A 15-year experience in pediatric palliative care: a retrospective hospital-based study.

BACKGROUND: The current Italian scenario of pediatric palliative care (PPC) services is characterized by inadequate coverage of the territory. Therefore, it is important to improve the referral of patients to the most appropriate setting (community care, general PPC, or specialized PPC) and to improve the delivery of PPC care. METHODS: Aiming at obtaining information about the referrals to the Padua Pediatric Hospice that could help estimate the investments needed to improve the provision of care, a retrospective analysis has been carried out. The rate of proper referral and discharge, the number of patients followed at the hospice, the mortality rate, and the length of follow-up were analyzed, and, when possible, data were stratified by oncological and non-oncological diseases. RESULTS: The analysis showed that of the 870 patients referred to the Padua Pediatric Hospice between 2008 and 2022, 76% were affected by non-oncological conditions. 82% of patients referred were taken in charge and most of the remaining patients have been inappropriately referred. The analysis showed a growing number of total referrals, which increased by 195% from 2008 to 2022. An increase in proper referrals and referrals of non-oncological patients was observed alongside a decrease in oncological patient referrals and a trend toward a decrease in discharge rates. A decreased mortality was observed in patients with non-oncological conditions, with only 6% of deceased patients in 2022. Moreover, a longer survival with a median follow-up length of 43 months was observed among patients with non-oncological conditions who were followed up at the Padua Pediatric Hospice for more than 12 months. Conversely, the short survival rate observed for oncological patients suggests that those patients should have been referred to PPC earlier to benefit from palliative care for longer periods. CONCLUSIONS: Considering these data, it is expected that the number of patients needing PPC services will steadily increase in the next years. Hence, there is a need to invest resources to provide the best care delivery model encompassing specific pathways for the transition into adulthood, the establishment of networks within all the Italian regions, and an efficient referral to the more suitable setting of care.

Transition to Adulthood in Pediatric Palliative Care: A Narrative Review.

Pediatric palliative care (PPC) is defined as "the active care of the child's body, quality of life, mind and spirit, also giving support to the family". PPC should be established once a diagnosis of life-limiting or life-threatening disease is reached and should continue as long as necessary. Therefore, pediatric palliative care (PPC) can continue for years, also given the improved care approaches for children with life-limiting or life-threatening diseases. Over time, the child may grow to become a young adult, and when this happens, the transition to adult healthcare services must be undertaken. This article discusses possible interventions, fostering an efficient transition from pediatric to adult palliative care. A narrative review presents issues, experiences, and existing programs. A "Perspectives" section presents opinions and proposals by the authors. The transition process is not limited to a change from pediatric to adult services. Rather, it includes the entire process of the development of the child and requires interdisciplinary management with proper planning and collaboration among professionals of pediatric and adult teams.

Emergent quantum phase transition of a Josephson junction coupled to a high-impedance multimode resonator.

The physics of a single Josephson junction coupled to a resistive environment is a long-standing fundamental problem at the center of an intense debate, strongly revived by the advent of superconducting platforms with high-impedance multimode resonators. Here we investigate the emergent criticality of a junction coupled to a multimode resonator when the number of modes is increased. We demonstrate how the multimode environment renormalizes the Josephson and capacitive energies of the junction so that in the thermodynamic limit the charging energy dominates when the impedance is larger than the resistance quantum and is negligible otherwise, independently from the bare ratio between the two energy scales and the compact or extended nature of the phase of the junction. Via exact diagonalization, we find that the transition surprisingly stems from a level anticrossing involving not the ground state, but the first excited state, whose energy gap vanishes in the thermodynamic limit. We clarify the nature of the two phases by pointing at a different behavior of the ground and excited states and we show that at the transition point the spectrum displays universality not only at low frequencies. In agreement with recent experiments, we reveal striking spectral signatures of the phase transition.

Oncological treatment administration at end of life: a retrospective study.

