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Abstract Background Patient heterogeneity poses significant challenges for managing individuals and designing clinical trials, especially in complex diseases. Existing classifications rely on outcome-predicting scores, potentially overlooking crucial elements contributing to heterogeneity without necessarily impacting prognosis. Methods To address patient heterogeneity, we developed ClustALL, a computational pipeline that simultaneously faces diverse clinical data challenges like mixed types, missing values, and collinearity. ClustALL enables the unsupervised identification of patient stratifications while filtering for stratifications that are robust against minor variations in the population (population-based) and against limited adjustments in the algorithm’s parameters (parameter-based). Results Applied to a European cohort of patients with acutely decompensated cirrhosis (n = 766), ClustALL identified five robust stratifications, using only data at hospital admission. All stratifications included markers of impaired liver function and number of organ dysfunction or failure, and most included precipitating events. When focusing on one of these stratifications, patients were categorized into three clusters characterized by typical clinical features; notably, the 3-cluster stratification showed a prognostic value. Re-assessment of patient stratification during follow-up delineated patients’ outcomes, with further improvement of the prognostic value of the stratification. We validated these findings in an independent prospective multicentre cohort of patients from Latin America (n = 580). Conclusions By applying ClustALL to patients with acutely decompensated cirrhosis, we identified three patient clusters. Following these clusters over time offers insights that could guide future clinical trial design. ClustALL is a novel and robust stratification method capable of addressing the multiple challenges of patient stratification in most complex diseases.

Abstract Background Patient and public involvement (PPI) has become an essential part of health research. There is a need for genuine involvement in order to ensure that research is relevant to patients. This can then improve the quality, relevance, and impact of health research, while at the same time reducing wasted research and in doing so bringing science and society closer together. Despite the increasing attention for this involvement, it is not yet common practice to report on proposed activities. An article reporting planned PPI could provide guidance and inspiration for the wider academic community in future activities. Therefore, this current article aims to describe the way in which PPI principles are incorporated in the research project called “Quality of Life in Oncology: measuring what matters for cancer patients and survivors in Europe (EUonQoL).” This project aims to develop a new set of questionnaires to enable cancer patients to assess their quality of life, entitled the EUonQoL-Kit. Methods The first step is to recruit cancer patients and their informal caregivers as co-researchers in order to train them to collaborate with the researchers. Based on their skills and preferences, they are then assigned to several of the project’s work packages. Their individual roles, tasks, and responsibilities regarding the work packages, to which they have been assigned, are evaluated and adapted when necessary. The impact of their involvement is evaluated by both the researchers and co-researchers. Discussion PPI is a complex and dynamic process. As such, the overall structure of the research may be defined while at the same time leaving room for certain aspects to be filled in later. Our research is, we believe, relevant as co-researcher involvement in such a large European project as EUonQoL is a new development.

Abstract Background The decision to administer palliative radiotherapy (RT) to patients with bone metastases (BMs), as well as the selection of treatment protocols (dose, fractionation), requires an accurate assessment of survival expectancy. In this study, we aimed to develop three predictive models (PMs) to estimate short‐, intermediate‐, and long‐term overall survival (OS) for patients in this clinical setting. Materials and Methods This study constitutes a sub‐analysis of the PRAIS trial, a longitudinal observational study collecting data from patients referred to participating centers to receive palliative RT for cancer‐induced bone pain. Our analysis encompassed 567 patients from the PRAIS trial database. The primary objectives were to ascertain the correlation between clinical and laboratory parameters with the OS rates at three distinct time points (short: 3 weeks; intermediate: 24 weeks; prolonged: 52 weeks) and to construct PMs for prognosis. We employed machine learning techniques, comprising the following steps: (i) identification of reliable prognostic variables and training; (ii) validation and testing of the model using the selected variables. The selection of variables was accomplished using the LASSO method (Least Absolute Shrinkage and Selection Operator). The model performance was assessed using receiver operator characteristic curves (ROC) and the area under the curve (AUC). Results Our analysis demonstrated a significant impact of clinical parameters (primary tumor site, presence of non‐bone metastases, steroids and opioid intake, food intake, and body mass index) and laboratory parameters (interleukin 8 [IL‐8], chloride levels, C‐reactive protein, white blood cell count, and lymphocyte count) on OS. Notably, different factors were associated with the different times for OS with only IL‐8 included both in the PMs for short‐ and long‐term OS. The AUC values for ROC curves for 3‐week, 24‐week, and 52‐week OS were 0.901, 0.767, and 0.806, respectively. Conclusions We successfully developed three PMs for OS based on easily accessible clinical and laboratory parameters for patients referred to palliative RT for painful BMs. While our findings are promising, it is important to recognize that this was an exploratory trial. The implementation of these tools into clinical practice warrants further investigation and confirmation through subsequent studies with separate databases.

