Le cure palliative nel malato internistico: focus sulle malattie croniche in fase avanzata

Prefazione - Il ruolo del palliativista in medicina interna Gino Gobber Il ruolo del medico internista nelle cure palliative Dario Manfellotto Le cure palliative nel malato non-oncologico Italo Penco La cura del malato fragile alla fine della vita Andrea Fontanella La scuola di specializzazione in Medicina e Cure Palliative Gino Gobber; Dario Manfellotto Introduzione Fabio Gilioli Strumenti per identificare la complessità dei bisogni clinici-assistenziali dei malati e delle loro famiglie Filippo Canzani; Claudio Santini Gestione dei sintomi in fase avanzata: dispnea, delirium, rantolo, nausea e vomito, occlusione intestinale Matteo Moroni Gestione dei sintomi in fase avanzata e nel fine vita: dolore Giuseppe Civardi Approccio assistenziale ai sintomi in fase avanzata e nel fine vita Gabriella Bordin; Michela Guarda De-prescrizione, rimodulazione e sospensione diagnostiche e terapeutiche in fase avanzata di malattia Carlo Lorenzo Muzzulini; Michele Berardi; Alessandro Valle Antibioticoterapia nelle cure palliative Matteo Moroni; Filippo Costanzo Emotrasfusioni in cure palliative Filomena Panzone; Raffaella Antonione Terapia anticoagulante in cure palliative Mauro Silingardi; Raffaella Antonione Ventilazione non invasiva in cure palliative Federico Lari; Raffaella Antonione Scelte terapeutiche in medicina interna: come non perdersi nella complessità del fine vita Miriam Cappelli; Mauro Carbone Raccomandazioni conclusiv

Caregiver’s quality of life in advanced cancer: validation of the construct in a real-life setting of early palliative care

IntroductionEarly palliative care (EPC) improves the quality of life (QoL) of advanced cancer patients and their caregivers. The increasingly widespread use of this care model requires the development of measures supporting its interventions. Although the construct of patient's QoL has been extensively investigated and several QoL measures have been further validated, there is a paucity of data concerning the QoL of the caregiver. In 2018, McDonald and colleagues addressed this issue by interviewing 23 primary caregivers of advanced cancer patients who participated in an EPC randomized clinical trial to understand their perspective on the QoL construct. The Authors identified six major dimensions associated with the construct of caregiver's QoL. The present retrospective study aimed to validate these dimensions on a larger sample and in a real-life EPC setting.MethodsPreviously collected reports from 137 primary caregivers of advanced cancer patients on EPC answering questions about their experience with this care model were qualitatively analyzed through a deductive, thematic approach to identify and confirm the six dimensions constituting the construct of interest based on McDonald's and colleagues' results.ResultsThe six dimensions ("living in the patient's world", "burden of illness and caregiving", "assuming the caregiver role", "renegotiating relationships", "confronting mortality", and "maintaining resilience") were consistently found in the reports from primary caregivers in a real-life EPC setting, confirming to be significant themes associated to their QoL.ConclusionA definite and recurrent construct of primary caregiver's QoL as described by McDonald and colleagues was also found in a larger sample and in a real-life EPC setting. Thus it may lay the groundwork for the development of a dedicated questionnaire

Early palliative care for solid and blood cancer patients and caregivers: Quantitative and qualitative results of a long-term experience as a case of value-based medicine

Introduction: Cancer patients and their caregivers have substantial unmet needs, that negatively impact the clinical outcome and quality of life. However, interventions aimed to address such needs are still suboptimal, failing to answer the recent healthcare call for the adoption of value-based models of care. In the case of incurable oncologic and hematologic cancers, a value-based model of care should plan advanced care on patients' needs and include the quality of death as an outcome. The integration of early palliative care into standard oncologic care for patients with advanced cancers represents a recent innovative model of assistance whose benefits for patients and caregivers are now widely recognized. The key elements underlying the reasons behind these benefits are the multidisciplinary collaboration (teamwork), an honest and empathetic communication between the early palliative care team, the patient, and the caregiver (rapport building), and the ability to detect changes in the physical/psychosocial wellbeing of the patient, along the whole disease trajectory (constant monitoring). Methods: This community case study documents the quantitative and qualitative results of a long term clinical and research experience in delivering early palliative care service to address both solid and blood cancer patients' and their primary caregivers' needs. Results: Data showed decreased use of chemotherapy, blood transfusions and referral to intensive care units near the end of life; increased life expectancy; improved symptom burden and mood; increased frequency of goals-of-care and advanced care planning conversations. Hope perception among bereaved caregivers was associated with resilience and realistic expectations raising from honest communication with the early palliative care team and appreciation toward the model. Patients and caregivers perceived the possibility of a good death as realistic and not as an unlikely event as it was for patients and caregivers on standard oncologic care only. Gratitude expressions toward the model and the team were frequently identified in their reports and positively associated with communication and spirituality. Conclusions: These findings are discussed in the context of an updated literature review regarding value-based care and suggest that early palliative care integrated into standard oncology care may be considered as an effective model of value-based care