Background: This work evaluated the proportion of patients who continue therapy until their last month of life or initiate a new therapy in the last 3 months of life (end of life [EOL]). Methods: Data for 486 patients were retrospectively collected. Results: In EOL, 205 (42.3%) received systemic therapy. Better performance status (last month overall response [OR]: 0.39; 95% CI: 0.25-0.60; p < 0.001; last 3 months OR: 0.47; 95% CI: 0.34-0.65; p < 0.001) and lack of activation of palliative care (last month OR: 0.26; 95% CI: 0.13-0.54; p < 0.001; last 3 months OR: 0.18; 95% CI: 0.10-0.32; p < 0.001) were associated with higher probability of EOL therapy. Conclusion: A non-negligible proportion of patients in real-life settings continue to receive systemic treatment in EOL.

Unravelling the role of mind-body therapies in paediatric palliative care: A narrative review.

AIM: Given the multifaceted nature of paediatric palliative care (PPC), integrative medicine and mind-body therapies, in particular, are increasingly used in this setting. However, to our knowledge, their use in PPC has never been specifically reviewed. Therefore, this work aims to provide a comprehensive overview of the application and possible beneficial effects of mind-body therapies in the PPC setting. METHODS: Papers about the use of meditation and mindfulness, biofeedback, hypnosis, yoga, tai chi and qi gong, imagery, creative outlets, and art therapy in PPC were identified by browsing PubMed and CINHAL. RESULTS: We found that the harmless nature of mind-body therapies has been extensively described, and available studies consistently show some benefits on the anxiety, stress, and quality of life of parents/caregivers and healthcare providers. However, well-grounded and robust evidence does not fully support the efficacy of mind-body therapies, especially in patients. CONCLUSION: Considering the peculiarity of the PPC setting, we suggest that mind-body therapies should be further considered and properly investigated through larger controlled studies and according to the different populations of PPC children, as well as for parents, caregivers, and healthcare professionals.

Pediatric Palliative Care: Insights into Assessment Tools andReview Instruments.

The proper assessment of needs and outcomes in pediatric palliative care (PPC) is imperativeto ensure the best possible service to patients and families. However, given the multidimensionalnature of PPC, the low number of patients in this setting, the heterogeneity of diseases, the presenceof cognitive impairment in many patients, and the physiological development of children, outcomescan be complex and difficult to measure. Consequently, in this context, the use of standardizedand validated tools to assess the needs of children and families, to assess symptom severity, andto estimate the quality of PPC service represent a current need. Even if efforts have been made tostandardize approaches and tools for palliative care in adults, to our knowledge, a similar comprehensiveassessment of PPC has not yet been conducted to date. This narrative review provides anoverview and discusses the evaluation of tools currently applied in PPC, with an educational intentfor healthcare providers. We found that several instruments are available to assess different dimensionsof PPC. We proposed a classification into eligibility tools, patient and family needs assessmenttools, and care assessment tools. At present, two main eligibility tools exist, the PaPaS Scale and theACCAPED Scale questionnaire. Most of the tools for patient and family needs assessment have notbeen specifically validated in the PPC setting, and many may be more readily applied in researchsettings rather than in daily practice. Similar considerations can be made for tools assessing QoL,while tools assessing PPC service quality seem to be easily applied. Efforts to develop new specifictools and validate existing ones are undoubtedly advocated. However, in the patient's best interest,PPC healthcare providers should start using available tools, regardless of their validation status.

Innovative Nanostructured Fillers for Dental Resins: Nanoporous Alumina and Titania Nanotubes.

