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Many hold that hospitalized elders rapidly undergo deconditioning because of enforced bedrest and inactivity that results in a significant decline in their ability to perform activities of daily living (ADL) and subsequent nursing home (NH) placement. The purpose of this study was to determine the differences in ADL functioning of NH residents admitted from an acute-care hospital with those admitted from other settings while controlling for other variables that can influence ADL functioning. A random sample of Missouri NH residents (n=10,000) was generated from statewide Minimum Data Set assessment data. The MDS-ADL Long Form Scale was used to calculation resident's ADL functioning and a backward elimination regression model was used. Findings indicate that after controlling for chronic health conditions, nutritional problems, physical capacity, cognitive status, and resident's belief about their ADL abilities that post-hospitalized elders have poorer ADL functioning than NH residents admitted from their own home or another NH.

In this study, the key exemplar processes of care in facilities with good resident outcomes were described. It follows that with description of these processes, it is feasible to teach facilities about the basics of care and the ways to systematically approach care so they can adopt these care processes and improve resident outcomes. However, for this to happen key organizational commitments must be in place for staff to consistently provide the basics of care. Nursing leadership must have a consistent presence over time, they must be champions of using team and group processes involving staff throughout the facility, and they must actively guide quality improvement processes. Administrative leadership must be present and express the expectation that high quality care is expected for residents, and that workers are expected to contribute to the quality improvement effort. If facilities are struggling with achieving average or poor resident outcomes, they must first make an effort to find nursing and administrative leaders who are willing to stay with the organization. These leaders must be skilled with team and group processes for decision-making and how to implement and use a quality improvement program to improve care. These leaders must be skilled at building employee relations and at retention strategies so residents are cared for by consistent staff who know them. The results of this study illustrate the simplicity of the basics of care that residents in nursing facilities need. The results also illustrate the complexity of the care processes and the organizational systems that must be in place to achieve good outcomes. Achieving these outcomes is the challenge facing those currently working in and leading nursing facilities. [ABSTRACT FROM AUTHOR]

Background and Aim: Less than 25 % of hepatocellular carcinoma (HCC) occurs in women, in whom prognosis could be better. Due to the lack of date in Europe, this study aims to assess survival of patients with HCC according sex in a tertiary French liver center., Patients and Methods: Every patient diagnosed with a first diagnosis of HCC presented at our weekly multidisciplinary tumor board between 2013 and 2017 were included. Baseline characteristics of patients and tumors were compared according sex using the Mann-Whitney test for Continuous variables and the Fisher or Chi-square test for dichotomous variables. Survival analyses according sex were conducted using the Kaplan-Meier method, the log-rank test, Cox models and a propensity score., Results: 694 patients were included, of whom 130 (18.7 %) were women. Among them, 587 (86 %) had cirrhosis, mainly compensated (Child A 62.7 %), and related to alcohol (48.7 %), HCV (27.2 %), and/or metabolic-associated fatty liver disease (25.8 %). HCC was unifocal in 54 % of cases, with a mean main nodule size of 37 mm. Curative treatment was administered in 45.4 % of cases (percutaneous ablation 93 %). Compared to men, women diagnosed with HCC were older (73 vs. 65 years, p < 