Caregiver preferences and willingness-to-pay for home care services for older people with dementia: A discrete choice experiment in the Milan metropolitan area.

Objectives: Dementia is a major health and social care challenge in high-income countries where most people are cared for in their own homes. This study aimed to elicit caregiver preferences for alternative bundles of home care services in the Milan metropolitan area.

Methods: A binary discrete choice experiment was administered to a sample of informal caregivers of people with dementia recruited through a network of non-profit organizations.

Validation of a PD-1/CD28 chimeric switch receptor to augment CAR-T function in dogs with spontaneous B cell lymphoma.

Chimeric antigen receptor (CAR) T cell therapy has achieved unprecedented clinical outcomes in patients with relapsed/refractory B cell leukemias; however, response rates in patients with large B cell lymphoma (LBCL) are less impressive. Expression of PD-1 on activated T cells and PD-L1 on malignant, stromal, and immune cells within the tumor microenvironment (TME) contribute to CAR-T exhaustion, hypofunction, and treatment failures. Here, a comparative approach is taken to develop a chimeric switch receptor (CSR) with potential to augment CAR-T persistence, function, and clinical efficacy in immune competent, pet dogs with spontaneous B cell lymphoma (BCL).

Applications and Opportunities for Immune Cell CAR Engineering in Comparative Oncology.

Chimeric antigen receptor (CAR) T-adoptive cell therapy has transformed the treatment of human hematologic malignancies. However, its application for the treatment of solid tumors remains challenging. An exciting avenue for advancing this field lies in the use of pet dogs, in which cancers that recapitulate the biology, immunological features, and clinical course of human malignancies arise spontaneously.

Innovative solutions for disease management.

The increasing prevalence of chronic diseases is a driver for emerging big data technologies for healthcare including digital platforms for data collection, systems for active patient engagement and education, therapy specific predictive models, optimized patient pathway models. Powerful bioelectronic medicine tools for data collection, analysis and visualization allow for joint processing of large volumes of heterogeneous data, which in turn can produce new insights about patient outcomes and alternative interpretations of clinical patterns that can lead to implementation of optimized clinical decisions and clinical patient pathway by healthcare professionals.With this perspective, we identify innovative solutions for disease management and evaluate their impact on patients, payers and society, by analyzing their impact in terms of clinical outcomes (effectiveness, safety, and quality of life) and economic outcomes (cost-effectiveness, savings, and productivity).

Unedited allogeneic iNKT cells show extended persistence in MHC-mismatched canine recipients.

Allogeneic invariant natural killer T cells (allo-iNKTs) induce clinical remission in patients with otherwise incurable cancers and COVID-19-related acute respiratory failure. However, their functionality is inconsistent among individuals, and they become rapidly undetectable after infusion, raising concerns over rejection and limited therapeutic potential. We validate a strategy to promote allo-iNKT persistence in dogs, an established large-animal model for novel cellular therapies.

Argumentation and explanation in the law.

This article investigates the conceptual connection between argumentation and explanation in the law and provides a formal account of it. To do so, the methods used are conceptual analysis from legal theory and formal argumentation from AI. The contribution and results are twofold.

Identifying highly active anti-CCR4 CAR T cells for the treatment of T-cell lymphoma.

A challenge when targeting T-cell lymphoma with chimeric antigen receptor (CAR) T-cell therapy is that target antigens are often shared between T cells and tumor cells, resulting in fratricide between CAR T cells and on-target cytotoxicity on normal T cells. CC chemokine receptor 4 (CCR4) is highly expressed in many mature T-cell malignancies, such as adult T-cell leukemia/lymphoma (ATLL) and cutaneous T-cell lymphoma (CTCL), and has a unique expression profile in normal T cells. CCR4 is predominantly expressed by type-2 and type-17 helper T cells (Th2 and Th17) and regulatory T cells (Treg), but it is rarely expressed by other T helper (Th) subsets and CD8+ cells.

Dealing with pluralism: the managerial work of CEOs in Italian public healthcare organizations.

Background: Healthcare organizations are extremely complex. The work of their CEOs is particularly demanding, especially in the public sector, though little is known about how the managerial work of a healthcare organization CEO unfolds. Drawing from scholarship on managerial work and management in pluralistic organizations, we sought to answer the questions: What is the content of managerial work of CEOs in public healthcare in Italy? How do healthcare CEOs perform their managerial work in complex interactions with multiple stakeholders?