Stigma of Palliative Care among Patients with Advanced Cancer and Their Caregivers on Early Palliative Care

Simple Summary Early palliative care represents a successful model of care for advanced cancer patients and their caregivers. Yet, early palliative care provision remains confined to the last weeks of life. Among the possible reasons, the stigma associated with the name "palliative care" seems to have a prominent role. The present study aimed to investigate the perception of palliative care that a sample of 78 patients and 110 caregivers had before their referral to the early palliative care service. The results suggest on which levels it is necessary to intervene to overcome the stigma. From a policy perspective, it is clear that broad education is needed to ensure a more widespread understanding of the essence of anticipated palliative care. The early referral to palliative care (PC) represents a successful value-based model with proven benefits regarding the quality of life and clinical outcomes for advanced cancer patients and their caregivers. Yet, its provision remains typically confined to the last weeks of life as per the historical, late PC model. The stigma according to which PC represents end-of-life care has been identified as the root of the problem. To explore the presence and effects of the stigma in a clinical context, we surveyed 78 patients and 110 caregivers (mean age: 71.7 and 60.7, respectively) on early PC to study what their perception of PC was before their direct experience. The responses were analyzed through a qualitative descriptive approach. The participants explicitly mentioned a lack of knowledge about PC (53% of the sample), which they identified also among physicians and the population (13%); an identification of PC with the late PC model (53%); and a detrimental reaction to the proposal of an early PC referral (83%). However, the participants explicitly mentioned that a direct experience of early PC allowed for an acquired awareness of early PC meaning and benefits (52%), as well as a comprehension of its differences with late PC (34%); the regret for the delayed referral (8%); the perception of the word "palliative" as a barrier (21%); and the belief that early PC should be part of the cancer routine practice (25%). A comprehensive multi-level intervention is necessary for a widespread understanding of the essence of anticipated PC

Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia

Nucleophosmin(NPM1)-mutated protein, a leukemia-specific antigen, represents an ideal target for AML immunotherapy. We investigated the dynamics of NPM1-mutated-specific T cells on PB and BM samples, collected from 31 adult NPM1-mutated AML patients throughout the disease course, and stimulated with mixtures of 18 short and long peptides (9-18mers), deriving from the complete C-terminal of the NPM1-mutated protein. Two 9-mer peptides, namely LAVEEVSLR and AVEEVSLRK (13.9-14.9), were identified as the most immunogenic epitopes. IFNγ-producing NPM1-mutated-specific T cells were observed by ELISPOT assay after stimulation with peptides 13.9-14.9 in 43/85 (50.6%) PB and 34/80 (42.5%) BM samples. An inverse correlation between MRD kinetics and anti-leukemic specific T cells was observed. Cytokine Secretion Assays allowed to predominantly and respectively identify Effector Memory and Central Memory T cells among IFNγ-producing and IL2-producing T cells. Moreover, NPM1-mutated-specific CTLs against primary leukemic blasts or PHA-blasts pulsed with different peptide pools could be expanded ex vivo from NPM1-mutated AML patients or primed in healthy donors. We describe the spontaneous appearance and persistence of NPM1-mutated-specific T cells, which may contribute to the maintenance of long-lasting remissions. Future studies are warranted to investigate the potential role of both autologous and allogeneic adoptive immunotherapy in NPM1-mutated AML patients

Identification and validation of diagnostic cut-offs of the ELISpot assay for the diagnosis of invasive aspergillosis in high-risk patients

Objective: We investigated the performance of enzyme linked immunospot (ELISpot) assay for the diagnosis of invasive aspergillosis (IA) in high-risk patients with hematologic malignancies. Methods: We prospectively enrolled two cohorts of patients undergoing intensive myelosuppressive or immunosuppressive treatments at high risk for IA. ELISpot was performed to detect Aspergillus-specific T cells producing Interleukin-10. Results: In the discovery cohort, a derived cut-off of 40 spot forming cells (SFCs)/106 PBMCs has shown to correctly classify IA cases with a sensitivity and specificity of 89.5% and 88.6%, respectively. This cut-off is lowered to 25 SFC when considering the subset of possible IA patients, with sensitivity and specificity of 76% and 93%, respectively. The application of the 40 SFCs cut-off to the validation cohort resulted in a positivity rate of 83.3% in proven/probable cases and a negativity rate of 92.5% in possible/non-IA cases. Adopting the 25 SCFs cut-off, the assay resulted positive in 83.3% of proven/probable cases while it resulted negative in 66.7% of possible/non-IA cases. Conclusions: ELISpot shows promises in the diagnosis of IA and the possibility to use two distinct cut-offs with similar diagnostic performances according to patients' different pre-test probability of infection can widen its use in patients at risk