0.001), were more frequently HCV-infected (40 % vs. 24 %, p = 0.0003) and presented more often with a solitary HCC (63 % vs. 52 %, p = 0.020). After a median follow-up of 57 months, overall survival was significantly longer in women both in multivariate analysis (aHR 1.39 (CI95 %: 1.07-1.81) p=0.014) and using a propensity score (HR 1.51 (1.13-2.02, p=0.005))., Conclusion: Despite being diagnosed at an older age, women with HCC exhibit significant better overall survival., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nathalie Ganne Carrie reports a relationship with Roche SAS that includes: consulting or advisory. Pierre Nahon reports a relationship with Roche SAS that includes: consulting or advisory. Pierre Nahon reports a relationship with Bristol Myers Squibb Co that includes: consulting or advisory. Pierre Nahon reports a relationship with MSD France SAS that includes: consulting or advisory. Pierre Nahon reports a relationship with AstraZeneca R&D that includes: consulting or advisory. Pierre Nahon reports a relationship with Ipsen that includes: consulting or advisory. Pierre Nahon reports a relationship with Eisai Inc that includes: consulting or advisory. Jean-Charles Nault reports a relationship with Ipsen that includes: funding grants. Jean-charles Nault reports a relationship with Bayer that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background & Aims: Safety data for patients with hepatocellular carcinoma (HCC) treated with atezolizumab-bevacizumab in the real-world setting remain uncertain. Thus, the aim of this study was to evaluate the incidence of adverse events (AEs) in patients with HCC treated with atezolizumab-bevacizumab in the literature., Methods: In this systematic review and meta-analysis, we searched PubMed for original studies reporting percentages of AEs in patients with HCC receiving atezolizumab-bevacizumab between 2020 to 2023, using the search terms "Atezolizumab/Bevacizumab", "HCC" and "Adverse events". We summarized the incidence of AEs and performed a meta-analysis in order to evaluate the incidence of AEs reported in the literature., Results: A total of 30 studies (3,867 patients) were included. The analysis revealed heterogeneity in AE reporting, with arterial hypertension, proteinuria, and fatigue being the most frequently reported AEs whereas incidence of bleeding was reported in 66.7% of the studies and rare immune-related AEs were reported in 26.7% of the studies. The meta-analysis revealed pooled incidence rates of 79% for any grade AEs: 56% for grade 1/2 and 30% for grade ≥3. While the pooled rates of hypertension, anorexia, bleeding, pruritus, rash, and thyroid dysfunction were similar to those reported in the IMbrave150 trial, higher rates were observed in the literature for proteinuria, fatigue, ALT and AST elevations and gastrointestinal perforation. For grade ≥3 AEs, the percentages were consistent with the IMbrave150 trial, except for lower incidences of arterial hypertension and thrombosis in the literature. The exposure-adjusted incidence rates for proteinuria (55.7%), hypertension (45.3%) and fatigue (33.6%) were high. Heterogeneity was observed in the analysis of AEs across articles within the same cohorts of patients., Conclusion: We observed a significant variability in AE reporting for atezolizumab-bevacizumab treatment in HCC in the literature, underscoring the need for standardized reporting practices., Impact and Implications: Considering the demonstrated safety of atezolizumab-bevacizumab in randomized-controlled trials, this meta-analysis offers valuable insights into reported occurrences of adverse events. Our study highlights significant heterogeneity among studies, underscoring the need to improve adverse event recording. Understanding the incidence and severity of treatment-related adverse events beyond clinical trials is essential for prompt intervention and may help in preventing treatment discontinuation and complications, potentially leading to better outcomes without significantly compromising quality of life due to adverse events., (© 2024 The Author(s).)