Abstract The current treatment approach to patients with liver cirrhosis relies on the individual management of complications. Consequently, there is an unmet need for an overall therapeutic strategy for primary and secondary prevention of complications. The clinical potential of long‐term albumin infusions supported by recent clinical trials has expanded its indications and holds promise to transform the management and secondary prevention of cirrhosis‐related complications. This renewed interest in albumin comes with inherent controversies, compounding challenges and pressing need for rigorous evaluation of its clinical potential to capitalize on its therapeutic breakthroughs. Australia is among a few countries worldwide to adopt outpatient human albumin infusion. Here, we summarize currently available evidence of the potential benefits of human albumin for the management of multiple liver cirrhosis‐related complications and discuss key challenges for wide application of long‐term albumin administration strategy in Australian clinical practice. Australian Gastroenterological week (AGW), organised by the Gastroenterological Society of Australia (GESA), was held between 9‐11 September 2022. A panel of hepatologists, advanced liver nurses and one haematologist, were invited to a roundtable meeting to discuss the use of long‐term albumin infusions for liver cirrhosis. management in Australia. In this review, we summarise the proceedings of this meeting in context of the current literature.

The Chain of Custody (CoC) standard tracks the recycled content (RC) of products, in most cases using the Mass Balance model. This model freely allows the selection of allocation methods and timeframes for the RC evaluation. Our work opens a discussion on the potential effects of this freedom in the RC evaluation. Firstly, we defined the general model representing the viable allocation methods and timeframe, and secondly, we applied the model to a case study. The mass balance model simplifies the monitoring of RC and encourages companies to use recycled materials. However, we outline the need for actions on stricter RC calculation and reporting, for instance, by reducing the timeframe of mass balance calculation or promoting the controlled blending model, which guarantees the physical presence of RC in the product. The results provide a basis for policymakers to set requirements for RC evaluation.

Background Electronic patient-reported outcomes (ePROMs) enhance symptom management and patients’ engagement in palliative cancer care. However, integrating them into this setting brings challenges, including patients’ familiarity with technological devices and declining health status. Prioritizing the patient's acceptability and feasibility is crucial for their adoption. However, more knowledge is needed about patients’ perspectives on the adoption of ePROMs in the community, especially for home-based palliative care. Aim Explore patient viewpoints on utilizing ePROMs for symptom reporting in home-based oncology palliative care. Design A qualitative interpretative approach was used to evaluate patients’ points of view on using ePROMs in this specific care setting. Semistructured interviews were carried out. Data were analyzed using a reflexive thematic analysis. Setting/participants A total of 25 patients receiving oncological home palliative care from the advanced palliative care unit of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, were invited to participate. Twenty interviews were conducted, as five patients declined due to deteriorating health. Results Four themes were identified: (1) strategic value of ePROMs and subjective appreciation; (2) enhancing patient centeredness through ePROMs; (3) exploring and addressing concerns about the use of ePROMs and (4) intersecting factors influencing the efficacy of ePROMs Conclusion Despite initial reticence, home palliative care patients consider ePROMs as potentially valuable allies monitoring symptoms, enhancing their quality of life, and amplifying their voices on less explored aspects of care. Continuous dialog between healthcare professionals and patients is crucial for addressing patient skepticism about ePROMs and their impact on the human aspect of care.

Abstract. Introduction:. Better diagnosis and treatment of neuropathic cancer pain (NcP) remains an unmet clinical need. The EAPC/IASP algorithm was specifically designed for NcP diagnosis; yet, to date, there is no information on its application and accuracy. Objectives:. Our aim was to determine the accuracy of the EAPC/IASP algorithm compared with the Neuropathic Special Interest Group grading system (gold standard) and to describe patients' sensory profile with quantitative sensory testing (QST). Methods:. This is a cross-sectional observational study conducted in a palliative care and pain outpatient clinic. Patients with cancer pain intensity ≥3 (numerical rating scale 0–10) were eligible. The palliative care physician applied the EAPC/IASP algorithm as a grading system to diagnose probable or definite NcP, and an independent investigator applied the gold standard and performed the QST. Sensitivity and specificity of the EAPC/IASP algorithm were measured in comparison with the gold standard results. Kruskal–Wallis and unequal variance independent-samples t tests were used to compare the QST parameters in patients with and without NcP. Results:. Ninety-eight patients were enrolled from August 2020 to March 2023. Sensitivity and specificity for the EAPC/IASP algorithm were 85% (95% CI 70.2–94.3) and 98.3% (95% CI 90.8–100), respectively. Patients with NcP in contrast to patients without NcP showed cold hypoesthesia (P = 0.0032), warm hypoesthesia (P = 0.0018), pressure hyperalgesia (P = 0.02), and the presence of allodynia (P = 0.0001). Conclusion:. The results indicate a good performance of the EAPC/IASP algorithm in diagnosing NcP and the QST discriminated well between patients with and without NcP.