The possibility of improving dental restorative materials is investigated through the addition of two different types of fillers to a polymeric resin. These fillers, consisting of porous alumina and TiO2 nanotubes, are compared based on their common physicochemical properties on the nanometric scale. The aim was to characterize and compare the surface morphological properties of composite resins with different types of fillers using analytical techniques. Moreover, ways to optimize the mechanical, surface, and aesthetic properties of reinforced polymer composites are discussed for applications in dental treatments. Filler-reinforced polymer composites are the most widely used materials in curing dental pathologies, although it remains necessary to optimize properties such as mechanical resistance, surface characteristics, and biocompatibility. Anodized porous alumina nanoparticles prepared by electrochemical anodization offer a route to improve mechanical properties and biocompatibility as well as to allow for the controlled release of bioactive molecules that can promote tissue integration and regeneration. The inclusion of TiO2 nanotubes prepared by hydrothermal treatment in the resin matrix promotes the improvement of mechanical and physical properties such as strength, stiffness, and hardness, as well as aesthetic properties such as color stability and translucency. The surface morphological properties of composite resins with anodized porous alumina and TiO2 nanotube fillers were characterized by Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), and X-ray chemical analysis. In addition, the stress-strain behavior of the two composite resins is examined in comparison with enamel and dentin.

Estimating the neutron yield in a deuterium plasma with the JET neutron camera.

The JET neutron camera is a well-established detector system at JET, which has 19 sightlines each equipped with a liquid scintillator. The system measures a 2D profile of the neutron emission from the plasma. A first principle physics method is used to estimate the DD neutron yield that is based on JET neutron camera measurements and is independent of other neutron measurements. This paper details the data reduction techniques, models of the neutron camera, simulations of neutron transport, and detector responses used to this end. The estimate uses a simple parameterized model of the neutron emission profile. The method makes use of the JET neutron camera's upgraded data acquisition system. It also accounts for neutron scattering near the detectors and transmission through the collimator. These components together contribute to 9% of the detected neutron rate above a 0.5 MeVee energy threshold. Despite the simplicity of the neutron emission profile model, the DD neutron yield estimate falls on average within 10% agreement with a corresponding estimate from the JET fission chambers. The method can be improved by considering more advanced neutron emission profiles. It can also be expanded to estimate the DT neutron yield with the same methodology.

A pilot study on sports activities in pediatric palliative care: just do it.

BACKGROUND: There has been a growing interest in studying the value of physical exercise in children with disabilities or chronic health conditions because of evidence of improvement in quality of life, social acceptance, and physical functioning. However, only scant evidence exists for routine sports activities in children requiring pediatric palliative care (PPC), and in most cases, such evidence has been collected in oncological patients. The Pediatric Hospice of Padua is the referral center for PPC in the Veneto region (northern Italy). Starting from the experience of this PPC center, this pilot study aims to describe the personal experience of children and young people who practice physical activity and their caregivers' perspectives, focusing particularly on the emotional and social impact of exercise and sports practice. METHODS: Patients involved in at least one regular and structured sports activity were included in the pilot analysis. Two different ICF-CY (International Classification of Functioning, Disability and Health-Children and Youth Version) scales ("Body Function" and "Activity and Participation") were filled out to assess the children's global functional competence. Two online ad hoc questionnaires were created and administered to children, when able to respond, and caregivers. RESULTS: A total of 9% of patients reported being involved in a sports activity. All children who played sports did not have indications of cognitive retardation. The most practiced sport was swimming. The use of standardized methods such as ICF-CY shown that severe motor impairments do not limit sports accessibility. Questionnaires result suggest that sports are a positive experience for both children needing PPC and their parents. Children encourage other children to do sports and can find the positive side even in difficulties. CONCLUSION: Since PPC is encouraged as early as the diagnosis of incurable pathologies, the inclusion of sports activities in the context of a PPC plan should be considered from the perspective of improving quality of life.

A form to report pain assessment and monitoring in the oncology clinical record: a Delphi process.