Introduction: The effectiveness of percutaneous radiofrequency ablation (RFA) in intrahepatic cholangiocarcinomas (iCCA) remains insufficiently studied., Methods: We conducted a retrospective study including patients with histologically proven iCCA within Milan criteria treated by percutaneous RFA from 2000 to 2022. The primary outcome was overall survival in treatment-naive patients and secondary outcomes included ablation completeness, adverse events, local and distant recurrence. A total of 494 patients with hepatocellular carcinoma (HCC) on cirrhosis treated by RFA were included as a comparison group. Oncological events were analysed using Kaplan-Meier, log-rank and univariate/multivariate Cox models., Results: The main population included 71 patients, mostly cirrhotic (80%) with solitary tumours (66%) of a median size of 24 mm. Local recurrence was 45% at 5 years, lower in multibipolar versus monopolar RFA (22% vs. 55%, p = .007). In treatment-naive patients (n = 45), median overall and recurrence-free survivals were 26 and 11 months, respectively. Tumour size (p = .01) and Child-Pugh B (p = .001) were associated with death. The rate of distant recurrence was 59% at 5 years significantly lower for single tumours of less than 2 (p = .002) or 3 cm (p = .02). In cirrhotic patients naïve of previous treatment (n = 40), overall survival was shorter than in HCC (26 vs 68 months, p < .0001), with more local recurrences (p < .0001). Among distant recurrences, 50% were extrahepatic metastases compared to 12% in HCC (p < .001)., Conclusion: Multibipolar RFA provides better results in terms of tumour recurrence than monopolar RFA and could be used to treat small iCCA (<3 cm). Adjuvant chemotherapy should be discussed due to the frequent extra-hepatic metastasis at recurrence., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: We aim to assess the long-term outcomes of percutaneous multi-bipolar radiofrequency (mbpRFA) as the first treatment for hepatocellular carcinoma (HCC) in transplant-eligible cirrhotic patients, followed by salvage transplantation for intrahepatic distant tumour recurrence or liver failure., Materials and Methods: We included transplant-eligible patients with cirrhosis and a first diagnosis of HCC within Milan criteria treated by upfront mbp RFA. Transplantability was defined by age <70 years, social support, absence of significant comorbidities, no active alcohol use and no recent extrahepatic cancer. Baseline variables were correlated with outcomes using the Kaplan-Meier and Cox models., Results: Among 435 patients with HCC, 172 were considered as transplantable with HCCs >2 cm (53%), uninodular (87%) and AFP >100 ng/mL (13%). Median overall survival was 87 months, with 75% of patients alive at 3 years, 61% at 5 years and 43% at 10 years. Age (p = .003) and MELD>10 (p = .01) were associated with the risk of death. Recurrence occurred in 118 patients within Milan criteria in 81% of cases. Local recurrence was observed in 24.5% of cases at 10 years and distant recurrence rates were observed in 69% at 10 years. After local recurrence, 69% of patients were still alive at 10 years. At the first tumour recurrence, 75 patients (65%) were considered transplantable. Forty-one patients underwent transplantation, mainly for distant intrahepatic tumour recurrence. The overall 5-year survival post-transplantation was 72%, with a tumour recurrence of 2.4%., Conclusion: Upfront multi-bipolar RFA for a first diagnosis of early HCC on cirrhosis coupled with salvage liver transplantation had a favourable intention-to-treat long-term prognosis, allowing for spare grafts., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: MET amplification ( MET amp) has been reported in 1%-5% of patients with hepatocellular carcinoma (HCC) and may be sensitive to MET inhibition. Tepotinib, a selective MET inhibitor, has shown promising activity in HCC with MET overexpression. We investigated the preclinical and clinical activity of tepotinib in HCC with MET amp ( MET gene copy number [GCN] ≥5), including high-level MET amp ( MET GCN ≥10)., Methods: Preclinical antitumor activity of tepotinib 100 mg/kg (orally, days 1-5, every 7 days, 3-5 weeks; 3-12 replicates) was evaluated according to MET amp status, as determined using the nCounter platform (NanoString), in 37 HCC patient-derived xenografts (PDXs) in immunodeficient mice. Clinical outcomes were evaluated in patients with MET amp by fluorescence in situ hybridization who received tepotinib 500 mg (450 mg active moiety) in two phase Ib/II trials in HCC with MET overexpression., Results: Across the PDX models, tepotinib induced complete or near-complete tumor regression in the only two models with high-level MET amp. Median tumor volume reductions were 100% and 99.8% in models with MET GCN 47.1 and 44.0, respectively. Across the two clinical trials, 15/121 patients had MET amp. Disease control was achieved by 11/15 patients with MET amp (complete response [CR], n = 1; partial response [PR], n = 4; stable disease [SD], n = 6) and 4/4 with high-level MET amp (CR, n = 1; PR, n = 2; SD, n = 1). All three patients with high-level MET amp and objective response received treatment for >1 year, including one patient who received first-line tepotinib for >6 years., Conclusion: High-level MET amp may be an oncogenic driver in HCC that is sensitive to MET inhibitors such as tepotinib.