Prognostic Relevance of Multi-Antigenic Myeloma-Specific T-Cell Assay in Patients with Monoclonal Gammopathies

: Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies

Le risposte della biodiversità edafica alla gestione degli agroecosistemi: un approccio basato sull’Ecologial Network Analysis

La comprensione del ruolo della biodiversità nella genesi, regolazione e rigenerazione dei servizi ecosistemici richiede una adeguata analisi della sua struttura, dei suoi tratti funzionali e dell’interazione tra i tratti funzionali e processi ecosistemici. È inoltre necessario comprendere come questi processi sia influenzati da variabili ambientali abiotiche, dalle pratiche di gestione degli ecosistemi e dalle perturbazioni. Una adeguata conoscenza di questi aspetti può contribuire alla definizione di strategie sostenibili di gestione degli agroecosistemi. L’indagine del legame tra la struttura delle comunità ecologiche, definita in termini di taxa presenti e della loro abbondanza, e i processi ecologici che esse promuovono e regolano richiede adeguati strumenti di modellazione. L’Ecological Network Analysis (ENA) rappresenta una prospettiva metodologica particolarmente interessante. Secondo questo approccio le comunità biotiche sono considerate come reti i cui nodi (componenti della biodiversità, come specifici taxon o gruppi funzionali) sono caratterizzati da attributi (quali, ad esempio, presenza/assenza, abbondanza, grado di attivazione di specifici tratti funzionali) e da specifici modelli di interazione con altri nodi. L’obiettivo di questo studio è l’utilizzo di un approccio basato sull’ENA per indagare come le variabili ambientali e le strategie di gestione influenzano la fauna di artropodi del suolo nell’agroecosistema vigneto. Nel lavoro sono stati considerati due approcci statistici alla valutazione delle relazioni di una rete ecologia: il Gaussian Graphical Model (GGM) e la Bayesian Network (BN). Entrambi i modelli consentono una rappresentazione grafica delle reti investigate, elemento che rende i risultati ottenuti di più facile interpretazione. Il GGM è una rete non diretta basata su coefficienti di correlazione parziale e può essere utilizzata come strumento esplorativo di analisi dei dati. La BN è un modello grafico probabilistico che consente di investigare le dipendenze condizionali tra i nodi della rete. Entrambi i modelli consentono di valutare le relazioni sia con indicazione di presenza/assenza sia di abbondanza dei taxa considerati. Tali modelli sono stati applicati all’analisi della biodiversità degli artropodi edafici in oltre 290 vigneti, situati in diversi areali viticoli prevalentemente nel Nord Italia. Per ogni vigneto si è effettuato un campionamento del suolo a una profondità di circa 0-15 cm. In questi campioni di suolo sono stati identificati i diversi taxa di artropodi e si è definita la loro abbondanza. Per ogni sito sono state indagate le caratteristiche chimico fisiche dei suoli e di definite le modalità di gestione agronomica (conduzione convenzionale o biologica, modalità di gestione dell’inerbimento e di concimazione). Applicando i GGM e le BN a questa importante base dati, abbiamo stimato una serie di reti di biodiversità edafica diversificando i vigneti in base alle tipologie di conduzione, di gestione e alle caratteristiche geo-pedologiche dei siti. I modelli hanno consentito di identificare i taxa “centrali” nella determinazione delle relazioni di presenza e abbondanza degli altri taxa, quali ad esempio acari e isopodi. Lo sviluppo del lavoro prevede di caratterizzare in maniera dettagliata aspetti funzionali dei taxa per interpretare in che modo le relazioni individuate assumano un significato nei termini di relazione ecologiche tra i gruppi e come tali relazioni concorrano a determinare gli aspetti funzionali del suolo nel suo compless

Impact of Environmental Conditions and Management on Soil Arthropod Communities in Vineyard Ecosystems

The importance of soil biodiversity and soil-based ecosystem services in the context of viticulture has recently been emphasized. Over 85% of soil fauna species richness is represented by edaphic arthropod communities. Edaphic arthropod responses to soil characteristics and management practices can be considered as good bioindicators of soil quality. Here, 168 soil samples that were collected from 2014 to 2019 in several vineyards of different Italian wine-growing areas were analyzed to explore how arthropod communities respond to several factors that are characteristic of vineyard ecosystems. The analysis of the combined effects of the primary abiotic variables (the chemical and physical characteristics of soil) and management practices (organic vs. conventional, soil inter-row management) on soil biological quality (assessed by QBS-ar index) identified soil temperature and soil texture as the abiotic factors exerting the most significant effect on the QBS-ar values. Organic vineyards exhibited higher QBS-ar values compared to those of conventionally managed vineyards, and subsoiling negatively influenced the soil biological quality