Background: Treatment of cancer pain remains suboptimal worldwide. In Italy, a law requires that pain be regularly assessed and reported in both medical and nursing records. Aim: To provide a homogeneous form to get exhaustive clinical information in the clinical report according to Italian legislation. Methods: A board, including oncologists and pain therapists, designed a form to report the pain characteristics of cancer patients in Italy in clinical records. The form was voted on through a Delphi process among directors of 18 clinical oncology specialization schools in Italy to obtain agreement on its content. Results: A form useful for collecting and reporting comprehensive and homogeneous information on pain among oncologists in Italy was produced. Conclusion: The development of common strategies for pain management can be improved by using this tool.

Researching the level of agreement among experts on terms used to describe wounds: An international study.

Establishing a common language that allows univocal and objective communication in describing wounds and their healing is of utmost importance in defining the diagnostic hypothesis and proper wound management. To measure the level of agreement on the description of wounds, an international study was performed among experts of different professional backgrounds on several common terms used to describe ulcerative lesions. A panel of 27 wound care experts anonymously completed a multiple-choice questionnaire on 100 images of 50 ulcerative lesions. The participants were asked to describe each image using a set of pre-defined terms. An expert data analyst interpreted the questionnaires to map the level of agreement on the used terminology. Our findings show a very low level of agreement among experts in using the proposed terminology to describe the wound bed, the wound edge, and the surrounding skin conditions. Efforts should be planned to find a consensus on the correct use of terminology for wound description. To this aim, partnership, consensus, and agreement with educators in medicine and nursing are necessary.

Reply to Lissing et al. Comment on "Ramai et al. Risk of Hepatocellular Carcinoma in Patients with Porphyria: A Systematic Review. Cancers 2022, 14, 2947".

We thank Dr. Lissing and colleagues for providing us with these helpful comments [...].

Understanding the Drawbacks of the Current Tumor Staging Systems: How to Improve?

Tumor stage definition is required for the description of the diagnosis and the development and use of treatment guidelines, as well as to enable clinical research (including clinical trials) and cancer surveillance [...].

Modulation of the Circulating Extracellular Vesicles in Response to Different Exercise Regimens and Study of Their Inflammatory Effects.

Exercise-released extracellular vesicles (EVs) are emerging as a novel class of exerkines that promotes systemic beneficial effects. However, slight differences in the applied exercise protocols in terms of mode, intensity and duration, as well as the need for standardized protocols for EV isolation, make the comparison of the studies in the literature extremely difficult. This work aims to investigate the EV amount and EV-associated miRNAs released in circulation in response to different physical exercise regimens. Healthy individuals were subjected to different exercise protocols: acute aerobic exercise (AAE) and training (AT), acute maximal aerobic exercise (AMAE) and altitude aerobic training (AAT). We found a tendency for total EVs to increase in the sedentary condition compared to trained participants following AAE. Moreover, the cytofluorimetric analysis showed an increase in CD81+/SGCA+/CD45- EVs in response to AAE. Although a single bout of moderate/maximal exercise did not impact the total EV number, EV-miRNA levels were affected as a result. In detail, EV-associated miR-206, miR-133b and miR-146a were upregulated following AAE, and this trend appeared intensity-dependent. Finally, THP-1 macrophage treatment with exercise-derived EVs induced an increase of the mRNAs encoding for IL-1ß, IL-6 and CD163 using baseline and immediately post-exercise EVs. Still, 1 h post-exercise EVs failed to stimulate a pro-inflammatory program. In conclusion, the reported data provide a better understanding of the release of circulating EVs and their role as mediators of the inflammatory processes associated with exercise.

Role of Etiology in Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Counterfactual Event-Based Mediation Analysis.