Abstract Aim Assessing the incidence of Medication Related Osteonecrosis of the Jaw (MRONJ) in cancer patients with bone metastases receiving Denosumab (Dmab) and identifying potential risk factors. Methods A retrospective observational study on consecutive cancer patients with bone metastases, who received at least one dose of Dmab and one follow‐up visit. MRONJ crude cumulative incidence (CCI) was estimated considering death without MRONJ as competing event. Multiple regression models were used to study the association between MRONJ incidence and potential risk factors: age, cancer diagnosis, previous bisphosphonates, dental treatments before starting Dmab, extraction or other dental treatment during Dmab, chemotherapy, hormone therapy, and antiangiogenic (AA) agents concurrent use. Results On 780 patients included (median follow‐up 17 months), 54% and 18% had, respectively, breast and prostate cancer. The mean number of Dmab administration was 12. Fifty‐six patients developed MRONJ with a 24‐ and a 48‐month crude cumulative incidence of 5.7% (95% Cl: 4.2%–7.8%) and 9.8% (95% CI: 7.6%–12.7%), respectively. Higher MRONJ incidence was significantly associated with middle aged group (>56 and ≤73), both at univariate and multivariate analysis (p = 0.029 and 0.0106). Dental treatments (Hazard Ratio [HR] = 3.67; p = 0.0001), dental extractions (HR = 23.40; p

Abstract Background Patient-reported outcomes in palliative care enable early monitoring and management of symptoms that most impact patients’ daily lives; however, there are several barriers to adopting electronic Patient-reported Outcome Measures (e-PROMs) in daily practice. This study explored the experiences of health care professionals (HCPs) regarding potential barriers and facilitators in implementing e-PROMs in palliative cancer care at home. Methods This was a qualitative descriptive study. The data were collected from two focus groups structured according to the conceptual framework of Grol. HCPs involved in home palliative cancer care of Fondazione IRCCS Istituto Nazionale dei Tumori of Milan were enrolled. Data were analyzed using a reflexive thematic analysis. Results A total of 245 codes were generated, 171 for the first focus group and 74 for the second focus group. The results were subdivided into subthemes according to Grol’s themes: Innovation, Individual professional, Patient, Social context, Organizational context, except Economic Political context. Nine HCPs attended the first focus group, and ten attended the second. According to these participants, e-PROMs could be integrated into clinical practice after adequate training and support of HCPs at all stages of implementation. They identified barriers, especially in the social and organizational contexts, due to the uniqueness of the oncological end-of-life setting and the intangible care interventions, as well as many facilitators for the innovation that these tools bring and for improved communication with the patient and the healthcare team. Conclusions e-PROMs are perceived by HCPs as adding value to patient care and their work; however, barriers remain especially related to the fragility of these patients, the adequacy of technological systems, lack of education, and the risk of low humanization of care.

Sara Alfieri,1,* Cinzia Brunelli,2,* Claudia Borreani,1 Giuseppe Capri,3 Martina Angi,4 Giulia V Bianchi,3 Silvia Lo Dico,2 Pierangelo Spada,5 Viviana Fusetti,2,6 Ernesto Zecca,2 Augusto Caraceni2,7 1Clinical Psychology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 2Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 3Medical Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 4General Oncology Surgery 4, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 5Nursing, Technicians and Rehabilitation Management Service (SITRA), Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 6Biomedicine and Prevention Department, University of Rome “Tor Vergata”, Rome, Italy; 7Department of Clinical and Community Sciences, Università degli Studi, Milan, Italy*These authors contributed equally to this workCorrespondence: Cinzia Brunelli, Palliative Care, Pain Therapy and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, Milan, 20133, Italy, Tel +39 0223903179, Email cinzia.brunelli@istitutotumori.mi.itBackground: The multidisciplinary approach is considered “best practice” in oncology. Multidisciplinary Teamwork (MDTW) can be broadly classified into Multidisciplinary Team Meetings (MDTM) and Multidisciplinary Cancer Clinics (MDCC; involving also patients), yet both models are heterogeneously implemented.Purpose: This study aims at describing the different MDTW implemented models in a Comprehensive Cancer Center.Methods: All clinical unit directors of the hospital were contacted to identify any MDTW activities the personnel of the unit were involved in. Structured interviews were carried out to collect MDTWs information, ie, type (MDTM vs MDCC), team composition, aims, disease phase, use of Patient Reported Outcome Measures (PROMs). Descriptive analyses and Social Network Analysis (SNA) were performed.Results: Among 38 structured interviews, 25 concerned MDTMs and 13 in MDCCs. Responders were mainly surgeons (35%) and oncologists (29%), 35% of them were team leaders. Teams were mostly composed of physicians only (64% in MDTMs, 69% in MDCCs). Case managers (8% and 31%), palliative care specialists (12% and 23%) and psychologists (20% and 31%) were involved to a lesser extent, mainly when dealing with advanced disease. MDTWs were mainly aimed at integrating the skills of the different specialists (respectively 72% for MDTMs and 64% for MDCCs) and offering the best overall patient care pathway (64%, 61.5%). MDTWs were directed at patients in both diagnostic (72%, 61.5%) and locally advanced/metastatic (32%, 38.4%) disease. PROMs were seldom used (24%, 23%). SNA shows a similar density in the two MDTWs, but in the MDCCs two nodes remain isolated (pathologists and radiologists).Conclusion: Despite a high number of MDTWs for advanced/metastatic disease, there is limited involvement of palliative care specialists, psychologists, and nurses.Keywords: case conferences, multidisciplinary cancer conferences, multidisciplinary visits, oncology, tumor board, tumor conferences