Aggressive intrasegmental recurrence (AIR) is a form of local recurrence associated with a dismal prognosis and defined by multiple nodules or by an infiltrative mass with a tumor thrombus, occurring in the treated segment, after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to identify radiological and/or histological characteristics of tumor biopsy predictive of AIR. We retrospectively analyzed patients treated by No-Touch multi-bipolar RFA (mbpRFA) for a first HCC with a systematic per-procedural tumor biopsy positive for diagnosis of HCC. The first recurrence was classified as non-aggressive local recurrence, AIR or intrahepatic distant recurrence. 212 patients were included (168 men; mean age 67.1 years; mean tumor size 28.6 mm, 181 cirrhosis). AIR occurred in 21/212 patients (10%) and was associated with a higher risk of death (57% in patients with AIR vs 30% without AIR, p = 0.0001). Non-smooth tumor margins, observed in 21% of the patients and macro-trabecular massive histological subtype, observed in 12% of the patients were independently related to a higher risk of AIR (HR: 3.7[1.57;9.06], p = 0.002 and HR:3.8[2.47;10], p = 0.005 respectively). Non smooth margins at imaging and macro-trabecular massive histological subtype are associated with AIR and could be considered as aggressive features useful to stratify therapeutic strategy., (© 2022. The Author(s).)

Introduction: We aim to assess the outcomes of percutaneous ablation of locally advanced HCC in a tertiary center, which is usually not indicated. We compared to sorafenib or trans-arterial radioembolization (TARE)., Methods: We included 272 patients with HCC and tumor portal invasion treated by percutaneous ablation (n = 44) assessed retrospectively from one center compared to a control group from the SARAH trial including patients treated with sorafenib (n = 123) or TARE (n = 105). A propensity-score matching was performed in a subgroup of patients with similar baselines characteristics., Results: 84% of patients treated by ablation were male with a unique nodule (median size 50 mm) in 72.7% of the case. Complete tumor ablation was achieved in 75% of the patients with 20% Dindo-Clavien III-V adverse events including 6.8% of 90-days mortality. Sum of tumor size ≥70 mm was associated with incomplete ablation (p = 0.0239) and a higher risk of death (p = 0.0375). Patients in control group had a higher tumor burden, and more Vp3/4 compared to ablation group. Median overall survival was similar in the ablation and in the control group (16.4 and 14.0 months respectively, p = 0.48). The median progression-free survival was 6.6 months in ablation group compared to 4.2 months in the control group (p = 0.12)., Conclusion: Percutaneous ablation for locally advanced HCC was feasible and associated with similar long-term outcomes to sorafenib or TARE., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: This Phase 1b/2 study evaluated tepotinib, a highly selective MET inhibitor, in US/European patients with sorafenib pretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression., Methods: Eligible adults had aHCC, progression after ≥4 weeks of sorafenib, and, for Phase 2 only, MET overexpression. Tepotinib was administered once daily at 300 or 500 mg in Phase 1b ('3 + 3' design), and at the recommended Phase 2 dose (RP2D) in Phase 2. Primary endpoints were dose-liming toxicities (DLTs; Phase 1b) and 12-week investigator-assessed progression-free survival (PFS; Phase 2)., Results: In Phase 1b (n = 17), no DLTs occurred and the RP2D was confirmed as 500 mg. In Phase 2 (n = 49), the primary endpoint was met: 12-week PFS was 63.3% (90% CI: 50.5-74.7), which was significantly greater than the predefined null hypothesis of ≤15% (one-sided binomial exact test: P < 0.0001). Median time to progression was 4 months. In Phase 2, 28.6% of patients had treatment-related Grade ≥3 adverse events, including peripheral oedema and lipase increase (both 6.1%)., Conclusions: Tepotinib was generally well tolerated and the RP2D (500 mg) showed promising efficacy and, therefore, a positive benefit-risk balance in sorafenib pretreated aHCC with MET overexpression., Trial Registration: ClinicalTrials.gov: NCT02115373., (© 2021. The Author(s).)