Background: Whether the etiology of underlying liver disease represents a prognostic factor in patients with hepatocellular carcinoma (HCC) treated with lenvatinib is still a matter of debate. This study investigates whether the viral etiology of HCC plays a prognostic role in overall survival (OS). Methods: Data derived from a multicenter series of 313 HCC patients treated with lenvatinib between 2019 and 2022 were analyzed. Actuarial survival estimates were computed using the Kaplan−Meier method and compared with the log-rank test. We performed an event-based counterfactual mediation analysis to estimate direct (chronic inflammation and immunosuppression), indirect (tobacco smoking, alcohol use, illicit drug abuse with injections), and the total effect of viral etiology on OS. Results were expressed as hazard ratio (HR) and 95% CI. Results: Median OS was 21 months (95% CI: 20−23) in the group with other etiologies and 15 months (14−16) in the group with viral etiology (p < 0.0001). The total effect of viral etiology was associated with OS (HR 2.76, 1.32−5.21), and it was mainly explained by the pure direct effect of viral etiology (HR 2.74, 1.15−4.45). By contrast, its total indirect effect was not associated with poorer survival (HR 1.05, 0.82−2.13). These results were confirmed when considering tobacco, alcohol consumption, or injection drug abuse as potential mediators. Median progression-free survival was 9 months (8−10) in patients with other etiologies and 6 months (5−7) in patients with viral etiology (p < 0.0001). No difference in terms of adverse event rate was observed between the two groups. Conclusions: Patients affected by HCC with nonviral etiology treated with lenvatinib exhibit longer survival than those with viral etiology. This finding may have relevance in the treatment decision-making process.

A Prospective Study Evaluating Health-Related Quality of Life Following a Multimodal Treatment for Colorectal Cancer.

PURPOSE: The major improvements in the diagnosis and treatment of colorectal cancer (CRC) over the past decades increased the patients' survival rates. Despite this, patients and clinicians still need to address the long-term physical and psychosocial effects over time. This paper aims to prospectively assess CRC patients' HR-QoL psychological distress and sexual functioning and identify clinical, demographic, and psychological predictors. METHODS: In total, 55 patients were evaluated from diagnosis to 5-year follow-up with the following instruments: EORTC QLQ-C30 and QLQ-C38 for QoL and sexuality; HADS for psychological distress; and specific questions to detect psychological variables. RESULTS: QoL worsened after diagnosis and returned to baseline values after 5 years. Sexual function significantly deteriorated over time (with no recovery, especially in women), while borderline/severe anxiety and depression decreased. A better HR-QoL at baseline was associated with better physical, social and sexual functioning, positive body image and sexual pleasure after 5 years. CONCLUSION: HR-QoL allows the early detection of patients at risk, favoring prompt patient-centered interventions.

Risk of Hepatocellular Carcinoma in Patients with Porphyria: A Systematic Review.

Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy. Porphyrias are inborn defects in the heme biosynthesis pathway resulting in neurovisceral manifestations and cutaneous photosensitivity attacks with multi-systemic involvement. Its estimated prevalence nears 5 per 100,000 patients worldwide. Subclinical liver disease is common, which can progress into transaminitis, fibrosis, cirrhosis, and malignancy. However, data on the incidence of primary liver cancer are lacking. We aim to determine the risk of hepatocellular carcinoma (HCC) in patients with porphyria. A systematic review and pooled analysis were conducted through 2021 on studies assessing blood tests, imaging, cancer development, liver transplant, surgical resection, and outcomes in porphyria. In total, 19 studies, which included 7381 patients with porphyria (3476 females), were considered for the final review. In eight studies, alpha-fetoprotein levels were elevated between 200 and 1000 IU/mL. Of the total cohort of patients with porphyria, primary liver cancer was diagnosed in 351 patients (4.8%), of whom 243 (3.3% of the total) were found to have HCC. A subset of patients was found to have cholangiocarcinoma (n = 18; 0.3% of the total). Interestingly, advanced liver disease or cirrhosis was not a prerequisite for the formation of HCC in a small group of patients. Of the total cohort, 30 patients underwent liver resection, 48 patients underwent liver transplantation, and 327 patients died. Patients with porphyria are at risk of developing primary liver malignancy. Further studies should aim to develop diagnostic and prognostic models aimed at the early detection of HCC in porphyria.