Gastrointestinal tract breast cancer (BC) metastases represent a rare event and generally originate from the lobular subtype. Duodenal involvement was rarely described in previous case series. Abdominal symptoms are extremely unspecific and misleading. Diagnosis is challenging, and it consists of a few mandatory steps from radiological examinations to histological and immunohistochemical analyses. Here, we presented the clinical case of a 54-year-old postmenopausal woman who was hospitalized for vomiting and jaundice, presenting increased level of liver enzymes and minimal main bile duct and choledocus dilatation at abdominal ultrasonography. She underwent breast-conserving surgery and axillary lymph node dissection for stage IIIB lobular BC, 5 years before. Metastatic infiltration of the duodenal bulb originating from lobular BC was proven histologically, through fine-needle aspiration during endoscopic ultrasonography. Treatment was established after multidisciplinary team evaluation, based on the clinical status and prognosis of the patient. Pancreaticoduodenectomy was performed, and final histological examination confirmed the secondary localization of lobular BC, infiltrating the duodenal and gastric wall, pancreas parenchyma, and surrounding tissues. No metastatic lymph nodes were found. After surgery, the patient underwent first line of adjuvant systemic treatment with fulvestrant and ribociclib. After a follow-up of 21 months, the patient was in good clinical condition, without signs of locoregional or distant recurrence. This report stressed on the importance of a tailored therapeutic approach. Although systemic therapy generally represents the preferred option, surgery should not be excluded if an oncological radical resection can be performed achieving acceptable locoregional disease control.

Abstract Background Early palliative care (PC) has shown beneficial effects for advanced cancer patients. However, it is still debated what criteria to use to identify patients for PC referral. Aim To document the initial steps of the development of the Palliative Care Referral System (PCRS), a tool to be used by oncologists in clinical practice. Methods A multiprofessional working group developed the PCRS based on the results of a scoping literature review on PC referral criteria. PCRS criteria were evaluated by experts via a nominal group technique (NGT). Descriptive statistics were used to summarize expert scores on relevance, appropriateness and perceived feasibility of the criteria proposed. Quotations of participants during the discussion were also reported. Results Sixteen studies, including PC referral criteria/tools, emerged from the scoping review. Severe symptoms, poor performance status, comorbidities and prognosis were the most commonly used criteria. The PCRS included nine major criteria and nine assessment methods; a scoring procedure was also proposed. Answers to the questionnaire during the NGT showed that five criteria reached full agreement on all items, while four did not, and were then discussed within the group. Participants agreed on the relevance of all criteria and on the appropriateness of methods proposed to assess most of them, while issues were raised about potential feasibility of the overall assessment of the PCRS in clinical practice. Conclusion The PCRS has been developed as an help for oncologists to timely identify patients for specialized PC referral. Since feasibility emerged as the main concern, implementation strategies have to be tested in subsequent studies.

Background & Aims: Alcohol abuse and metabolic disorders are leading causes of hepatocellular carcinoma (HCC) worldwide. Alcohol-related aetiology is associated with a worse prognosis compared with viral agents, because of the lower percentage of patients diagnosed with HCC under routine surveillance and a higher burden of comorbidity in alcohol abusers. This study aimed to describe the evolving clinical scenario of alcohol-related HCC over 15 years (2006–2020) in Italy. Methods: Data from the Italian Liver Cancer (ITA.LI.CA) registry were used: 1,391 patients were allocated to three groups based on the year of HCC diagnosis (2006–2010; 2011–2015; 2016–2020). Patient characteristics, HCC treatment, and overall survival were compared among groups. Survival predictors were also investigated. Results: Approximately 80% of alcohol-related HCCs were classified as cases of metabolic dysfunction-associated fatty liver disease. Throughout the quinquennia,

Background: Disability related to incurable cancer affects over a million Europeans each year and people with cancer rank loss of function among the most common unmet supportive care needs. Objectives: To test the clinical and cost-effectiveness of an integrated short-term palliative rehabilitation intervention, to optimise function and quality of life in people affected by incurable cancer. Design: This is a multinational, parallel group, randomised, controlled, assessor blind, superiority trial. Methods: The INSPIRE consortium brings together leaders in palliative care, oncology and rehabilitation from partner organisations across Europe, with complementary expertise in health service research, trials of complex interventions, mixed-method evaluations, statistics and economics. Partnership with leading European civil society organisations ensures citizen engagement and dissemination at the highest level. We will conduct a multinational randomised controlled trial across five European countries, recruiting participants to assess the effectiveness of palliative rehabilitation for people with incurable cancer on the primary outcome – quality of life – and secondary outcomes including disability, symptom burden and goal attainment. To support trial conduct and enhance analysis of trial data, we will also conduct: comparative analysis of current integration of rehabilitation across oncology and palliative care services; mixed-method evaluations of equity and inclusivity, processes and implementation for the intervention, at patient, health service and health system levels. Finally, we will conduct an evidence synthesis, incorporating INSPIRE findings, and a Delphi consensus to develop an international framework for palliative rehabilitation practice and policy, incorporating indicators, core interventions, outcomes and integration methods. Scientific contribution: If positive, the trial could produce a scalable and equitable intervention to improve function and quality of life in people with incurable cancer and reduce the burden of care for their families. It could also upskill the practitioners involved and motivate future research questions. The intervention could be adapted and integrated into different health systems using existing staff and services, with little or no additional cost.