Background: In Western countries, hepatocellular carcinoma (HCC) in hepatitis B (HBV) patients without cirrhosis was poorly studied. The aim was to describe the characteristics and outcome of HBV-related HCC according to fibrosis stage., Method: All patients with chronic HBV infection and HCC discussed in a multidisciplinary tumor board between 2007 and 2017 were retrospectively included., Results: A total of 152 out of 2,038 HCC patients had underlying HBV infection. HBV viral load>2000IU/ml, positive HBeAg and Hepatitis D coinfection were observed in 41%, 13% and 13% of cases, respectively. HCC was uninodular in 53%, associated with portal thrombosis in 16% and/or metastasis in 9% of cases. 130 patients (86%) had cirrhosis. No difference regarding HCC risk factors and viral characteristics was observed according to fibrosis stage. 5-year survival was 48%(47% on cirrhosis versus 57% without cirrhosis, P=0.26). At HCC diagnosis, 47% and 32% of cirrhotic and non-cirrhotic patients received an antiviral treatment (AVT), which was associated with less aggressive tumor and better survival (P=0.005). In cirrhosis, screening was associated with a lower tumor burden and patients were more amenable to curative treatment with better outcome (P<0.001)., Conclusion: HBV represents 8% of HCC etiologies without differences of viral characteristics according to fibrosis stage. AVT and surveillance were associated with less aggressive tumors, better access to curative treatment and outcome., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background and Aim: The prognostic value of transient elastography (TE) in cirrhotic patients with hepatocellular carcinoma (HCC) treated by percutaneous radiofrequency ablation (RFA) is currently unknown., Method(s): We included patients with histologically proven cirrhosis and with a first diagnosis of HCC inside Milan criteria treated by percutaneous RFA, and with TE available the year before treatment with 10 shots and interquartile range/median < 30%. Association between variables and clinical events was assessed by the Kaplan-Meier method with the log-rank test and using Cox univariate and multivariate analyses., Results: One hundred fifty-nine patients were included, with a median age of 65 years; 77.4% were men. Causes of cirrhosis were alcohol consumption (48.1%), hepatitis C (43.7%), hepatitis B (12.7%), and non-alcoholic steatohepatitis (32.3%). Median value of TE was 26 kPa (4-75 kPa). Overall survival at 1, 2, and 5 years was, respectively, 93%, 81%, and 44%; overall recurrence was 28%, 49%, and 80%. The TE value was not associated with tumor recurrence (0.13). In contrast, in univariate analysis, TE value, age, Child-Pugh B, and alkaline phosphatase were predictive factors in overall survival. In multivariate analysis, TE value (hazards ratio [HR] = 1.02, 95% confidence interval (IC): 1.01-1.04, 0.001), age (HR = 1.05, 95% IC: 1.03-1.08, P = 0.00006), and Child-Pugh B score (HR = 2.78, 95% IC: 1.27-6.08, P = 0.01) were independently associated with higher risk of death. A TE value ≥ 40 kPa was associated with shorter median overall survival (34 months) compared to a TE value < 40 kPa (59 months, P = 0.0008)., Conclusion(s): Transient elastography (TE) predicts overall survival but not tumor recurrence in cirrhotic patients with HCC treated by RFA., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Aims and Background: Only few patients with cirrhosis and hepatocellular carcinoma (HCC) larger than 5 cm are amenable to resection or straight liver transplantation, and in such circumstances, multibipolar radiofrequency ablation (mbp-RFA) could be a reliable alternative. This study was aimed to assess the long-term outcome in patients treated with mbp-RFA for unresectable HCC > 5 cm., Methods: Eighty-three consecutive patients with cirrhosis (median age 70 years [37-93 years], 67 males, BCLC A/B/C: 54/21/8, 74 naive) with up to three HCCs, the largest > 5 cm in diameter (median: 6.2 cm, 5.1-9 cm, 22 infiltrative forms, 12 with segmental portal invasion of which 10 were infiltrative forms) were treated