Search

Background: Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized. Objectives: In this study, we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by reviewing the available data and analyzing them by meta-analysis. Methods: We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction. A total of 8 retrospective, non-randomized, cohort studies were included in this meta-analysis, for a total of 1,071 Child-Pugh A and 225 Child-Pugh B patients. The albumin-bilirubin (ALBI) grade was also used to assess liver function, when available. Results: Grade ≥3 adverse events were observed in 11.8% of Child-Pugh class A and 26.8% class B patients (p = 0.0001), with an odds ratio (OR) of 0.43 (confidence interval [CI] 0.21–0.90; p = 0.02). Progression-free survival (PFS) at both 6 months (4.90 ± 2.08 vs. 4.75 ± 2.08 months; p = 0.0004) and 12 months (8.83 ± 2.32 vs. 7.26 ± 2.33 months; p = 0.002) was lower in Child-Pugh class B patients. A trend toward a higher objective response rate (ORR) was observed in Child-Pugh class A patients (219/856, 25.6%) as compared to Child-Pugh class B patients (25/138, 18.1%; p = 0.070), while the probability of obtaining an ORR was significantly greater in Child-Pugh A patients (OR 1.79, CI 1.12–2.86; p = 0.02). Median overall survival (OS) was 16.8 ± 2.0 and 6.8 ± 3.2 months in Child-Pugh A and B patients, respectively (mean difference 9.06 months, CI 7.01–11.1, p < 0.0001). Lastly, OS was longer in patients with ALBI grades 1–2 than in those with grade 3 (8.3 ± 11.4 vs. 3.3 ± 5.0 months, p = 0.0008). Conclusions: Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter PFS and OS associated with the greater likelihood of experiencing treatment-related adverse events observed in these patients suggest great caution and individualization of treatment, possibly with the support of the ALBI grade.

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 & Aims: HIV-seropositivity shortens survival in patients with hepatocellular carcinoma (HCC). Although risk factors for HCC including HCV infection can influence T cell phenotype, it is unknown whether HIV can influence functional characteristics of the T cell infiltrate. Methods: From the Liver Cancer in HIV biorepository, we derived 129 samples of transplanted (76%) or resected (20%) HCC in eight European and North American centres. We profiled intra- and peritumoural tissue to evaluate regulatory CD4+/FOXP3+ and immune-exhausted CD8+/PD1+ T cells in HIV+ (n = 66) and HIV- (n = 63) samples. We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples evaluated in relationship with HIV status. We correlated immunopathologic features with patients’ characteristics including markers of HIV infection. Results: Of the 66 HIV+ patients, 83% were HCV coinfected with an undetectable HIV viral load (51%) and a median blood CD4+ cell count of 430 cells/mm3 (range 15–908). Patients who were HIV+ were compared with HIV- controls with similar staging characteristics including Barcelona Clinic Liver Cancer (BCLC) stage A–B (86% vs. 83%, p = 0.16),

Obeticholic acid (OCA) improves cholestasis and is generally well tolerated in patients with primary biliary cholangitis (PBC) not responding, or intolerant, to ursodeoxycholic acid (UDCA). As PBC is mainly a cholestatic disorder, less attention is paid to aminotransferase behavior in the course of treatment. In this study we evaluated, in clinical practice, the efficacy of OCA treatment on both alkaline phosphatase (ALP) and alanine aminotransferase (ALT) using updated healthy ranges for aminotransferases. Fifteen PBC patients, non-responders to UDCA, were evaluated at baseline and during OCA treatment with serial measurement of cholestasis indexes and ALT, that were also assessed using updated normal ranges (p = 0.003) and from 0.93 to 0.78 × upper limit of normal (p = 0.008), respectively, in the course of OCA treatment. At treatment day-15, median ALT decreased by 29.7% and ALP by 8.8%. Bilirubin and albumin were unmodified throughout treatment. Using updated normal ranges, ALT levels were normal in 6.7% of patients at baseline and in 33.3% of patients at 18 months of treatment. OCA treatment improves cholestasis and, also, indexes of hepatocyte necrosis, with a decline in necro-inflammatory activity even predating the improvement in cholestasis. Use of recalibrated healthy ranges for aminotransferases might be a useful tool to assess hepatic histological activity and its improvement with OCA treatment.

Introduction: Community hospitals (CHs) could address the emerging complex care needs of patients. We investigated which characteristics of patients’ and CHs affect patient outcomes, in order to identify who could benefit the most from CH care and the best skill mix to deliver this care. Methods: We analysed all elderly patients discharged from the CHs of Emilia-Romagna, Italy. CH skill mix and care processes were collected with an ad hoc survey. The primary outcome was improvement in the Barthel index (BI) on discharge. Hierarchical regression analysis was performed to test the associations under study. Results: 53% of the patients had a BI improvement ≥10. After adjusting for the diverse case mix of the patients, no significant association was found between CH characteristics and BI improvement. Patient characteristics explained only a portion of the variability in CH performance. Discussion: Heterogeneity in case mix reflects the nature of CHs, which play context-specific roles as integrators between primary care services and hospitals. Residual variability in BI improvement rates across CHs might be attributed to aspects of care not detected in our survey. Conclusions: More research is needed to study the impact of CH skill mix and care processes on patient outcomes.

BACKGROUND: Caesarean delivery (CD) rates have been frequently used as quality measures for maternity service comparisons. More recently, primary CD rates (CD in women without previous CD) or CD rates within selected categories such as nulliparous, term, cephalic singleton deliveries (NTCS) have been used. The objective of this study is to determine the extent to which risk adjustment for clinical and socio-demographic variables is needed for inter-hospital comparisons of CD rates in women without previous CD and in NTCS deliveries. METHODS: Hospital discharge records of women who delivered in Emilia-Romagna Region (Italy) from January, 2007 to June 2009 and in Tuscany Region for year 2009 were linked with birth certificates. Adjusted RRs of CD in women without a previous Caesarean and NTCS were estimated using Poisson regression. Percentage differences in RR before and after adjustment were calculated and hospital rankings, based on crude and adjusted RRs, were examined. RESULTS: Adjusted RR differed substantially from crude RR in women without a previous Caesarean and only marginally in NTCS group. Hospital ranking was markedly affected by adjustment in women without a previous CD, but less in NTCS. CONCLUSION: Risk adjustment is warranted for inter-hospital comparisons of primary CD rates but not for NTCS CD rates. Crude NTCS CD rates are a reliable estimate of adjusted NTCS CD.

Abstract During tissue development, gradients of secreted signaling molecules known as morphogens provide cells with positional information. The mechanisms underlying morphogen spreading have been widely studied, however, it remains largely unexplored whether the shape of morphogen gradients is influenced by tissue morphology. Here, we developed an analysis pipeline to quantify the distribution of proteins within a curved tissue. We applied it to the Hedgehog morphogen gradient in the Drosophila wing and eye-antennal imaginal discs, which are flat and curved tissues, respectively. Despite a different expression profile, the slope of the Hedgehog gradient was comparable between the two tissues. Moreover, inducing ectopic folds in wing imaginal discs did not affect the slope of the Hedgehog gradient. Suppressing curvature in the eye-antennal imaginal disc also did not alter the Hedgehog gradient slope but led to ectopic Hedgehog expression. In conclusion, through the development of an analysis pipeline that allows quantifying protein distribution in curved tissues, we show that the Hedgehog gradient is robust towards variations in tissue morphology.