Introduction It is estimated that of those who die in high-income countries, 69%–82% would benefit from palliative care with a high prevalence of advanced chronic conditions and limited life prognosis. A positive response to these challenges would consist of integrating the palliative approach into all healthcare settings, for patients with all types of advanced medical conditions, although poor clinician awareness and the difficulty of applying criteria to identify patients in need still pose significant barriers. The aim of this project is to investigate whether the combined use of the NECPAL CCOMS-ICO and Palliative Prognostic (PaP) Score tools offers valuable screening methods to identify patients suffering from advanced chronic disease with limited life prognosis and likely to need palliative care, such as cancer, chronic renal or chronic respiratory failure.Methods and analysis This multicentre prospective observational study includes three patient populations: 100 patients with cancer, 50 patients with chronic renal failure and 50 patients with chronic pulmonary failure. All patients will be treated and monitored according to local clinical practice, with no additional procedures/patient visits compared with routine clinical practice. The following data will be collected for each patient: demographic variables, NECPAL CCOMS-ICO questionnaire, PaP Score evaluation, Palliative Performance Scale, Edmonton Symptom Assessment System, Eastern Cooperative Oncology Group Performance Status and data concerning the underlying disease, in order to verify the correlation of the two tools (PaP and NECPAL CCOMS-ICO) with patient status and statistical analysis.Ethics and dissemination The study was approved by local ethics committees and written informed consent was obtained from the patient. Findings will be disseminated through typical academic routes including poster/paper presentations at national and international conferences and academic institutes, and through publication in peer-reviewed journals.

IntroductionHepatic encephalopathy (HE) affects the survival and quality of life of patients with cirrhosis. However, longitudinal data on the clinical course after hospitalization for HE are lacking. The aim was to estimate mortality and risk for hospital readmission of cirrhotic patients hospitalized for HE.MethodsWe prospectively enrolled 112 consecutive cirrhotic patients hospitalized for HE (HE group) at 25 Italian referral centers. A cohort of 256 patients hospitalized for decompensated cirrhosis without HE served as controls (no HE group). After hospitalization for HE, patients were followed-up for 12 months until death or liver transplant (LT).ResultsDuring follow-up, 34 patients (30.4%) died and 15 patients (13.4%) underwent LT in the HE group, while 60 patients (23.4%) died and 50 patients (19.5%) underwent LT in the no HE group. In the whole cohort, age (HR 1.03, 95% CI 1.01–1.06), HE (HR 1.67, 95% CI 1.08–2.56), ascites (HR 2.56, 95% CI 1.55–4.23), and sodium levels (HR 0.94, 95% CI 0.90–0.99) were significant risk factors for mortality. In the HE group, ascites (HR 5.07, 95% CI 1.39–18.49) and BMI (HR 0.86, 95% CI 0.75–0.98) were risk factors for mortality, and HE recurrence was the first cause of hospital readmission.ConclusionIn patients hospitalized for decompensated cirrhosis, HE is an independent risk factor for mortality and the most common cause of hospital readmission compared with other decompensation events. Patients hospitalized for HE should be evaluated as candidates for LT.

Background & Aims: Patients with decompensated cirrhosis present frequent hospitalisations with a relevant clinical and socio-economic impact. This study aims to characterise unscheduled readmissions up to 1-year follow-up and identify predictors of 30-day readmission after an index hospitalisation for acute decompensation (AD). Methods: We performed a secondary analysis of a prospectively collected cohort of patients admitted for AD. Laboratory and clinical data at admission and at discharge were collected. Timing and causes of unscheduled readmissions and mortality were recorded up to 1 year. Results: A total of 329 patients with AD were included in the analysis. Acute-on-chronic liver failure was diagnosed in 19% of patients at admission or developed in an additional 9% of patients during the index hospitalisation. During the 1-year follow-up, 182 patients (55%) were rehospitalised and 98 (30%) more than once. The most frequent causes of readmission were hepatic encephalopathy (36%), ascites (22%), and infection (21%). Cumulative incidence of readmission was 20% at 30 days, 39% at 90 days, and 63% at 1 year. Fifty-four patients were readmitted for emergent liver-related causes within 30 days. Early readmission was associated with a higher 1-year mortality (47 vs. 32%, p = 0.037). Multivariable Cox regression analysis showed that haemoglobin (Hb) ≤8.7 g/dl (hazard ratio 2.63 [95% CI 1.38–5.02], p = 0.003) and model for end-stage liver disease-sodium score (MELD-Na) >16 at discharge (hazard ratio 2.23 [95% CI 1.27–3.93], p = 0.005), were independent predictors of early readmission. In patients with MELD-Na >16 at discharge, the presence of Hb ≤8.7 g/dl doubles the risk of early rehospitalisation (44% vs. 22%, p = 0.02). Conclusion: Besides MELD-Na, a low Hb level (Hb ≤8.7 g/dl) at discharge emerged as a new risk factor for early readmission, contributing to identification of patients who require closer surveillance after discharge. Impact and Implications: Patients with decompensated cirrhosis face frequent hospitalisations. In the present study, type and causes of readmissions were analysed during 1-year follow-up in patients discharged after the index hospitalisation for an acute decompensation of the disease. Early (30-day) liver-related readmission was associated with higher 1-year mortality. The model for end-stage liver disease-sodium score and low haemoglobin at discharge were identified as independent risk factors for early readmissions. Haemoglobin emerged as a new easy-to-use parameter associated with early readmission warranting further investigation.