with mbp-RFA. Overall (OS) and recurrence-free (RFS) survival and their associated predictive factors were assessed., Results: Complete ablation was observed in 78/83 (94%) patients. Thirty-one side effects occurred, including 6 (7%) severe complications. After a median follow-up of 26.1 months (1-112 months), in naive patients the 3- and 5-year OS was 51% (38-62) and 24% (13-36), 63 and 30% for mass-forming and 25 and 6% for infiltrative form, respectively. Infiltrative form (HR: 2.5 [1.33-4.69], p = 0.004) was the only independent OS predictor. In naive patients with mass-forming and infiltrative form, the 3- and 5-year RFS were 47 and 17 and 18 and 18%, respectively. Alpha-fetoprotein (HR: 2.86 [1.32-6.21], p = 0.008), multinodular form (HR: 2.74 [1.4-5.38], p = 0.003) and infiltrative form (HR: 3.43 [1.67-7.01], p = 0.0007) were independent RFS predictors., Conclusions: mbp-RFA offers good OS in inoperable patients with cirrhosis and large HCC, with acceptable safety profile. For infiltrative forms, although mbp-RFA leads to complete responses in more than 80% cases, few only remain tumor progression-free in long-term.

Background: We aimed to identify the main determinants of long-term overall survival (OS), including virologic control, and recurrence after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) on cirrhosis., Methods: Cirrhotic patients treated by RFA for HCC within Milan criteria were included. Associations between patient features and events were estimated by the Kaplan-Meier method with the log rank test and using uni/multivariate Cox models., Results: 389 cirrhotic patients (Child-Pugh A 86.6%, 473 tumors) were included. OS was 79.8%, 42.4% and 16%, and overall tumor recurrence 45%, 78% and 88% at 2, 5 and 10 years, respectively. In multivariate analysis, age, Child-Pugh, GGT, HCC near major vessels, esophageal varices, alkaline phosphatase and HBV predicted OS. Gender, ALT, AFP and alcohol intake were associated with tumor recurrence. Multinodular HCC (19.5%) was associated with risk of tumor recurrence outside Milan criteria. HBV patients had longer OS than other patients (P = 0.0059); negative HBV PCR at RFA was associated with decreased tumor recurrence (P = 0.0157). Using time-dependent analysis in HCV patients, a sustained virologic response was associated with increased OS (124.5 months) compared to other patients (49.2 months, P < 0.001)., Conclusion: Virologic response and severity of underlying liver disease were the main determinants of long-term OS after RFA for HCC developing on cirrhosis., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Prognostic biomarkers are needed in a heterogeneous population of patients with intermediate hepatocellular carcinoma (HCC) treated by transarterial (chemo)embolization. We aimed to validate the prognostic value of serum CRP levels and the STATE score, combining CRP, albumin and tumor burden., Methods: All cirrhotic patients with HCC treated by a first transarterial (chemo)embolization (2007-2013) in our institution were included. Overall survival was assessed using the Kaplan-Meier method, log rank, univariate and multivariate Cox analyses., Results: Among 157 patients included, 87% were men, 86% had Child Pugh A. Etiologies of liver disease included alcohol (57%), hepatitis C (32%), hepatitis B (11%) and/or metabolic syndrome (32%); 89% of patients were classified BCLC B. 33% of the patients had a CRP >1mg/dl and 33% a STATE score conferring poor prognosis (<18). Patients with CRP <1mg/dl had better overall survival than patients with CRP >1mg/dl (20 vs. 8 months, P=0.00186). Median overall survival was 6.73 months for patients with a STATE score <18 vs. 22.23 months for patients with STATE-score ≥18 (P=0.0002). In multivariate analysis, a STATE score <18 was independently associated with increased mortality (HR: 2.06 (CI95%: 1.28-3.34), P=0.0031)., Conclusion: In cirrhotic patients with HCC who underwent transarterial treatment, serum CRP level and STATE score at baseline can predict overall survival., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)