Methods: For this study we adopted a multi-method approach in which we conducted a survey to investigate CEO behaviors, tracked CEO working time for 4 weeks, and conducted semi-structured interviews with senior CEOs.

Case Report: Clinical and Serological Hallmarks of Cytokine Release Syndrome in a Canine B Cell Lymphoma Patient Treated With Autologous CAR-T Cells.

Background: Chimeric antigen receptor-T (CAR-T) cells have transformed the treatment of human B cell malignancies. With the advent of CAR-T therapy, specific and in some cases severe toxicities have been documented with cytokine release syndrome (CRS) being the most frequently reported. As dogs develop tumors spontaneously and in an immunocompetent setting, they provide a unique translational opportunity to further investigate the activity and toxicities associated with CAR-T therapy.

Development of a fully canine anti-canine CTLA4 monoclonal antibody for comparative translational research in dogs with spontaneous tumors.

The immune checkpoint inhibitor (ICI) ipilimumab has revolutionized the treatment of patients with different cancer histologies, including melanoma, renal cell carcinoma, and non-small cell lung carcinoma. However, only a subset of patients shows dramatic clinical responses to treatment. Despite intense biomarker discovery efforts linked to clinical trials using CTLA4 checkpoint blockade, no single prognostic correlate has emerged as a valid predictor of outcome.

Genetic re-direction of canine primary T cells for clinical trial use in pet dogs with spontaneous cancer.

Immunocompetent pet dogs develop spontaneous, human-like cancers, representing a parallel patient population for the investigation of chimeric antigen receptor (CAR) therapies. We have optimized a retrovirus-based protocol to efficiently CAR transduce primary T cells from healthy and tumor-bearing dogs. While transduction efficiencies and CAR-T expansion vary among dogs, CAR expression is typically higher and more stable compared with previous protocols, thus enabling human and comparative oncology researchers to use the dog as a pre-clinical model for human CAR-T cell research.

Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting.

Chimeric antigen receptor anti-CD19 (CAR19)-T cell immunotherapy-induced clinical remissions in CD19 B cell lymphomas are often short lived. We tested whether CAR19-engineering of the CD1d-restricted invariant natural killer T (iNKT) cells would result in enhanced anti-lymphoma activity. CAR19-iNKT cells co-operatively activated by CD1d- and CAR19-CD19-dependent interactions are more effective than CAR19-T cells against CD1d-expressing lymphomas in vitro and in vivo.

Building upon the success of CART19: chimeric antigen receptor T cells for hematologic malignancies.

Chimeric antigen receptor T cell (CART) therapy has dramatically changed the therapeutic prospects for B cell malignancies. Over the last decade CD19-redirected CART have demonstrated the ability to induce deep, long-lasting remissions and possibly cure patients with relapsing B cell neoplasms. Such impressive results with CART19 fostered efforts to expand this technology to other incurable malignancies that naturally do not express CD19, such as acute myeloid leukemia (AML), Hodgkin lymphoma (HL) and multiple myeloma (MM).

The prospects and promise of chimeric antigen receptor immunotherapy in multiple myeloma.

Despite encouraging therapeutic advances, multiple myeloma (MM) remains an incurable malignancy. The exciting results of chimaeric antigen receptor (CAR)-based immunotherapy in CD19(+) B-cell malignancies have spurred a great interest in extending the use of the CAR technology to other cancers, including MM. Availability of a specific, tumour-restricted antigen is crucial for the design of successful antibody-based CAR therapy.

Anatomical features and clinical correlations in Caucasian patients with definite arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Aim: Arrhythmogenic right ventrticular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterized by fibrofatty replacement and a high risk of ventricular arrhythmias (VA) and sudden cardiac death (SCD). The aim of the present investigation is to examine the pathological profile and the clinical correlations in a group of ARVD/C patients.

Methods: We conducted a multicenter study evaluating 47 patients (31 men; mean age 37±14 years) with definite ARVD/C.

[Polycitemia vera and pulmonary embolism: case report].

Pulmonary embolism is a rare clinical onset of chronic myeloproliferative diseases. Early diagnosis is very important because medical therapy reduces both mortality and morbility. We describe a case of pulmonary embolism as clinical onset of an unknown myeloproliferative disorder.