Patients with decompensated cirrhosis, particularly those with acute‐on‐chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE‐SAFETY randomized, double‐blind, placebo‐controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography–tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan–kynurenine and carnitine beta‐oxidation pathways. An ACLF‐specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan–kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.

Abstract Background Despite evidence of the positive impact of routine assessment of patient-reported outcome measures (PROMs), their systematic collection is not widely implemented in cancer care. Aim To assess the knowledge, use and attitudes of healthcare professionals (HCPs) towards PROMs and electronically collected PROMs (ePROMs) in clinical practice and research and to explore respondent-related factors associated with the above dimensions. Method An ad hoc developed online survey was administered to all HCPs employed in clinical activity in an Italian comprehensive cancer center. The survey investigated which PROMs were known and used, as well as HCPs’ opinions on the advantages and drawbacks of routine PROM assessment, including electronic assessment (ePROM). Linear and logistic regression models were used for association analyses. Results Five Hundred Eleven of nine hundred ninety-two invited HCPs (52%) provided analyzable responses. 68% were women, 46% were nurses and 42% physicians, and 52.5% had > 20 years seniority. The average number of PROMs known was six among 17 proposed. All proved to be under-used (

The article aims to show how, over the decades, the noble ideals underlying the technological revolution began in the last century have been betrayed. The peculiar characteristics of that system defined as ʿsurveillance capitalismʾ by Shoshana Zuboff are first described, and then the historical and cultural framework allowing it to establish itself is reconstructed. Next, the consequences on human beings, such as the lack of privacy and the restriction of fundamental rights and liberties, are analyzed and discussed. Finally, the phenomenon of mass surveillance conducted through digital tools is addressed from a political and juridical point of view. In this regard, the risks that this represents for democratic political systems and the consequent legislative response that the European Union is trying to give are debated. Finally, conclusions are drawn.

Introduction Early palliative care (PC) in the clinical pathway of advanced cancer patients improves symptom control, quality of life and has a positive impact on overall quality of care. At present, standardised criteria for appropriate referral for early PC in oncology care are lacking. The aim of this project is to develop a set of standardised referral criteria and procedures to implement appropriate early PC for advanced cancer patients (the palliative care referral system, PCRS) and test its impact on user perception of quality of care received, on patient quality of life and on the use of healthcare resources.Setting Selected oncology clinics and PC outpatient clinic.Methods and analysis A scoping literature review and an expert consultation through a nominal group technique will be used to revise existing referral tools and to develop a new one, the PCRS. 25 patients will be enrolled in a pilot study to assess feasibility of the implementation of PCRS; 10 interviews with patients and healthcare professionals will be carried out to evaluate applicability.A pretest–post-test quasiexperimental study involving 150 patients before implementation of the PCRS and 150 patients after implementation will be carried out.Patient satisfaction with care received, quality of life and use of resources, and caregiver satisfaction with care will also be assessed to explore the impact of the intervention.Ethics and dissemination Ethical approval for the study has been granted by the Institutional Review board of the Fondazione IRCCS Istituto Nazionale Tumori; approval reference INT201/19.Results will be disseminated through open access publications and through scientific communication presented at national and international conferences.Trial registration number NCT04936568.

Flaminia Coluzzi,1,2 Domenico Alvaro,3 Augusto Tommaso Caraceni,4 Walter Gianni,5 Franco Marinangeli,6 Giuseppe Massazza,7 Carmine Pinto,8 Giustino Varrassi,9 Fabio Lugoboni10 1Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, LT, Italy; 2Anesthesiology, Intensive Care, and Pain Medicine Unit, Sant’Andrea University Hospital, Rome, RM, Italy; 3Department of Translational and Precision Medicine, Gastroenterology Division, Sapienza University of Rome, Rome, RM, Italy; 4Palliative Care, Pain Therapy, and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, MI, Italy; 5Department of Internal Medicine and Geriatric Medicine, University Hospital Policlinico Umberto I, Rome, RM, Italy; 6Department of Anesthesiology, Pain Medicine, and Palliative care, University of L’Aquila, L’Aquila, AQ, Italy; 7Division of Physical Medicine and Rehabilitation, Department of Surgical Sciences, University of Turin and “Città della Salute e della Scienza” University Hospital, Torino, TO, Italy; 8Medical Oncology Unit, Clinical Cancer Center, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, RE, Italy; 9Fondazione Paolo Procacci, Rome, RM, Italy; 10Department of Medicine, Addiction Unit, University Hospital of Verona, Verona, VR, ItalyCorrespondence: Flaminia ColuzziDepartment of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Latina, Corso della Repubblica 79, Latina, LT, 04100, ItalyTel +39 06 33775673Email flaminia.coluzzi@uniroma1.itBackground: Opioid-induced constipation (OIC) remains an important clinical obstacle despite the availability of several guidelines and pharmacological options for its management. Here, we surveyed common practices and perceptions about OIC among physicians who prescribe opioids in Italy.Methods: The online survey included 26 questions about OIC. Responses were analyzed descriptively and aggregated by physician specialty.Results: A total of 501 physicians completed the survey. Most respondents (67%) did not feel adequately educated about OIC despite general consensus regarding interest in the topic. Overall, 62– 75% of physicians regularly evaluated intestinal function or OIC symptoms in patients receiving opioid therapy. The most common method for assessment was patient diary; few physicians used a validated instrument such as the Rome IV criteria. Psychiatrists and addiction specialists showed the lowest interest and poorest practices. Most respondents (78%) preferred macrogol prophylaxis followed by macrogol plus another laxative for first-line treatment of OIC symptoms. Peripheral-acting mu opioid receptor antagonists (PAMORAs) were not widely used among physicians; 61% had never prescribed a PAMORA for OIC.Conclusion: Our findings reveal important differences in clinical practice for OIC across physician specialties. Additional formative efforts are necessary to improve awareness about best practices in OIC.Keywords: chronic pain, opioid, opioid-induced constipation, peripherally acting mu opioid receptor antagonist

