIA (Allergic Rhinitis and its Impact on Asthma) per la gestione dell\u27asma e RA non sono sufficientemente applicate nella pratica clinica. Obiettivi: valutare il grado di applicabilit? delle LG ed il loro impatto sulla qualit? della vita del paziente in Medicina Generale. Metodi: studio osservazionale prospettico; 168 Medici di Medicina Generale (MMG) (71 del gruppo A (+ corso sulle LG) e 97 del gruppo B (- corso)) sono stati selezionati per arruolare i pazienti con diagnosi di asma/RA. Sia il MMG sia il paziente hanno compilato il questionario sulle Allergopatie Respiratorie e la scheda per la rilevazione delle Reazioni Avverse da Farmaci. Il follow-up verr? eseguito dopo 12 mesi

Lipoprotein(a) levels and risk of adverse events after myocardial infarction in patients with and without diabetes

Introduction: The aim of this study was to evaluate the association of lipoprotein(a) [Lp(a)] levels with long-term outcome in patients with recent history of myocardial infarction (MI), and to investigate if diabetes may influence this association. Methods: Consecutive MI patients who underwent urgent/emergent coronary angiography from February 2013 to June 2019 were prospectively collected. The primary outcome was the composite of MI recurrence and all-cause death. The propensity score weighting technique was used to account for covariates potentially influencing the relationship between Lp(a) levels and the study outcomes. Results: The study population consisted of 1018 post-MI patients (median age 63 years). Diabetes was reported in 280 patients (27.5%), who showed lower Lp(a) levels than patients without diabetes (p = 0.026). At a median follow-up of 1121 days, the primary outcome was reported in 182 patients (17.9%). At univariable Cox regression analysis, Lp(a) was associated with the risk of the primary outcome in the overall population and in non-diabetic patients, but not in diabetics. The adjusted Cox regression analysis confirmed the independent association between Lp(a) values and the primary outcome in non-diabetic patients, but not in diabetics. Lp(a) levels > 70 mg/dL were independently associated with the risk of the primary outcome in non-diabetic patients (adjusted HR: 2.839; 95% CI, 1.382-5.832), but not in diabetics. Conclusions: In this real-world post-MI population, increasing Lp(a) levels were significantly associated with the risk of recurrent MI and all-cause death, and very high Lp(a) serum concentration independently predicted long-term outcome in non-diabetic patients, but not in diabetics

SARS-CoV-2 infection in cancer patients on active therapy after the booster dose of mRNA vaccines

The protective role against SARS-CoV-2 infection by the third booster dose of mRNA vaccines in cancer patients with solid malignancies is presently un- known. We prospectively investigated the occurrence of COVID-19 in cancer patients on active therapy after the booster vaccine dose. Methods: Cancer patients on treatment at the Center for Immuno-Oncology (CIO) of the University Hospital of Siena, Italy, and health care workers at CIO who had received a booster third dose of mRNA vaccine entered a systematic follow-up monitoring period to prospectively assess their potential risk of SARS-CoV-2 infection. Serological and microneu- tralization assay were utilized to assess levels of anti-spike IgG, and of neutralizing antibodies to the SARS-CoV-2 Wild Type, Delta and Omicron variants, respectively, after the booster dose and after negativization of the nasopharyngeal swab for those who had developed COV- ID-19. Results: Ninety cancer patients with solid tumors on active treatment (Cohort 1) and 30 health care workers (Cohort 2) underwent a booster third dose of mRNA vaccine. After the booster dose, the median value of anti-spike IgG was higher (p Z 0.009) in patients than in healthy subjects. Remarkably, 11/90 (12%) patients and 11/30 (37%) healthy subjects tested positive to SARS-CoV-2 infection during the monitoring period. Similar levels of anti-spike IgG and of neutralizing antibodies against all the investigated variants, with geometric mean titers of neutralizing antibodies against the Omicron being the lowest were detected after the booster dose and after COVID-19 in both Cohorts. Conclusions: The occurrence of SARS-CoV-2 infection we observed in a sizable proportion of booster-dosed cancer patients and in healthy subjects during the Omicron outbreak indicates that highly specific vaccines against SARS-CoV-2 variants are urgently required