Introduction Several studies show that soft tissue sarcoma patients undergoing surgery may experience reduced functional outcome and quality of life compared to the average population. Aim The aim of this case report is to show how an interactive platform, BoboPro, could be used as a supplementary instrumentation in assessment and treatment of balance and proprioceptive de cits. Materials and methods The patient had a mixoid liposacoma of the posterior compartment of the thigh and underwent a surgical resection of part of the sartorius, gracilis, semimembranosus muscles and semitendinosus muscle tendon. Three months after surgery he was assessed by our rehabilitation service. After evaluation through physical examination, validated scales and the interactive platform BoboPro with static and dynamic tests, he was found to have limited range of motion of knee and mild disturbance of double-leg stance balance and one-leg stance. Then the patient began a personalized rehabilitation treatment. At the end a new assessment was performed. Results After the rehabilitation treatment the patient showed an improvement in articularity and strenght of the lower limb treated with surgery. In the BoboPro system tests there was an improvement of about 30% in terms of accuracy in keeping the double-leg stance and of about 15% in the left-leg stance. Conclusion The peculiarity of our case is that BoboProallowed to point out a mild balance de cit and its improvement after rehabilitation exercise, even if it is not a standardized system. Its intuitive graphic feedback contributed to improve the patient’s compliance. This case report shows that BoboPro is an interesting tool as far as practicity and versatility is concerned.

Purpose AIOM guidelines aimed to provide evidence-based answers to practical questions concerning the effects of PA on the health demands of long-term cancer survivors. If regular PA should be recommended to these patients, the best proposal of PA, the recommendation of PA in lung cancer survivors and the safety of the prescription was investigated. Methods A systematic search was conduct on PUBMED and Cochrane database for meta- analyses, systemic reviews and primary studies (later updated 01/25/2019). The study selection criteria were population (long-term cancer survivors and non-metastatic off-therapy cancer survivors), PA intervention (aerobic exercise, resistance exercise and/or a combination of both, exercise of mild, moderate and vigorous intensity) and outcomes (overall mortality, cancer-speci c mortality, disease recovery, quality of life, “fatigue”, physical tness, reduction of treatment sequelae). The question on lung cancer survivors was studied with a dedicated research, updated on 01/23/2019 on MEDLINE/EMBASE/Central. Results In reviewing 32 report comprising large epidemiological trials, meta-analyses, systemic reviews, guidelines, randomized controlled trials with a total of several thousand study participants, we found that the PA brings important health bene ts for long-term cancer survivors. The Panel provides a strong recommendation to regular exercise at the same “dose” as the general population or adapted to comorbidities or cancer sequelae. Also recommends that all patients undergo a “multidimensional” assessment prior to PA prescription. The lack of speci c evidences in literature motivated the weak positive indication to PA in lung cancer survivors. Conclusions PA improves signi cantly the quality of life, depression, anxiety, “fatigue” and physical tness in long-term cancer survivors. And it is possible that it reduces the risk of overall, cancer-speci c mortality and disease recurrence. More research is needed to provide the best answers to cancer survivors' health questions: it is also hoped that clinicians, health-care professionals, people and authorities will increasingly pay attention to the needs of the long-term cancer population.

Stefano De Santis,1 Maria Domenica Simone,2 Sebastiano Mercadante,3 Rocco Domenico Mediati,4 Renato Vellucci,4 Paolo Marchetti,5 Giuseppe Tonini,6 Arturo Cuomo,7 Augusto Caraceni,8 Silvia Natoli,9 Grazia Armento,6 Livio Blasi,10 Massimo Mammucari11 On behalf of the IOPS-MS Study Group1Palliative Care and Oncologic Pain Service, S. Camillo-Forlanini Hospital, Rome, Italy; 2Hematology and BMT Unit, S. Camillo-Forlanini Hospital, Rome, Italy; 3Anesthesia and Intensive Care & Pain Relief and Supportive Care, La Maddalena, Palermo, Italy; 4Palliative Care and Pain Therapy Unit, Careggi Hospital, Florence, Italy; 5Molecular and Clinical Medicine Medical Oncology, La Sapienza University of Rome, Rome, Italy; 6Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy; 7Anesthesiology, Resuscitation, and Pain Therapy Department, National Cancer Institute, IRCCS Foundation, Naples, Italy; 8Palliative Care, Pain Therapy and Rehabilitation, National Cancer Institute, IRCCS Foundation, Milan, Italy; 9Department of Clinical Science and Translational Medicine – University of Rome Tor Vergata and Department of Emergency, Admission and Critical Area – Policlinic of Tor Vergata, Rome, Italy; 10Medical Oncology Unit, ARNAS Ospedale Civico Di Cristina Benfratelli, Palermo, Italy; 11Primary Care Unit, ASL RM1, Rome, 00165, ItalyCorrespondence: Stefano De Santis Email sdesantis@scamilloforlanini.rm.itBackground: International guidelines recommend moderate-to-severe cancer pain to be treated with strong opioids. However, pain management remains an unsolved matter, at least in the demanding oncology and palliative care setting. Although cancer pain consists of multiple components, which interact in complex ways where combination therapy can better intercept multiple pain characteristics, few studies have used a non-opioid/opioid association to exploit possible synergistic actions. Even the efforts of a recent approach emphasizing appropriate pain assessment and accurate classification to obtain personalized pain management have not produced a satisfactory analgesic strategy.Objective: This analysis was intended to evaluate the effectiveness of the immediate release fixed combination of oxycodone/acetaminophen (OxyIR/Par) for the treatment of moderate-to-severe intensity background pain used alone or in combination with other strong opioids in cancer patients with breakthrough cancer pain (BTcP). This is a secondary analysis of a wider observational, prospective, multicenter study [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] performed on 179 patients treated with opioids for cancer pain who received the fixed combination of oxycodone/acetaminophen (OxyIR/Par) for the treatment of background pain (BGP).Results: Cancer patients with breakthrough cancer pain and controlled BGP (Background Pain) were classified according to the presence of analgesic therapy with tablets of fixed combination OxyIR/Par alone (group A, n=120) or tablets of fixed combination OxyIR/Par combined with other strong opioids (group B, n=59). Clinical features of group A were different to group B: higher mean Karnofsky Performance Status Index 70.3% (95% CI=67.2– 73.5; median=70, CI=60– 80) vs 58.3 (95% CI=53.4– 63.2; median=50, CI=45– 70) (P< 0.001), and mainly group A patients were treated in an ambulatory setting (55.0% group A vs 33.9% group B) (p< 0.001). Both groups had managed BGP with similar mean dosages (group A: 12.0, CI=10.5– 13.4; group B: 13.1, CI=11.0– 15.1) and frequencies of OxyIR/Par alone for group A and in association to other opioids for group B, but Breakthrough cancer Pain (BTcP) exhibited different characteristics in the two groups, showing a lower mean intensity numerical rating scale (NRS) of 7.5 (95% CI=7.2– 7.7; median=7, CI=7– 8 group A) vs 7.9 (95% CI=7.6, 8.2; median= 8, CI=7– 9 group B) (P=0.04) and a higher percentage of patients had a faster onset, defined as the maximum intensity reached in less than 10 minutes, 81.7% (N=98) in group A vs 59.3% (n=35) in group B (P=0.002).Conclusion: This is the first analysis about the efficacy of an immediate-release fixed combination of OxyIR/Par in the real world for moderate-to-severe background cancer pain and breakthrough cancer pain. The oral fixed combination OxyIR/Par provided an adequate level of analgesia for moderate–severe background cancer pain, in a different cohort of cancer patients with different performance status, both in ambulatory and palliative settings. The low dosage of fixed combination OxyIR/Par was effective alone or in association with other opioids.Keywords: analgesia, combination of oxycodone/acetaminophen, cancer pain, breakthrough cancer pain

Abstract. Pain is highly prevalent in patients with cancer—nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid epidemics in some regions of the world, and limited opioid access in other regions have focused attention on nonopioid treatments. Given the limitations of monotherapy, combining nonopioids—such as antiepileptics and antidepressants—have shown promise in noncancer pain. This review seeks to evaluate efficacy of nonopioid combinations for cancer-related pain. Systematic searches of PubMed, EMBASE, and Cochrane CENTRAL were conducted for double-blind, randomized, controlled trials comparing a nonopioid combination with at least one of its components and/or placebo. This search yielded 4 randomized controlled trials, published between 1998 and 2019 involving studies of (1) imipramine + diclofenac; (2) mitoxantrone + prednisone + clodronate; (3) pentoxifylline + tocopherol + clodronate; and (4) duloxetine + pregabalin + opioid. In the first 3 of these trials, trends favouring combination efficacy failed to reach statistical significance. However, in the fourth trial, duloxetine + pregabalin + opioid was superior to pregabalin + opioid. This review illustrates recognition for the need to evaluate nonopioid drug combinations in cancer pain, although few trials have been published to date. Given the growing practice of prescribing more than 1 nonopioid for cancer pain and the need to expand the evidence base for rational combination therapy, more high-quality trials in this area are needed.